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Sample records for voltage-dependent gating strong

  1. Voltage-dependent gating of hERG potassium channels

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    Yen May eCheng

    2012-05-01

    Full Text Available The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4-S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-a-go-go related gene, hERG, which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure-function relationships underlying voltage-dependent gating in Shaker and hERG channels, with a focus on the roles of the voltage sensing domain and the S4-S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter charge interactions. More recent data suggest that key amino acid differences in the hERG voltage sensing unit and S4-S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor.

  2. Charged Residues at the First Transmembrane Region Contribute to the Voltage Dependence of the Slow Gate of Connexins.

    Science.gov (United States)

    Pinto, Bernardo I; García, Isaac E; Pupo, Amaury; Retamal, Mauricio A; Martínez, Agustín D; Latorre, Ramón; González, Carlos

    2016-07-22

    Connexins (Cxs) are a family of membrane-spanning proteins that form gap junction channels and hemichannels. Connexin-based channels exhibit two distinct voltage-dependent gating mechanisms termed slow and fast gating. Residues located at the C terminus of the first transmembrane segment (TM-1) are important structural components of the slow gate. Here, we determined the role of the charged residues at the end of TM-1 in voltage sensing in Cx26, Cx46, and Cx50. Conductance/voltage curves obtained from tail currents together with kinetics analysis reveal that the fast and slow gates of Cx26 involves the movement of two and four charges across the electric field, respectively. Primary sequence alignment of different Cxs shows the presence of well conserved glutamate residues in the C terminus of TM-1; only Cx26 contains a lysine in that position (lysine 41). Neutralization of lysine 41 in Cx26 increases the voltage dependence of the slow gate. Swapping of lysine 41 with glutamate 42 maintains the voltage dependence. In Cx46, neutralization of negative charges or addition of a positive charge in the Cx26 equivalent region reduced the slow gate voltage dependence. In Cx50, the addition of a glutamate in the same region decreased the voltage dependence, and the neutralization of a negative charge increased it. These results indicate that the charges at the end of TM-1 are part of the slow gate voltage sensor in Cxs. The fact that Cx42, which has no charge in this region, still presents voltage-dependent slow gating suggests that charges still unidentified also contribute to the slow gate voltage sensitivity.

  3. The Mechanism of Voltage Dependent Gating of the NaChBac Prokaryotic Sodium Channel

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    Decaen, Paul G.

    Electrical signaling in cells depends on selective conductance of ions through membrane proteins called 'voltage gated ion channels'. These channels are characterized by their ability turn on and off the flow of ionic current by opening and closing their conductive pore in response to changes in membrane potential. The opening and closing of the pore is a mechanically linked to conformational movement of the positively charged fourth transmembrane segment (S4) in 'the voltage sensor' region. How the S4 moves in response to membrane potential is a controversial subject. In this thesis, we used the prokaryotic sodium channel NaChBac as our model sodium channel to study voltage dependent movement of the S4 in the voltage sensor. We use a disulfide-locking method where we introduced pairs of cysteines in the voltage sensor that crosslink and trap the S4 in its path after depolarization. We screened over one hundred mutations of the NaChBac channel in the whole cell patch clamp assay and demonstrated discrete and sequential voltage dependent ion pair interactions that occur in at least three states between the positively charged residues of the S4 segment and the acidic residues in the S1, S2 and S3 segments. In conjunction with structural modeling of the voltage sensor and our disulfide locking data, we propose that the S4 moves in and out of the plane of the membrane 8-13 A, forming distinct gating charge interactions with counter charges of the voltage sensor and adopts a 310 helix over a portion of its structure during activation. These findings are compatible with the sliding helix model and refine our understanding of the structural determinates of voltage sensor function in voltage gated ion channels.

  4. PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid modulation of voltage-dependent gating

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    Mark Alan Zaydman

    2014-05-01

    Full Text Available Voltage-gated potassium (Kv channels contain voltage-sensing (VSD and pore-gate (PGD structural domains. During voltage-dependent gating, conformational changes in the two domains are coupled giving rise to voltage-dependent opening of the channel. In addition to membrane voltage, KCNQ (Kv7 channel opening requires the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2. Recent studies suggest that PIP2 serves as a cofactor to mediate VSD-PGD coupling in KCNQ1 channels. In this review, we put these findings in the context of the current understanding of voltage-dependent gating, lipid modulation of Kv channel activation, and PIP2-regulation of KCNQ channels. We suggest that lipid-mediated coupling of functional domains is a common mechanism among KCNQ channels that may be applicable to other Kv channels and membrane proteins.

  5. PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid modulation of voltage-dependent gating.

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    Zaydman, Mark A; Cui, Jianmin

    2014-01-01

    Voltage-gated potassium (Kv) channels contain voltage-sensing (VSD) and pore-gate (PGD) structural domains. During voltage-dependent gating, conformational changes in the two domains are coupled giving rise to voltage-dependent opening of the channel. In addition to membrane voltage, KCNQ (Kv7) channel opening requires the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2). Recent studies suggest that PIP2 serves as a cofactor to mediate VSD-PGD coupling in KCNQ1 channels. In this review, we put these findings in the context of the current understanding of voltage-dependent gating, lipid modulation of Kv channel activation, and PIP2-regulation of KCNQ channels. We suggest that lipid-mediated coupling of functional domains is a common mechanism among KCNQ channels that may be applicable to other Kv channels and membrane proteins.

  6. State-dependent FRET reports calcium- and voltage-dependent gating-ring motions in BK channels

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    Miranda, Pablo; Contreras, Jorge E.; Plested, Andrew J. R.; Sigworth, Fred J.; Holmgren, Miguel; Giraldez, Teresa

    2013-01-01

    Large-conductance voltage- and calcium-dependent potassium channels (BK, “Big K+”) are important controllers of cell excitability. In the BK channel, a large C-terminal intracellular region containing a “gating-ring” structure has been proposed to transduce Ca2+ binding into channel opening. Using patch-clamp fluorometry, we have investigated the calcium and voltage dependence of conformational changes of the gating-ring region of BK channels, while simultaneously monitoring channel conductan...

  7. The voltage dependence of GABAA receptor gating depends on extracellular pH.

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    Pytel, Maria; Mercik, Katarzyna; Mozrzymas, Jerzy W

    2005-11-28

    Recent studies have indicated that changes in extracellular pH and in membrane voltage affect the gamma-amino-n-butyric acid type A receptor gating mainly by altering desensitization and binding. To test whether the effects of membrane potential and pH are additive, their combined actions were investigated. By analyzing the current responses to rapid gamma-amino-n-butyric acid applications, we found that the current to voltage relationship was close to linear at acid pH but the increasing pH induced an inward rectification. Desensitization was enhanced at depolarizing potentials, but this strongly depended on pH, being weak at acidic and strong at basic pH values. A similar trend was observed for the onset rate of responses to saturating gamma-amino-n-butyric acid concentration. These data provide evidence that the voltage sensitivity of GABAA receptors depends on extracellular pH.

  8. The voltage dependence of GABAA receptor gating depends on extracellular pH

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    Pytel, Maria; Mercik, Katarzyna; Mozrzymas, Jerzy W.

    2007-01-01

    Recent studies have indicated that changes in extracellular pH and in membrane voltage affect the γ-amino-n-butyric acid type A receptor gating mainly by altering desensitization and binding. To test whether the effects of membrane potential and pH are additive, their combined actions were investigated. By analyzing the current responses to rapid γ-amino-n-butyric acid applications, we found that the current to voltage relationship was close to linear at acid pH but the increasing pH induced an inward rectification. Desensitization was enhanced at depolarizing potentials, but this strongly depended on pH, being weak at acidic and strong at basic pH values. A similar trend was observed for the onset rate of responses to saturating γ-amino-n-butyric acid concentration. These data provide evidence that the voltage sensitivity of GABAA receptors depends on extracellular pH. PMID:16272885

  9. Zn2+ regulates Kv2.1 voltage-dependent gating and localization following ischemia

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    Aras, Mandar A.; Saadi, Robert A.; Aizenman, Elias

    2009-01-01

    The delayed-rectifier K+ channel Kv2.1 exists in highly phosphorylated somatodendritic clusters. Ischemia induces rapid Kv2.1 dephosphorylation and a dispersal of these clusters, accompanied by a hyperpolarizing shift in their voltage-dependent activation kinetics. Transient modulation of Kv2.1 activity and localization following ischemia is dependent on a rise in intracellular Ca2+and the protein phosphatase calcineurin. Here, we show that neuronal free Zn2+also plays a critical role in the ...

  10. Voltage-dependent gating of hyperpolarization-activated, cyclic nucleotide-gated pacemaker channels: molecular coupling between the S4-S5 and C-linkers.

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    Decher, Niels; Chen, Jun; Sanguinetti, Michael C

    2004-04-02

    Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels have a transmembrane topology that is highly similar to voltage-gated K(+) channels, yet HCN channels open in response to membrane hyperpolarization instead of depolarization. The structural basis for the "inverted" voltage dependence of HCN gating and how voltage sensing by the S1-S4 domains is coupled to the opening of the intracellular gate formed by the S6 domain are unknown. Coupling could arise from interaction between specific residues or entire transmembrane domains. We previously reported that the mutation of specific residues in the S4-S5 linker of HCN2 (i.e. Tyr-331 and Arg-339) prevented normal channel closure presumably by disruption of a crucial interaction with the activation gate. Here we hypothesized that the C-linker, a carboxyl terminus segment that connects S6 to the cyclic nucleotide binding domain, interacts with specific residues of the S4-S5 linker to mediate coupling. The recently solved structure of the C-linker of HCN2 indicates that an alpha-helix (the A'-helix) is located near the end of each S6 domain, the presumed location of the activation gate. Ala-scanning mutagenesis of the end of S6 and the A'-helix identified five residues that were important for normal gating as mutations disrupted channel closure. However, partial deletion of the C-linker indicated that the presence of only two of these residues was required for normal coupling. Further mutation analyses suggested that a specific electrostatic interaction between Arg-339 of the S4-S5 linker and Asp-443 of the C-linker stabilizes the closed state and thus participates in the coupling of voltage sensing and activation gating in HCN channels.

  11. Probing the gate--voltage-dependent surface potential of individual InAs nanowires using random telegraph signals.

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    Salfi, Joe; Paradiso, Nicola; Roddaro, Stefano; Heun, Stefan; Nair, Selvakumar V; Savelyev, Igor G; Blumin, Marina; Beltram, Fabio; Ruda, Harry E

    2011-03-22

    We report a novel method for probing the gate-voltage dependence of the surface potential of individual semiconductor nanowires. The statistics of electronic occupation of a single defect on the surface of the nanowire, determined from a random telegraph signal, is used as a measure for the local potential. The method is demonstrated for the case of one or two switching defects in indium arsenide (InAs) nanowire field effect transistors at temperatures T=25-77 K. Comparison with a self-consistent model shows that surface potential variation is retarded in the conducting regime due to screening by surface states with density Dss≈10(12) cm(-2) eV(-1). Temperature-dependent dynamics of electron capture and emission producing the random telegraph signals are also analyzed, and multiphonon emission is identified as the process responsible for capture and emission of electrons from the surface traps. Two defects studied in detail had capture activation energies of EB≈50 meV and EB≈110 meV and cross sections of σ∞≈3×10(-19) cm2 and σ∞≈2×10(-17) cm2, respectively. A lattice relaxation energy of Sℏω=187±15 meV was found for the first defect.

  12. hERG S4-S5 linker acts as a voltage-dependent ligand that binds to the activation gate and locks it in a closed state.

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    Malak, Olfat A; Es-Salah-Lamoureux, Zeineb; Loussouarn, Gildas

    2017-12-01

    Delayed-rectifier potassium channels (hERG and KCNQ1) play a major role in cardiac repolarization. These channels are formed by a tetrameric pore (S5-S6) surrounded by four voltage sensor domains (S1-S4). Coupling between voltage sensor domains and the pore activation gate is critical for channel voltage-dependence. However, molecular mechanisms remain elusive. Herein, we demonstrate that covalently binding, through a disulfide bridge, a peptide mimicking the S4-S5 linker (S4-S5L) to the channel S6 C-terminus (S6T) completely inhibits hERG. This shows that channel S4-S5L is sufficient to stabilize the pore activation gate in its closed state. Conversely, covalently binding a peptide mimicking S6T to the channel S4-S5L prevents its inhibiting effect and renders the channel almost completely voltage-independent. This shows that the channel S4-S5L is necessary to stabilize the activation gate in its closed state. Altogether, our results provide chemical evidence that S4-S5L acts as a voltage-controlled ligand that binds S6T to lock the channel in a closed state, elucidating the coupling between voltage sensors and the gate in delayed rectifier potassium channels and potentially other voltage-gated channels.

  13. Aspartic Acid Residue D3 Critically Determines Cx50 Gap Junction Channel Transjunctional Voltage-Dependent Gating and Unitary Conductance

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    Xin, Li; Nakagawa, So; Tsukihara, Tomitake; Bai, Donglin

    2012-01-01

    Previous studies have suggested that the aspartic acid residue (D) at the third position is critical in determining the voltage polarity of fast Vj-gating of Cx50 channels. To test whether another negatively charged residue (a glutamic acid residue, E) could fulfill the role of the D3 residue, we generated the mutant Cx50D3E. Vj-dependent gating properties of this mutant channel were characterized by double-patch-clamp recordings in N2A cells. Macroscopically, the D3E substitution reduced the residual conductance (Gmin) to near zero and outwardly shifted the half-inactivation voltage (V0), which is a result of both a reduced aggregate gating charge (z) and a reduced free-energy difference between the open and closed states. Single Cx50D3E gap junction channels showed reduced unitary conductance (γj) of the main open state, reduced open dwell time at ±40 mV, and absence of a long-lived substate. In contrast, a G8E substitution tested to compare the effects of the E residue at the third and eighth positions did not modify the Vj-dependent gating profile or γj. In summary, this study is the first that we know of to suggest that the D3 residue plays an essential role, in addition to serving as a negative-charge provider, as a critical determinant of the Vj-dependent gating sensitivity, open-closed stability, and unitary conductance of Cx50 gap junction channels. PMID:22404924

  14. Temperature- and voltage-dependent trap generation model in high-k metal gate MOS device with percolation simulation

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    Xu, Hao; Yang, Hong; Wang, Yan-Rong; Wang, Wen-Wu; Luo, Wei-Chun; Qi, Lu-Wei; Li, Jun-Feng; Zhao, Chao; Chen, Da-Peng; Ye, Tian-Chun

    2016-08-01

    High-k metal gate stacks are being used to suppress the gate leakage due to tunneling for sub-45 nm technology nodes. The reliability of thin dielectric films becomes a limitation to device manufacturing, especially to the breakdown characteristic. In this work, a breakdown simulator based on a percolation model and the kinetic Monte Carlo method is set up, and the intrinsic relation between time to breakdown and trap generation rate R is studied by TDDB simulation. It is found that all degradation factors, such as trap generation rate time exponent m, Weibull slope β and percolation factor s, each could be expressed as a function of trap density time exponent α. Based on the percolation relation and power law lifetime projection, a temperature related trap generation model is proposed. The validity of this model is confirmed by comparing with experiment results. For other device and material conditions, the percolation relation provides a new way to study the relationship between trap generation and lifetime projection. Project supported by the National High Technology Research and Development Program of China (Grant No. SS2015AA010601), the National Natural Science Foundation of China (Grant Nos. 61176091 and 61306129), and the Opening Project of Key Laboratory of Microelectronics Devices & Integrated Technology, Institute of MicroElectronics of Chinese Academy of Sciences.

  15. The episodic ataxia type 1 mutation I262T alters voltage-dependent gating and disrupts protein biosynthesis of human Kv1.1 potassium channels.

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    Chen, Szu-Han; Fu, Ssu-Ju; Huang, Jing-Jia; Tang, Chih-Yung

    2016-01-18

    Voltage-gated potassium (Kv) channels are essential for setting neuronal membrane excitability. Mutations in human Kv1.1 channels are linked to episodic ataxia type 1 (EA1). The EA1-associated mutation I262T was identified from a patient with atypical phenotypes. Although a previous report has characterized its suppression effect, several key questions regarding the impact of the I262T mutation on Kv1.1 as well as other members of the Kv1 subfamily remain unanswered. Herein we show that the dominant-negative effect of I262T on Kv1.1 current expression is not reversed by co-expression with Kvβ1.1 or Kvβ2 subunits. Biochemical examinations indicate that I262T displays enhanced protein degradation and impedes membrane trafficking of Kv1.1 wild-type subunits. I262T appears to be the first EA1 mutation directly associated with impaired protein stability. Further functional analyses demonstrate that I262T changes the voltage-dependent activation and Kvβ1.1-mediated inactivation, uncouples inactivation from activation gating, and decelerates the kinetics of cumulative inactivation of Kv1.1 channels. I262T also exerts similar dominant effects on the gating of Kv1.2 and Kv1.4 channels. Together our data suggest that I262T confers altered channel gating and reduced functional expression of Kv1 channels, which may account for some of the phenotypes of the EA1 patient.

  16. The agonist-specific voltage dependence of M2 muscarinic receptors modulates the deactivation of the acetylcholine-gated K(+) current (I KACh).

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    Moreno-Galindo, Eloy G; Alamilla, Javier; Sanchez-Chapula, José A; Tristani-Firouzi, Martin; Navarro-Polanco, Ricardo A

    2016-07-01

    Recently, it has been shown that G protein-coupled receptors (GPCRs) display intrinsic voltage sensitivity. We reported that the voltage sensitivity of M2 muscarinic receptor (M2R) is also ligand specific. Here, we provide additional evidence to understand the mechanism underlying the ligand-specific voltage sensitivity of the M2R. Using ACh, pilocarpine (Pilo), and bethanechol (Beth), we evaluated the agonist-specific effects of voltage by measuring the ACh-activated K(+) current (I KACh) in feline and rabbit atrial myocytes and in HEK-293 cells expressing M2R-Kir3.1/Kir3.4. The activation of I KACh by the muscarinic agonist Beth was voltage insensitive, suggesting that the voltage-induced conformational changes in M2R do not modify its affinity for this agonist. Moreover, deactivation of the Beth-evoked I KACh was voltage insensitive. By contrast, deactivation of the ACh-induced I KACh was significantly slower at -100 mV than at +50 mV, while an opposite effect was observed when I KACh was activated by Pilo. These findings are consistent with the voltage affinity pattern observed for these three agonists. Our findings suggest that independent of how voltage disturbs the receptor binding site, the voltage dependence of the signaling pathway is ultimately determined by the agonist. These observations emphasize the pharmacological potential to regulate the M2R-parasympathetic associated cardiac function and also other cellular signaling pathways by exploiting the voltage-dependent properties of GPCRs.

  17. Conductance hysteresis in the voltage-dependent anion channel.

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    Rappaport, Shay M; Teijido, Oscar; Hoogerheide, David P; Rostovtseva, Tatiana K; Berezhkovskii, Alexander M; Bezrukov, Sergey M

    2015-09-01

    Hysteresis in the conductance of voltage-sensitive ion channels is observed when the transmembrane voltage is periodically varied with time. Although this phenomenon has been used in studies of gating of the voltage-dependent anion channel, VDAC, from the outer mitochondrial membrane for nearly four decades, full hysteresis curves have never been reported, because the focus was solely on the channel opening branches of the hysteresis loops. We studied the hysteretic response of a multichannel VDAC system to a triangular voltage ramp the frequency of which was varied over three orders of magnitude, from 0.5 mHz to 0.2 Hz. We found that in this wide frequency range the area encircled by the hysteresis curves changes by less than a factor of three, suggesting broad distribution of the characteristic times and strongly non-equilibrium behavior. At the same time, quasi-equilibrium two-state behavior is observed for hysteresis branches corresponding to VDAC opening. This enables calculation of the usual equilibrium gating parameters, gating charge and voltage of equipartitioning, which were found to be almost insensitive to the ramp frequency. To rationalize this peculiarity, we hypothesize that during voltage-induced closure and opening the system explores different regions of the complex free energy landscape, and, in the opening branch, follows quasi-equilibrium paths.

  18. STIR: Novel Electronic States by Gating Strongly Correlated Materials

    Science.gov (United States)

    2016-03-01

    understood, has long been the foundation for electronic devices. What if we could apply these techniques to a much broader range of materials ? This short...grant aimed at demonstrating such large potential modulations in correlated electron materials using a technique known as electrolyte gating. This...of Papers published in non peer-reviewed journals: Final Report: STIR: Novel Electronic States by Gating Strongly Correlated Materials Report Title

  19. Nonlinear properties of gated graphene in a strong electromagnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Avetisyan, A. A., E-mail: artakav@ysu.am; Djotyan, A. P., E-mail: adjotyan@ysu.am [Yerevan State University, Department of Physics (Armenia); Moulopoulos, K., E-mail: cos@ucy.ac.cy [University of Cyprus, Department of Physics (Cyprus)

    2017-03-15

    We develop a microscopic theory of a strong electromagnetic field interaction with gated bilayer graphene. Quantum kinetic equations for density matrix are obtained using a tight binding approach within second quantized Hamiltonian in an intense laser field. We show that adiabatically changing the gate potentials with time may produce (at resonant photon energy) a full inversion of the electron population with high density between valence and conduction bands. In the linear regime, excitonic absorption of an electromagnetic radiation in a graphene monolayer with opened energy gap is also studied.

  20. Voltage Dependence of Supercapacitor Capacitance

    Directory of Open Access Journals (Sweden)

    Szewczyk Arkadiusz

    2016-09-01

    Full Text Available Electronic Double-Layer Capacitors (EDLC, called Supercapacitors (SC, are electronic devices that are capable to store a relatively high amount of energy in a small volume comparing to other types of capacitors. They are composed of an activated carbon layer and electrolyte solution. The charge is stored on electrodes, forming the Helmholtz layer, and in electrolyte. The capacitance of supercapacitor is voltage- dependent. We propose an experimental method, based on monitoring of charging and discharging a supercapacitor, which enables to evaluate the charge in an SC structure as well as the Capacitance-Voltage (C-V dependence. The measurement setup, method and experimental results of charging/discharging commercially available supercapacitors in various voltage and current conditions are presented. The total charge stored in an SC structure is proportional to the square of voltage at SC electrodes while the charge on electrodes increases linearly with the voltage on SC electrodes. The Helmholtz capacitance increases linearly with the voltage bias while a sublinear increase of total capacitance was found. The voltage on SC increases after the discharge of electrodes due to diffusion of charges from the electrolyte to the electrodes. We have found that the recovery voltage value is linearly proportional to the initial bias voltage value.

  1. Voltage Dependence of Conformational Dynamics and Subconducting States of VDAC-1.

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    Briones, Rodolfo; Weichbrodt, Conrad; Paltrinieri, Licia; Mey, Ingo; Villinger, Saskia; Giller, Karin; Lange, Adam; Zweckstetter, Markus; Griesinger, Christian; Becker, Stefan; Steinem, Claudia; de Groot, Bert L

    2016-09-20

    The voltage-dependent anion channel 1 (VDAC-1) is an important protein of the outer mitochondrial membrane that transports energy metabolites and is involved in apoptosis. The available structures of VDAC proteins show a wide β-stranded barrel pore, with its N-terminal α-helix (N-α) bound to its interior. Electrophysiology experiments revealed that voltage, its polarity, and membrane composition modulate VDAC currents. Experiments with VDAC-1 mutants identified amino acids that regulate the gating process. However, the mechanisms for how these factors regulate VDAC-1, and which changes they trigger in the channel, are still unknown. In this study, molecular dynamics simulations and single-channel experiments of VDAC-1 show agreement for the current-voltage relationships of an "open" channel and they also show several subconducting transient states that are more cation selective in the simulations. We observed voltage-dependent asymmetric distortions of the VDAC-1 barrel and the displacement of particular charged amino acids. We constructed conformational models of the protein voltage response and the pore changes that consistently explain the protein conformations observed at opposite voltage polarities, either in phosphatidylethanolamine or phosphatidylcholine membranes. The submicrosecond VDAC-1 voltage response shows intrinsic structural changes that explain the role of key gating amino acids and support some of the current gating hypotheses. These voltage-dependent protein changes include asymmetric barrel distortion, its interaction with the membrane, and significant displacement of N-α amino acids.

  2. KCNQ1 Channels Voltage Dependence through a Voltage-dependent Binding of the S4-S5 Linker to the Pore Domain*

    OpenAIRE

    2010-01-01

    Voltage-dependent potassium (Kv) channels are tetramers of six transmembrane domain (S1–S6) proteins. Crystallographic data demonstrate that the tetrameric pore (S5–S6) is surrounded by four voltage sensor domains (S1–S4). One key question remains: how do voltage sensors (S4) regulate pore gating? Previous mutagenesis data obtained on the Kv channel KCNQ1 highlighted the critical role of specific residues in both the S4-S5 linker (S4S5L) and S6 C terminus (S6T). From these data, we hypothesiz...

  3. The effects of S4 segments on the voltage-dependence of inactivation for Cav3.1 calcium channels

    Institute of Scientific and Technical Information of China (English)

    LI JunYing

    2007-01-01

    T-type calcium channels exhibit fast voltage-dependent inactivation,for which the underlying structure-function relationship still remains unclear.To investigate the roles of S4 segments in voltage-dependent inactivation of T-type calcium channels,we created S4 replacement chimeras between Cav3.1 calcium channels(fast voltage-dependent inactivation)and Cav1.2 calcium channels(little oltage-dependent inactivation)by replacing S4s in Cav3.1 with the corresponding regions in Cav1.2.Wild type and chimeric channels were expressed in Xenopus oocytes and channel currents were recorded with two-electrode voltage-clamp.We showed that replacing S4 region in domain I shifted voltage-dependence for inactivation of Cav3.1 to the left,and the V0.5 inact and kinact value were significantly changed.However replacing S4s in domains Ⅱ-Ⅳ had no effects on the voltage-dependent inactivation properties.These results suggest that the roles of S4 segments in domains Ⅰ-Ⅳ are different,and S4 in domain I is likely to be involved in voltage-dependent Inactivation process.Its movement during membrane depolarization may trigger a conformational change in the inactivation gate.

  4. Calmodulin and calcium differentially regulate the neuronal Nav1.1 voltage-dependent sodium channel

    Energy Technology Data Exchange (ETDEWEB)

    Gaudioso, Christelle; Carlier, Edmond; Youssouf, Fahamoe [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France); Clare, Jeffrey J. [Eaton Pharma Consulting, Eaton Socon, Cambridgeshire PE19 8EF (United Kingdom); Debanne, Dominique [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France); Alcaraz, Gisele, E-mail: gisele.alcaraz@univmed.fr [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France)

    2011-07-29

    Highlights: {yields} Both Ca{sup ++}-Calmodulin (CaM) and Ca{sup ++}-free CaM bind to the C-terminal region of Nav1.1. {yields} Ca{sup ++} and CaM have both opposite and convergent effects on I{sub Nav1.1}. {yields} Ca{sup ++}-CaM modulates I{sub Nav1.1} amplitude. {yields} CaM hyperpolarizes the voltage-dependence of activation, and increases the inactivation rate. {yields} Ca{sup ++} alone antagonizes CaM for both effects, and depolarizes the voltage-dependence of inactivation. -- Abstract: Mutations in the neuronal Nav1.1 voltage-gated sodium channel are responsible for mild to severe epileptic syndromes. The ubiquitous calcium sensor calmodulin (CaM) bound to rat brain Nav1.1 and to the human Nav1.1 channel expressed by a stably transfected HEK-293 cell line. The C-terminal region of the channel, as a fusion protein or in the yeast two-hybrid system, interacted with CaM via a consensus C-terminal motif, the IQ domain. Patch clamp experiments on HEK1.1 cells showed that CaM overexpression increased peak current in a calcium-dependent way. CaM had no effect on the voltage-dependence of fast inactivation, and accelerated the inactivation kinetics. Elevating Ca{sup ++} depolarized the voltage-dependence of fast inactivation and slowed down the fast inactivation kinetics, and for high concentrations this effect competed with the acceleration induced by CaM alone. Similarly, the depolarizing action of calcium antagonized the hyperpolarizing shift of the voltage-dependence of activation due to CaM overexpression. Fluorescence spectroscopy measurements suggested that Ca{sup ++} could bind the Nav1.1 C-terminal region with micromolar affinity.

  5. Voltage dependence of the Na-K pump.

    Science.gov (United States)

    De Weer, P; Gadsby, D C; Rakowski, R F

    1988-01-01

    Present evidence demonstrates that the Na-K pump rate is voltage dependent, whereas early work was largely inconclusive. The I-V relationship has a positive slope over a wide voltage range, and the existence of a negative slope region is now doubtful. Monotonic voltage dependence is consistent with the reaction cycle containing a single voltage-dependent step. Recent measurements suggest that this voltage-dependent step occurs during Na translocation and may be deocclusion of Na+. In addition, two results suggest that K translocation is voltage insensitive: (a) large positive potentials appear to have no influence on Rb-Rb exchange or associated conformational transitions; and (b) transient currents associated with Na translocation appear to involve movement of a single charge, which is sufficient for a 3Na-2K cycle. The simplest interpretation is that the pump's cation binding sites supply two negative charges. Pre-steady-state measurements demonstrate that Na translocation precedes the pump cycle's rate-limiting step, presumably K translocation. But, because K translocation seems voltage insensitive, the voltage dependence of the steady-state pump rate probably reflects that of the concentration of the intermediate entering this slow step. Further pump current and flux data (both transient and steady-state), carefully determined over a range of conditions, should increase our understanding of the voltage-dependent step(s) in the Na-K pump cycle.

  6. Voltage-dependent calcium channels from brain incorporated into planar lipid bilayers

    Science.gov (United States)

    Nelson, Mark T.; French, Robert J.; Krueger, Bruce K.

    1984-03-01

    Many important physiological processes, including neurotransmitter release and muscle contraction1-3, are regulated by the concentration of Ca2+ ions in the cell. Levels of cytoplasmic Ca2+ can be elevated by the entry of Ca2+ ions through voltage-dependent channels which are selective for Ca2+, Ba2+ and Sr2+ ions4-14. We have measured currents through single, voltage-dependent calcium channels from rat brain that have been incorporated into planar lipid bilayers. Channel gating was voltage-dependent: membrane depolarization increased the channel open times and decreased the closed times. The channels were selective for divalent cations over monovalent ions. The well-known calcium channel blockers, lanthanum and cadmium, produced a concentration-dependent reduction of the apparent single-channel conductance. Contrary to expectations14, the nature of the divalent cation carrying current through the channel affected not only the single-channel conductance, but also the channel open times, with mean open times being shortest for barium.

  7. Conducting and voltage-dependent behaviors of potassium ion channels reconstituted from diaphragm sarcoplasmic reticulum: comparison with the cardiac isoform.

    Science.gov (United States)

    Picher, M; Decrouy, A; Rousseau, E

    1996-02-21

    Sarcoplasmic reticulum (SR) K+ channels from canine diaphragm were studied upon fusion of longitudinal and junctional membrane vesicles into planar lipid bilayers (PLB). The large-conductance cation selective channel (gamma(max) = 250 pS; Km = 33 mM) displays long-lasting open events which are much more frequent at positive than at negative voltages. A major subconducting state about 45% of the fully-open state current amplitude was occasionally observed at all voltages. The voltage-dependence of the open probability displays a sigmoid relationship that was fitted by the Boltzmann equation and expressed in terms of thermodynamic parameters, namely the free energy (delta Gi) and the effective gating charge (Zs): delta Gi = 0.27 kcal/mol and Zs = -1.19 in 250 mM potassium gluconate (K-gluconate). Kinetic analyses also confirmed the voltage-dependent gating behavior of this channel, and indicate the implication of at least two open and three closed states. The diaphragm SR K+ channel shares several biophysical properties with the cardiac isoform: g = 180 pS, delta Gi = 0.75 kcal/mol, Zs = -1.45 in 150 mM K-gluconate, and a similar sigmoid P(o)/voltage relationship. Little is known about the regulation of the diaphragm and cardiac SR K+ channels. The conductance and gating of these channels were not influenced by physiological concentrations of Ca2+ (0.1 microM-1 mM) or Mg2+ (0.25-1 mM), as well as by cGMP (25-100 microM), lemakalim (1-100 microM), glyburide (up to 10 microM) or charybdotoxin (45-200 nM), added either to the cis or to the trans chamber. The apparent lack of biochemical or pharmacological modulation of these channels implies that they are not related to any of the well characterized surface membrane K+ channels. On the other hand, their voltage sensitivity strongly suggests that their activity could be modulated by putative changes in SR membrane potential that might occur during calcium fluxes.

  8. Voltage-dependent regulation of CaV2.2 channels by Gq-coupled receptor is facilitated by membrane-localized β subunit.

    Science.gov (United States)

    Keum, Dongil; Baek, Christina; Kim, Dong-Il; Kweon, Hae-Jin; Suh, Byung-Chang

    2014-10-01

    G protein-coupled receptors (GPCRs) signal through molecular messengers, such as Gβγ, Ca(2+), and phosphatidylinositol 4,5-bisphosphate (PIP2), to modulate N-type voltage-gated Ca(2+) (CaV2.2) channels, playing a crucial role in regulating synaptic transmission. However, the cellular pathways through which GqPCRs inhibit CaV2.2 channel current are not completely understood. Here, we report that the location of CaV β subunits is key to determining the voltage dependence of CaV2.2 channel modulation by GqPCRs. Application of the muscarinic agonist oxotremorine-M to tsA-201 cells expressing M1 receptors, together with CaV N-type α1B, α2δ1, and membrane-localized β2a subunits, shifted the current-voltage relationship for CaV2.2 activation 5 mV to the right and slowed current activation. Muscarinic suppression of CaV2.2 activity was relieved by strong depolarizing prepulses. Moreover, when the C terminus of β-adrenergic receptor kinase (which binds Gβγ) was coexpressed with N-type channels, inhibition of CaV2.2 current after M1 receptor activation was markedly reduced and delayed, whereas the delay between PIP2 hydrolysis and inhibition of CaV2.2 current was decreased. When the Gβγ-insensitive CaV2.2 α1C-1B chimera was expressed, voltage-dependent inhibition of calcium current was virtually abolished, suggesting that M1 receptors act through Gβγ to inhibit CaV2.2 channels bearing membrane-localized CaV β2a subunits. Expression of cytosolic β subunits such as β2b and β3, as well as the palmitoylation-negative mutant β2a(C3,4S), reduced the voltage dependence of M1 muscarinic inhibition of CaV2.2 channels, whereas it increased inhibition mediated by PIP2 depletion. Together, our results indicate that, with membrane-localized CaV β subunits, CaV2.2 channels are subject to Gβγ-mediated voltage-dependent inhibition, whereas cytosol-localized β subunits confer more effective PIP2-mediated voltage-independent regulation. Thus, the voltage dependence of

  9. The voltage dependence of Ih in human myelinated axons

    Science.gov (United States)

    Howells, James; Trevillion, Louise; Bostock, Hugh; Burke, David

    2012-01-01

    HCN channels are responsible for Ih, a voltage-gated inwardly rectifying current activated by hyperpolarization. This current appears to be more active in human sensory axons than motor and may play a role in the determination of threshold. Differences in Ih are likely to be responsible for the high variability in accommodation to hyperpolarization seen in different subjects. The aim of this study was to characterise this current in human axons, both motor and sensory. Recordings of multiple axonal excitability properties were performed in 10 subjects, with a focus on the changes in threshold evoked by longer and stronger hyperpolarizing currents than normally studied. The findings confirm that accommodation to hyperpolarization is greater in sensory than motor axons in all subjects, but the variability between subjects was greater than the modality difference. An existing model of motor axons was modified to take into account the behaviour seen with longer and stronger hyperpolarization, and a mathematical model of human sensory axons was developed based on the data collected. The differences in behaviour of sensory and motor axons and the differences between different subjects are best explained by modulation of the voltage dependence, along with a modest increase of expression of the underlying conductance of Ih. Accommodation to hyperpolarization for the mean sensory data is fitted well with a value of −94.2 mV for the mid-point of activation (V0.5) of Ih as compared to −107.3 mV for the mean motor data. The variation in response to hyperpolarization between subjects is accounted for by varying this parameter for each modality (sensory: −89.2 to −104.2 mV; motor −87.3 to −127.3 mV). These voltage differences are within the range that has been described for physiological modulation of Ih function. The presence of slowly activated Ih isoforms on both motor and sensory axons was suggested by modelling a large internodal leak current and a masking of

  10. Voltage-dependent metabolic regulation of Kv2.1 channels in pancreatic beta-cells.

    Science.gov (United States)

    Yoshida, Masashi; Nakata, Masanori; Yamato, Shiho; Dezaki, Katsuya; Sugawara, Hitoshi; Ishikawa, San-e; Kawakami, Masanobu; Yada, Toshihiko; Kakei, Masafumi

    2010-05-28

    Voltage-gated potassium channels (Kv channels) play a crucial role in formation of action potentials in response to glucose stimulation in pancreatic beta-ells. We previously reported that the Kv channel is regulated by glucose metabolism, particularly by MgATP. We examined whether the regulation of Kv channels is voltage-dependent and mechanistically related with phosphorylation of the channels. In rat pancreatic beta-cells, suppression of glucose metabolism with low glucose concentrations of 2.8mM or less or by metabolic inhibitors decreased the Kv2.1-channel activity at positive membrane potentials, while increased it at potentials negative to -10 mV, suggesting that modulation of Kv channels by glucose metabolism is voltage-dependent. Similarly, in HEK293 cells expressing the recombinant Kv2.1 channels, 0mM but not 10mM MgATP modulated the channel activity in a manner similar to that in beta-cells. Both steady-state activation and inactivation kinetics of the channel were shifted toward the negative potential in association with the voltage-dependent modulation of the channels by cytosolic dialysis of alkaline phosphatase in beta-cells. The modulation of Kv-channel current-voltage relations were also observed during and after glucose-stimulated electrical excitation. These results suggest that the cellular metabolism including MgATP production and/or channel phosphorylation/dephosphorylation underlie the physiological modulation of Kv2.1 channels during glucose-induced insulin secretion.

  11. Hypotonicity activates a voltage-dependent membrane conductance in N2a neuroblastoma cells.

    Science.gov (United States)

    Taruno, Akiyuki; Marunaka, Yoshinori

    2017-03-04

    To maintain cellular and bodily homeostasis, cells respond to extracellular stimuli including osmotic stress by activating various ion channels, which have been implicated in many physiological and pathophysiological conditions. However, cellular osmosensory mechanisms remain elusive. Here, we report a novel voltage-dependent current in N2a cells activated by exposure to hypotonic stress. After a hypotonic challenge, N2a cells sequentially develop two distinct currents. The volume-regulated anion channel (VRAC) current emerges first and, after a delay, activation of a previously uncharacterized strongly outwardly rectifying current follows. The latter, delayed current (Id) is insensitive to NPPB, a nonspecific blocker of Cl(-) channels, and intracellular Mg(2+), which inhibits VRAC and swelling-activated TRPM3 and TRPM7 channels. Replacement of extracellular Na(+) with NMDG(+) reduces inward tail currents, suggesting that Id is mediated by cations. Finally, Id shows voltage-dependent activation with slow activation kinetics and half-maximal activation at +76 mV. These pharmacological and biophysical characteristics of Id are distinct from those of known osmotic cell swelling-activated ion channels. In conclusion, our data identify and characterize a novel osmotically-activated, voltage-dependent ion channel in N2a cells.

  12. Endocytic regulation of voltage-dependent potassium channels in the heart.

    Science.gov (United States)

    Ishii, Kuniaki; Norota, Ikuo; Obara, Yutaro

    2012-01-01

    Understanding the regulation of cardiac ion channels is critical for the prevention of arrhythmia caused by abnormal excitability. Ion channels can be regulated by a change in function (qualitative) and a change in number (quantitative). Functional changes have been extensively investigated for many ion channels including cardiac voltage-dependent potassium channels. By contrast, the regulation of ion channel numbers has not been widely examined, particularly with respect to acute modulation of ion channels. This article briefly summarizes stimulus-induced endocytic regulation of major voltage-dependent potassium channels in the heart. The stimuli known to cause their endocytosis include receptor activation, drugs, and low extracellular [K(+)], following which the potassium channels undergo either clathrin-mediated or caveolin-mediated endocytosis. Receptor-mediated endocytic regulation has been demonstrated for Kv1.2, Kv1.5, KCNQ1 (Kv7.1), and Kv4.3, while drug-induced endocytosis has been demonstrated for Kv1.5 and hERG. Low [K(+)](o)-induced endocytosis might be unique for hERG channels, whose electrophysiological characteristics are known to be under strong influence of [K(+)](o). Although the precise mechanisms have not been elucidated, it is obvious that major cardiac voltage-dependent potassium channels are modulated by endocytosis, which leads to changes in cardiac excitability.

  13. A vesicle-trafficking protein commandeers Kv channel voltage sensors for voltage-dependent secretion.

    Science.gov (United States)

    Grefen, Christopher; Karnik, Rucha; Larson, Emily; Lefoulon, Cécile; Wang, Yizhou; Waghmare, Sakharam; Zhang, Ben; Hills, Adrian; Blatt, Michael R

    2015-01-01

    Growth in plants depends on ion transport for osmotic solute uptake and secretory membrane trafficking to deliver material for wall remodelling and cell expansion. The coordination of these processes lies at the heart of the question, unresolved for more than a century, of how plants regulate cell volume and turgor. Here we report that the SNARE protein SYP121 (SYR1/PEN1), which mediates vesicle fusion at the Arabidopsis plasma membrane, binds the voltage sensor domains (VSDs) of K(+) channels to confer a voltage dependence on secretory traffic in parallel with K(+) uptake. VSD binding enhances secretion in vivo subject to voltage, and mutations affecting VSD conformation alter binding and secretion in parallel with channel gating, net K(+) concentration, osmotic content and growth. These results demonstrate a new and unexpected mechanism for secretory control, in which a subset of plant SNAREs commandeer K(+) channel VSDs to coordinate membrane trafficking with K(+) uptake for growth.

  14. Reversal of HCN channel voltage dependence via bridging of the S4-S5 linker and Post-S6.

    Science.gov (United States)

    Prole, David L; Yellen, Gary

    2006-09-01

    Voltage-gated ion channels possess charged domains that move in response to changes in transmembrane voltage. How this movement is transduced into gating of the channel pore is largely unknown. Here we show directly that two functionally important regions of the spHCN1 pacemaker channel, the S4-S5 linker and the C-linker, come into close proximity during gating. Cross-linking these regions with high-affinity metal bridges or disulfide bridges dramatically alters channel gating in the absence of cAMP; after modification the polarity of voltage dependence is reversed. Instead of being closed at positive voltage and activating with hyperpolarization, modified channels are closed at negative voltage and activate with depolarization. Mechanistically, this reversal of voltage dependence occurs as a result of selectively eliminating channel deactivation, while retaining an existing inactivation process. Bridging also alters channel activation by cAMP, showing that interaction of these two regions can also affect the efficacy of physiological ligands.

  15. KCNQ1 channels voltage dependence through a voltage-dependent binding of the S4-S5 linker to the pore domain.

    Science.gov (United States)

    Choveau, Frank S; Rodriguez, Nicolas; Abderemane Ali, Fayal; Labro, Alain J; Rose, Thierry; Dahimène, Shehrazade; Boudin, Hélène; Le Hénaff, Carole; Escande, Denis; Snyders, Dirk J; Charpentier, Flavien; Mérot, Jean; Baró, Isabelle; Loussouarn, Gildas

    2011-01-07

    Voltage-dependent potassium (Kv) channels are tetramers of six transmembrane domain (S1-S6) proteins. Crystallographic data demonstrate that the tetrameric pore (S5-S6) is surrounded by four voltage sensor domains (S1-S4). One key question remains: how do voltage sensors (S4) regulate pore gating? Previous mutagenesis data obtained on the Kv channel KCNQ1 highlighted the critical role of specific residues in both the S4-S5 linker (S4S5(L)) and S6 C terminus (S6(T)). From these data, we hypothesized that S4S5(L) behaves like a ligand specifically interacting with S6(T) and stabilizing the closed state. To test this hypothesis, we designed plasmid-encoded peptides corresponding to portions of S4S5(L) and S6(T) of the voltage-gated potassium channel KCNQ1 and evaluated their effects on the channel activity in the presence and absence of the ancillary subunit KCNE1. We showed that S4S5(L) peptides inhibit KCNQ1, in a reversible and state-dependent manner. S4S5(L) peptides also inhibited a voltage-independent KCNQ1 mutant. This inhibition was competitively prevented by a peptide mimicking S6(T), consistent with S4S5(L) binding to S6(T). Val(254) in S4S5(L) is known to contact Leu(353) in S6(T) when the channel is closed, and mutations of these residues alter the coupling between the two regions. The same mutations introduced in peptides altered their effects, further confirming S4S5(L) binding to S6(T). Our results suggest a mechanistic model in which S4S5(L) acts as a voltage-dependent ligand bound to its receptor on S6 at rest. This interaction locks the channel in a closed state. Upon plasma membrane depolarization, S4 pulls S4S5(L) away from S6(T), allowing channel opening.

  16. Origin of the voltage dependence of G-protein regulation of P/Q-type Ca2+ channels.

    Science.gov (United States)

    Zhang, Yun; Chen, Yu-Hang; Bangaru, Saroja D; He, Linling; Abele, Kathryn; Tanabe, Shihori; Kozasa, Tohru; Yang, Jian

    2008-12-24

    G-protein (Gbetagamma)-mediated voltage-dependent inhibition of N- and P/Q-type Ca(2+) channels contributes to presynaptic inhibition and short-term synaptic plasticity. The voltage dependence derives from the dissociation of Gbetagamma from the inhibited channels, but the underlying molecular and biophysical mechanisms remain largely unclear. In this study we investigated the role in this process of Ca(2+) channel beta subunit (Ca(v)beta) and a rigid alpha-helical structure between the alpha-interacting domain (AID), the primary Ca(v)beta docking site on the channel alpha(1) subunit, and the pore-lining IS6 segment. Gbetagamma inhibition of P/Q-type channels was reconstituted in giant inside-out membrane patches from Xenopus oocytes. Large populations of channels devoid of Ca(v)beta were produced by washing out a mutant Ca(v)beta with a reduced affinity for the AID. These beta-less channels were still inhibited by Gbetagamma, but without any voltage dependence, indicating that Ca(v)beta is indispensable for voltage-dependent Gbetagamma inhibition. A truncated Ca(v)beta containing only the AID-binding guanylate kinase (GK) domain could fully confer voltage dependence to Gbetagamma inhibition. Gbetagamma did not alter inactivation properties, and channels recovered from Gbetagamma inhibition exhibited the same activation property as un-inhibited channels, indicating that Gbetagamma does not dislodge Ca(v)beta from the inhibited channel. Furthermore, voltage-dependent Gbetagamma inhibition was abolished when the rigid alpha-helix between the AID and IS6 was disrupted by insertion of multiple glycines, which also eliminated Ca(v)beta regulation of channel gating, revealing a pivotal role of this rigid alpha-helix in both processes. These results suggest that depolarization-triggered movement of IS6, coupled to the subsequent conformational change of the Gbetagamma-binding pocket through a rigid alpha-helix induced partly by the Ca(v)beta GK domain, causes the

  17. The Eag domain regulates the voltage-dependent inactivation of rat Eag1 K+ channels.

    Directory of Open Access Journals (Sweden)

    Ting-Feng Lin

    Full Text Available Eag (Kv10 and Erg (Kv11 belong to two distinct subfamilies of the ether-à-go-go K+ channel family (KCNH. While Erg channels are characterized by an inward-rectifying current-voltage relationship that results from a C-type inactivation, mammalian Eag channels display little or no voltage-dependent inactivation. Although the amino (N-terminal region such as the eag domain is not required for the C-type inactivation of Erg channels, an N-terminal deletion in mouse Eag1 has been shown to produce a voltage-dependent inactivation. To further discern the role of the eag domain in the inactivation of Eag1 channels, we generated N-terminal chimeras between rat Eag (rEag1 and human Erg (hERG1 channels that involved swapping the eag domain alone or the complete cytoplasmic N-terminal region. Functional analyses indicated that introduction of the homologous hERG1 eag domain led to both a fast phase and a slow phase of channel inactivation in the rEag1 chimeras. By contrast, the inactivation features were retained in the reverse hERG1 chimeras. Furthermore, an eag domain-lacking rEag1 deletion mutant also showed the fast phase of inactivation that was notably attenuated upon co-expression with the rEag1 eag domain fragment, but not with the hERG1 eag domain fragment. Additionally, we have identified a point mutation in the S4-S5 linker region of rEag1 that resulted in a similar inactivation phenotype. Biophysical analyses of these mutant constructs suggested that the inactivation gating of rEag1 was distinctly different from that of hERG1. Overall, our findings are consistent with the notion that the eag domain plays a critical role in regulating the inactivation gating of rEag1. We propose that the eag domain may destabilize or mask an inherent voltage-dependent inactivation of rEag1 K+ channels.

  18. Pharmacology of the human cell voltage-dependent cation channel. Part II: inactivation and blocking

    DEFF Research Database (Denmark)

    Bennekou, Poul; Barksmann, Trine L.; Kristensen, Berit I.

    2004-01-01

    Human red cells; Nonselective voltage-dependent cation channel; NSVDC channel; Thiol group reagents......Human red cells; Nonselective voltage-dependent cation channel; NSVDC channel; Thiol group reagents...

  19. SKF-96365 strongly inhibits voltage-gated sodium current in rat ventricular myocytes.

    Science.gov (United States)

    Chen, Kui-Hao; Liu, Hui; Yang, Lei; Jin, Man-Wen; Li, Gui-Rong

    2015-06-01

    SKF-96365 (1-(beta-[3-(4-methoxy-phenyl) propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride) is a general TRPC channel antagonist commonly used to characterize the potential functions of TRPC channels in cardiovascular system. Recent reports showed that SKF-96365 induced a reduction in cardiac conduction. The present study investigates whether the reduced cardiac conduction caused by SKF-96365 is related to the blockade of voltage-gated sodium current (I Na) in rat ventricular myocytes using the whole-cell patch voltage-clamp technique. It was found that SKF-96365 inhibited I Na in rat ventricular myocytes in a concentration-dependent manner. The compound (1 μM) negatively shifted the potential of I Na availability by 9.5 mV, increased the closed-state inactivation of I Na, and slowed the recovery of I Na from inactivation. The inhibition of cardiac I Na by SKF-96365 was use-dependent and frequency-dependent, and the IC₅₀ was decreased from 1.36 μM at 0.5 Hz to 1.03, 0.81, 0.61, 0.56 μM at 1, 2, 5, 10 Hz, respectively. However, the selective TRPC3 antagonist Pyr3 decreased cardiac I Na by 8.5% at 10 μM with a weak use and frequency dependence. These results demonstrate that the TRPC channel antagonist SKF-96365 strongly blocks cardiac I Na in use-dependent and frequency-dependent manners. Caution should be taken for interpreting the alteration of cardiac electrical activity when SKF-96365 is used in native cells as a TRPC antagonist.

  20. Manipulating the voltage dependence of tunneling spin torques

    KAUST Repository

    Manchon, Aurelien

    2012-10-01

    Voltage-driven spin transfer torques in magnetic tunnel junctions provide an outstanding tool to design advanced spin-based devices for memory and reprogrammable logic applications. The non-linear voltage dependence of the torque has a direct impact on current-driven magnetization dynamics and on devices performances. After a brief overview of the progress made to date in the theoretical description of the spin torque in tunnel junctions, I present different ways to alter and control the bias dependence of both components of the spin torque. Engineering the junction (barrier and electrodes) structural asymmetries or controlling the spin accumulation profile in the free layer offer promising tools to design effcient spin devices.

  1. Tetrahydroacridine inhibits voltage-dependent Na+ current in guinea-pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Wei WANG; Yi-ping WANG; Guo-yuan HU

    2004-01-01

    AIM: To study the effects of tetrahydroacridine (tacrine) on voltage-gated Na+ channels in cardiac tissues.METHODS: Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltagedependent Na+ current was recorded using whole cell voltage-clamp technique. RESULTS: (1) Tacrine reversibly inhibited Na+ current with an IC50 value of 120 μmol/L (95 % confidence range: 108-133 μmol/L). (2) The inhibitory effects of tacrine on Na+ current exhibited both a tonic nature and use-dependence. (3) Tacrine at 100 μmol/L caused a negative shift (about 10 mV) in the voltage-dependence of steady-state inactivation of Na+ current, and retarded its recovery from inactivation, but did not affect its activation curve. (4) Intracellular application of tacrine significantly inhibited Na+ current. CONCLUSION: In addition to blocking other voltage-gated ion channels,tacrine blocked Na+ channels in guinea-pig ventricular myocytes. Tactine acted as inactivation stabilizer of Na+channels in cardiac tissues.

  2. Multiple mechanisms underlying rectification in retinal cyclic nucleotide-gated (CNGA1) channels.

    Science.gov (United States)

    Arcangeletti, Manuel; Marchesi, Arin; Mazzolini, Monica; Torre, Vincent

    2013-11-01

    In cyclic nucleotide-gated (CNGA1) channels, in the presence of symmetrical ionic conditions, current-voltage (I-V) relationship depends, in a complex way, on the radius of permeating ion. It has been suggested that both the pore and S4 helix contribute to the observed rectification. In the present manuscript, using tail and gating current measurements from homotetrameric CNGA1 channels expressed in Xenopus oocytes, we clarify and quantify the role of the pore and of the S4 helix. We show that in symmetrical Rb(+) and Cs(+) single-channel current rectification dominates macroscopic currents while voltage-dependent gating becomes larger in symmetrical ethylammonium and dimethylammonium, where the open probability strongly depends on voltage. Isochronal tail currents analysis in dimethylammonium shows that at least two voltage-dependent transitions underlie the observed rectification. Only the first voltage-dependent transition is sensible to mutation of charge residues in the S4 helix. Moreover, analysis of tail and gating currents indicates that the number of elementary charges per channel moving across the membrane is less than 2, when they are about 12 in K(+) channels. These results indicate the existence of distinct mechanisms underlying rectification in CNG channels. A restricted motion of the S4 helix together with an inefficient coupling to the channel gate render CNGA1 channels poorly sensitive to voltage in the presence of physiological Na(+) and K(+).

  3. [Role of voltage-dependent ion channels in epileptogenesis].

    Science.gov (United States)

    Ricard-Mousnier, B; Couraud, F

    1993-10-01

    The aim of this review is to gather information in favour of the involvement of voltage-dependent ion channels in epileptogenesis. Although, up to now, no study has shown that epilepsy is accompanied by a modification in the activity to these channels, the recently acquired knowledge of their physiology allows to presume would favor their involvement in epileptogenesis. The results from electrophysiological studies are as follows: a persistent sodium current increases neuronal excitability whereas potassium currents have an inhibitory role. In particular, calcium-dependent potassium current are involved in the post-hyperpolarization phases which follows PDS. Calcium currents are also involved in the genesis of the "bursting pacemaker" activity displayed by the neurons presumed to be inducers of the epileptic activity. Biochemical data has shown that as a consequence of epileptic activity, sodium and calcium channels are down regulated. This down-regulation could be a way to reduces neuronal hyperexcitability. Pharmacological data demonstrate the drugs which activate calcium channels or which inhibit potassium channels have a convusilvant effect. On the contrary, agents which block calcium or sodium channels or which properties. Among the latter ones, some antiepileptic drugs can be found. In summary situations which lead to increase in calcium and sodium currents and/or to an inhibition in potassium currents are potentially epileptogenic.

  4. Voltage-gated Proton Channels

    Science.gov (United States)

    DeCoursey, Thomas E.

    2014-01-01

    Voltage-gated proton channels, HV1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely the mechanism by which voltage-dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage-sensing domain of most other voltage-gated ion channels. Unique, or at least eccentric, properties of proton channels include dimeric architecture with dual conduction pathways, perfect proton selectivity, a single-channel conductance ~103 smaller than most ion channels, voltage-dependent gating that is strongly modulated by the pH gradient, ΔpH, and potent inhibition by Zn2+ (in many species) but an absence of other potent inhibitors. The recent identification of HV1 in three unicellular marine plankton species has dramatically expanded the phylogenetic family tree. Interest in proton channels in their own right has increased as important physiological roles have been identified in many cells. Proton channels trigger the bioluminescent flash of dinoflagellates, facilitate calcification by coccolithophores, regulate pH-dependent processes in eggs and sperm during fertilization, secrete acid to control the pH of airway fluids, facilitate histamine secretion by basophils, and play a signaling role in facilitating B-cell receptor mediated responses in B lymphocytes. The most elaborate and best-established functions occur in phagocytes, where proton channels optimize the activity of NADPH oxidase, an important producer of reactive oxygen species. Proton efflux mediated by HV1 balances the charge translocated across the membrane by electrons through NADPH oxidase, minimizes changes in cytoplasmic and phagosomal pH, limits osmotic swelling of the phagosome, and provides substrate H+ for the production of H2O2 and HOCl, reactive oxygen species crucial to killing pathogens. PMID:23798303

  5. Phosphorylation of purified mitochondrial Voltage-Dependent Anion Channel by c-Jun N-terminal Kinase-3 modifies channel voltage-dependence

    Directory of Open Access Journals (Sweden)

    Rajeev Gupta

    2017-06-01

    Full Text Available Voltage-Dependent Anion Channel (VDAC phosphorylated by c-Jun N-terminal Kinase-3 (JNK3 was incorporated into the bilayer lipid membrane. Single-channel electrophysiological properties of the native and the phosphorylated VDAC were compared. The open probability versus voltage curve of the native VDAC displayed symmetry around the voltage axis, whereas that of the phosphorylated VDAC showed asymmetry. This result indicates that phosphorylation by JNK3 modifies voltage-dependence of VDAC.

  6. Regulation of KV channel voltage-dependent activation by transmembrane β subunits

    Directory of Open Access Journals (Sweden)

    Xiaohui eSun

    2012-04-01

    Full Text Available Voltage-activated K+ (KV channels are important for shaping action potentials and maintaining resting membrane potential in excitable cells. KV channels contain a central pore-gate domain (PGD surrounded by four voltage-sensing domains (VSD. The VSDs will change conformation in response to alterations of the membrane potential thereby inducing the opening of the PGD. Many KV channels are heteromeric protein complexes containing auxiliary β subunits. These β subunits modulate channel expression and activity to increase functional diversity and render tissue specific phenotypes. This review focuses on the KV β subunits that contain transmembrane (TM segments including the KCNE family and the β subunits of large conductance, Ca2+- and voltage-activated K+ (BK channels. These TM β subunits affect the voltage-dependent activation of KV α subunits. Experimental and computational studies have described the structural location of these β subunits in the channel complexes and the biophysical effects on VSD activation, PGD opening and VSD-PGD coupling. These results reveal some common characteristics and mechanistic insights into KV channel modulation by TM β subunits.

  7. Voltage dependence of proton pumping by bacteriorhodopsin mutants with altered lifetime of the M intermediate.

    Directory of Open Access Journals (Sweden)

    Sven Geibel

    Full Text Available The light-driven proton pump bacteriorhodopsin (BR from Halobacterium salinarum is tightly regulated by the [H(+] gradient and transmembrane potential. BR exhibits optoelectric properties, since spectral changes during the photocycle are kinetically controlled by voltage, which predestines BR for optical storage or processing devices. BR mutants with prolonged lifetime of the blue-shifted M intermediate would be advantageous, but the optoelectric properties of such mutants are still elusive. Using expression in Xenopus oocytes and two-electrode voltage-clamping, we analyzed photocurrents of BR mutants with kinetically destabilized (F171C, F219L or stabilized (D96N, D96G M intermediate in response to green light (to probe H(+ pumping and blue laser flashes (to probe accumulation/decay of M. These mutants have divergent M lifetimes. As for BR-WT, this strictly correlates with the voltage dependence of H(+ pumping. BR-F171C and BR-F219L showed photocurrents similar to BR-WT. Yet, BR-F171C showed a weaker voltage dependence of proton pumping. For both mutants, blue laser flashes applied during and after green-light illumination showed reduced M accumulation and shorter M lifetime. In contrast, BR-D96G and BR-D96N exhibited small photocurrents, with nonlinear current-voltage curves, which increased strongly in the presence of azide. Blue laser flashes showed heavy M accumulation and prolonged M lifetime, which accounts for the strongly reduced H(+ pumping rate. Hyperpolarizing potentials augmented these effects. The combination of M-stabilizing and -destabilizing mutations in BR-D96G/F171C/F219L (BR-tri shows that disruption of the primary proton donor Asp-96 is fatal for BR as a proton pump. Mechanistically, M destabilizing mutations cannot compensate for the disruption of Asp-96. Accordingly, BR-tri and BR-D96G photocurrents were similar. However, BR-tri showed negative blue laser flash-induced currents even without actinic green light, indicating

  8. G Protein-induced Trafficking of Voltage-dependent Calcium Channels

    National Research Council Canada - National Science Library

    Eugene Tombler; Nory Jun Cabanilla; Paul Carman; Natasha Permaul; John J. Hall; Ryan W. Richman; Jessica Lee; Jennifer Rodriguez; Dan P. Felsenfeld; Robert F. Hennigan; María A. Diversé-Pierluissi

    2006-01-01

    .... Here we report a novel mechanism for G protein-mediated modulation of neuronal voltage-dependent calcium channels that involves the destabilization and subsequent removal of calcium channels from the plasma membrane...

  9. Analytical Model for Voltage-Dependent Photo and Dark Currents in Bulk Heterojunction Organic Solar Cells

    OpenAIRE

    2016-01-01

    A physics-based explicit mathematical model for the external voltage-dependent forward dark current in bulk heterojunction (BHJ) organic solar cells is developed by considering Shockley-Read-Hall (SRH) recombination and solving the continuity equations for both electrons and holes. An analytical model for the external voltage-dependent photocurrent in BHJ organic solar cells is also proposed by incorporating exponential photon absorption, dissociation efficiency of bound electron-hole pairs (...

  10. Pharmacology of the human red cell voltage-dependent cation channel Part I. Activation by clotrimazole and analogues

    DEFF Research Database (Denmark)

    Barksmann, Trine Lyberth; Kristensen, Berit I.; Christophersen, Palle.

    2004-01-01

    Human red cells, Nonselective voltage dependent cation channel, NSVDC channel, Gárdos channel blockers, NSVDC channel activators......Human red cells, Nonselective voltage dependent cation channel, NSVDC channel, Gárdos channel blockers, NSVDC channel activators...

  11. Dynamics of a two-level system under strong driving: Quantum-gate optimization based on Floquet theory

    Science.gov (United States)

    Deng, Chunqing; Shen, Feiruo; Ashhab, Sahel; Lupascu, Adrian

    2016-09-01

    We consider the dynamics of a two-level system (qubit) driven by strong and short resonant pulses in the framework of Floquet theory. First we derive analytical expressions for the quasienergies and Floquet states of the driven system. If the pulse amplitude varies very slowly, the system adiabatically follows the instantaneous Floquet states, which acquire dynamical phases that depend on the evolution of the quasienergies over time. The difference between the phases acquired by the two Floquet states corresponds to a qubit state rotation, generalizing the notion of Rabi oscillations to the case of large driving amplitudes. If the pulse amplitude changes very fast, the evolution is nonadiabatic, with transitions taking place between the Floquet states. We quantify and analyze the nonadiabatic transitions during the pulse by employing adiabatic perturbation theory and exact numerical simulations. We find that, for certain combinations of pulse rise and fall times and maximum driving amplitude, a destructive interference effect leads to a remarkably strong suppression of transitions between the Floquet states. This effect provides the basis of a quantum control protocol, which we name Floquet interference efficient suppression of transitions in the adiabatic basis (FIESTA), that can be used to design ultrafast high-fidelity single-qubit quantum gates.

  12. Strong Coupling Cavity QED with Gate-Defined Double Quantum Dots Enabled by a High Impedance Resonator

    Directory of Open Access Journals (Sweden)

    A. Stockklauser

    2017-03-01

    Full Text Available The strong coupling limit of cavity quantum electrodynamics (QED implies the capability of a matterlike quantum system to coherently transform an individual excitation into a single photon within a resonant structure. This not only enables essential processes required for quantum information processing but also allows for fundamental studies of matter-light interaction. In this work, we demonstrate strong coupling between the charge degree of freedom in a gate-defined GaAs double quantum dot (DQD and a frequency-tunable high impedance resonator realized using an array of superconducting quantum interference devices. In the resonant regime, we resolve the vacuum Rabi mode splitting of size 2g/2π=238  MHz at a resonator linewidth κ/2π=12  MHz and a DQD charge qubit decoherence rate of γ_{2}/2π=40  MHz extracted independently from microwave spectroscopy in the dispersive regime. Our measurements indicate a viable path towards using circuit-based cavity QED for quantum information processing in semiconductor nanostructures.

  13. Extracellular Linkers Completely Transplant the Voltage Dependence from Kv1.2 Ion Channels to Kv2.1.

    Science.gov (United States)

    Elinder, Fredrik; Madeja, Michael; Zeberg, Hugo; Århem, Peter

    2016-10-18

    The transmembrane voltage needed to open different voltage-gated K (Kv) channels differs by up to 50 mV from each other. In this study we test the hypothesis that the channels' voltage dependences to a large extent are set by charged amino-acid residues of the extracellular linkers of the Kv channels, which electrostatically affect the charged amino-acid residues of the voltage sensor S4. Extracellular cations shift the conductance-versus-voltage curve, G(V), by interfering with these extracellular charges. We have explored these issues by analyzing the effects of the divalent strontium ion (Sr(2+)) on the voltage dependence of the G(V) curves of wild-type and chimeric Kv channels expressed in Xenopus oocytes, using the voltage-clamp technique. Out of seven Kv channels, Kv1.2 was found to be most sensitive to Sr(2+) (50 mM shifted G(V) by +21.7 mV), and Kv2.1 to be the least sensitive (+7.8 mV). Experiments on 25 chimeras, constructed from Kv1.2 and Kv2.1, showed that the large Sr(2+)-induced G(V) shift of Kv1.2 can be transferred to Kv2.1 by exchanging the extracellular linker between S3 and S4 (L3/4) in combination with either the extracellular linker between S5 and the pore (L5/P) or that between the pore and S6 (LP/6). The effects of the linker substitutions were nonadditive, suggesting specific structural interactions. The free energy of these interactions was ∼20 kJ/mol, suggesting involvement of hydrophobic interactions and/or hydrogen bonds. Using principles from double-layer theory we derived an approximate linear equation (relating the voltage shifts to altered ionic strength), which proved to well match experimental data, suggesting that Sr(2+) acts on these channels mainly by screening surface charges. Taken together, these results highlight the extracellular surface potential at the voltage sensor as an important determinant of the channels' voltage dependence, making the extracellular linkers essential targets for evolutionary selection.

  14. Vector spin modeling for magnetic tunnel junctions with voltage dependent effects

    Energy Technology Data Exchange (ETDEWEB)

    Manipatruni, Sasikanth, E-mail: sasikanth.manipatruni@intel.com; Nikonov, Dmitri E.; Young, Ian A. [Exploratory Integrated Circuits, Components Research, Intel Corp., Hillsboro, Oregon 97124 (United States)

    2014-05-07

    Integration and co-design of CMOS and spin transfer devices requires accurate vector spin conduction modeling of magnetic tunnel junction (MTJ) devices. A physically realistic model of the MTJ should comprehend the spin torque dynamics of nanomagnet interacting with an injected vector spin current and the voltage dependent spin torque. Vector spin modeling allows for calculation of 3 component spin currents and potentials along with the charge currents/potentials in non-collinear magnetic systems. Here, we show 4-component vector spin conduction modeling of magnetic tunnel junction devices coupled with spin transfer torque in the nanomagnet. Nanomagnet dynamics, voltage dependent spin transport, and thermal noise are comprehended in a self-consistent fashion. We show comparison of the model with experimental magnetoresistance (MR) of MTJs and voltage degradation of MR with voltage. Proposed model enables MTJ circuit design that comprehends voltage dependent spin torque effects, switching error rates, spin degradation, and back hopping effects.

  15. Novel expression and regulation of voltage-dependent potassium channels in placentas from women with preeclampsia.

    Science.gov (United States)

    Mistry, Hiten D; McCallum, Laura A; Kurlak, Lesia O; Greenwood, Iain A; Broughton Pipkin, Fiona; Tribe, Rachel M

    2011-09-01

    Preeclampsia is associated with structural/functional alterations in placental and maternal vasculature. Voltage-dependant potassium channels encoded by KCNQ1-5 genes have been detected in several types of blood vessels where they promote vascular relaxation. Voltage-dependant potassium channel function can be modulated by KCNE1-5-encoded accessory proteins. The aim of this study was to determine whether KCNQ and KCNE genes are differentially expressed in placentas from women with preeclampsia compared with normotensive controls and to examine any differences in those who delivered preterm (voltage-dependant potassium channels are expressed and markedly modulated in placentas from preeclamptic women. Differential expression of isoforms may lead to altered cell proliferation. The correlation between KCNQ3 and KCNE5 expression is indicative of a novel channel complex and warrants further investigation.

  16. Single electron charge sensitivity of liquid-gated carbon nanotube transistors.

    Science.gov (United States)

    Sharf, Tal; Wang, Neng-Ping; Kevek, Joshua W; Brown, Morgan A; Wilson, Heather; Heinze, Stefan; Minot, Ethan D

    2014-09-10

    Random telegraph signals corresponding to activated charge traps were observed with liquid-gated CNT FETs. The high signal-to-noise ratio that we observe demonstrates that single electron charge sensing is possible with CNT FETs in liquids at room temperature. We have characterized the gate-voltage dependence of the random telegraph signals and compared to theoretical predictions. The gate-voltage dependence clearly identifies the sign of the activated trapped charge.

  17. Poly(ethylene glycol-cholesterol inhibits L-type Ca2+ channel currents and augments voltage-dependent inactivation in A7r5 cells.

    Directory of Open Access Journals (Sweden)

    Rikuo Ochi

    Full Text Available Cholesterol distributes at a high density in the membrane lipid raft and modulates ion channel currents. Poly(ethylene glycol cholesteryl ether (PEG-cholesterol is a nonionic amphipathic lipid consisting of lipophilic cholesterol and covalently bound hydrophilic PEG. PEG-cholesterol is used to formulate lipoplexes to transfect cultured cells, and liposomes for encapsulated drug delivery. PEG-cholesterol is dissolved in the external leaflet of the lipid bilayer, and expands it to flatten the caveolae and widen the gap between the two leaflets. We studied the effect of PEG-cholesterol on whole cell L-type Ca(2+ channel currents (I(Ca,L recorded from cultured A7r5 arterial smooth muscle cells. The pretreatment of cells with PEG-cholesterol decreased the density of ICa,L and augmented the voltage-dependent inactivation with acceleration of time course of inactivation and negative shift of steady-state inactivation curve. Methyl-β-cyclodextrin (MβCD is a cholesterol-binding oligosaccharide. The enrichment of cholesterol by the MβCD:cholesterol complex (cholesterol (MβCD caused inhibition of I(Ca,L but did not augment voltage-dependent inactivation. Incubation with MβCD increased I(Ca,L, slowed the time course of inactivation and shifted the inactivation curve to a positive direction. Additional pretreatment by a high concentration of MβCD of the cells initially pretreated with PEG-cholesterol, increased I(Ca,L to a greater level than the control, and removed the augmented voltage-dependent inactivation. Due to the enhancement of the voltage-dependent inactivation, PEG-cholesterol inhibited window I(Ca,L more strongly as compared with cholesterol (MβCD. Poly(ethylene glycol conferred to cholesterol the efficacy to induce sustained augmentation of voltage-dependent inactivation of I(Ca,L.

  18. Electrolyte-gated charge transport in molecularly linked gold nanoparticle films: The transition from a Mott insulator to an exotic metal with strong electron-electron interactions

    Science.gov (United States)

    Tie, M.; Dhirani, A.-A.

    2016-09-01

    Strong electron-electron interactions experienced by electrons as they delocalize are widely believed to play a key role in a range of remarkable phenomena such as high Tc superconductivity, colossal magnetoresistance, and others. Strongly correlated electrons are often described by the Hubbard model, which is the simplest description of a correlated system and captures important gross features of phase diagrams of strongly correlated materials. However, open challenges in this field include experimentally mapping correlated electron phenomena beyond those captured by the Hubbard model, and extending the model accordingly. Here we use electrolyte gating to study a metal-insulator transition (MIT) in a new class of strongly correlated material, namely, nanostructured materials, using 1,4-butanedithiol-linked Au nanoparticle films (NPFs) as an example. Electrolyte gating provides a means for tuning the chemical potential of the materials over a wide range, without significantly modifying film morphology. On the insulating side of the transition, we observe Efros-Shklovskii variable range hopping and a soft Coulomb gap, evidencing the importance of Coulomb barriers. On the metallic side of the transition, we observe signatures of strong disorder mediated electron-electron correlations. Gating films near MIT also reveal a zero-bias conductance peak, which we attribute to a resonance at the Fermi level predicted by the Hubbard and Anderson impurity models when electrons delocalize and experience strong Coulomb electron-electron interactions. This study shows that by enabling large changes in carrier density, electrolyte gating of Au NPFs is a powerful means for tuning through the Hubbard MIT in NPFs. By revealing the range of behaviours that strongly correlated electrons can exhibit, this platform can guide the development of an improved understanding of correlated materials.

  19. Eugenol dilates rat cerebral arteries by inhibiting smooth muscle cell voltage-dependent calcium channels.

    Science.gov (United States)

    Peixoto-Neves, Dieniffer; Leal-Cardoso, Jose Henrique; Jaggar, Jonathan H

    2014-11-01

    Plants high in eugenol, a phenylpropanoid compound, are used as folk medicines to alleviate diseases including hypertension. Eugenol has been demonstrated to relax conduit and ear arteries and reduce systemic blood pressure, but mechanisms involved are unclear. Here, we studied eugenol regulation of resistance-size cerebral arteries that control regional brain blood pressure and flow and investigated mechanisms involved. We demonstrate that eugenol dilates arteries constricted by either pressure or membrane depolarization (60 mM K) in a concentration-dependent manner. Experiments performed using patch-clamp electrophysiology demonstrated that eugenol inhibited voltage-dependent calcium (Ca) currents, when using Ba as a charge carrier, in isolated cerebral artery smooth muscle cells. Eugenol inhibition of voltage-dependent Ca currents involved pore block, a hyperpolarizing shift (∼-10 mV) in voltage-dependent inactivation, an increase in the proportion of steady-state inactivating current, and acceleration of inactivation rate. In summary, our data indicate that eugenol dilates cerebral arteries by means of multimodal inhibition of voltage-dependent Ca channels.

  20. Voltage-dependent currents in microvillar receptor cells of the frog vomeronasal organ.

    Science.gov (United States)

    Trotier, D; Døving, K B; Rosin, J F

    1993-08-01

    Vomeronasal receptor cells are differentiated bipolar neurons with a long dendrite bearing numerous microvilli. Isolated cells (with a mean dendritic length of 65 microns) and cells in mucosal slices were studied using whole-cell and Nystatin-perforated patch-clamp recordings. At rest, the membrane potential was -61 +/- 13 mV (mean +/- SD; n = 61). Sixty-four per cent of the cells had a resting potential in the range of -60 to -86 mV, with almost no spontaneous action potential. The input resistance was in the G omega range and overshooting repetitive action potentials were elicited by injecting depolarizing current pulses in the range of 2-10 pA. Voltage-dependent currents were characterized under voltage-clamp conditions. A transient fast inward current activating near -45 mV was blocked by tetrodotoxin. In isolated cells, it was half-deactivated at a membrane potential near -75 mV. An outward K+ current was blocked by internal Cs+ ions or by external tetraethylammonium or Ba2+ ions. A calcium-activated voltage-dependent potassium current was blocked by external Cd2+ ions. A voltage-dependent Ca2+ current was observed in an iso-osmotic BaCl2 solution. Finally, a hyperpolarization-activated inward current was recorded. Voltage-dependent currents in these microvillar olfactory receptor neurons appear qualitatively similar to those already described in ciliated olfactory receptor cells located in the principal olfactory epithelium.

  1. Correlation character of ionic current fluctuations: analysis of ion current through a voltage-dependent potassium single channel.

    Science.gov (United States)

    Tong-Han, Lan; Huang, Xi; Jia-Rui, Lin

    2005-10-03

    The gating of ion channels has widely been modeled by assuming the transition between open and closed states is a memoryless process. Nevertheless, the statistical analysis of an ionic current signal recorded from voltage dependence K(+) single channel is presented. Calculating the sample auto-correlation function of the ionic current based on the digitized signals, rather than the sequence of open and closed states duration time. The results provide evidence for the existence of memory. For different voltages, the ion channel current fluctuation has different correlation attributions. The correlations in data generated by simulation of two Markov models, on one hand, auto-correlation function of the ionic current shows a weaker memory, after a delayed period of time, the attribute of memory does not exist; on the other hand, the correlation depends on the number of states in the Markov model. For V(p)=-60 mV pipette potential, spectral analysis of ion channel current was conducted, the result indicates that the spectrum is not a flat spectrum, the data set from ionic current fluctuations shows considerable variability with a broad 1/f -like spectrum, alpha=1.261+/-0.24. Thus the ion current fluctuations give information about the kinetics of the channel protein, the results suggest the correlation character of ion channel protein nonlinear kinetics regardless of whether the channel is in open or closed state.

  2. Voltage-dependent motion of the catalytic region of voltage-sensing phosphatase monitored by a fluorescent amino acid.

    Science.gov (United States)

    Sakata, Souhei; Jinno, Yuka; Kawanabe, Akira; Okamura, Yasushi

    2016-07-05

    The cytoplasmic region of voltage-sensing phosphatase (VSP) derives the voltage dependence of its catalytic activity from coupling to a voltage sensor homologous to that of voltage-gated ion channels. To assess the conformational changes in the cytoplasmic region upon activation of the voltage sensor, we genetically incorporated a fluorescent unnatural amino acid, 3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (Anap), into the catalytic region of Ciona intestinalis VSP (Ci-VSP). Measurements of Anap fluorescence under voltage clamp in Xenopus oocytes revealed that the catalytic region assumes distinct conformations dependent on the degree of voltage-sensor activation. FRET analysis showed that the catalytic region remains situated beneath the plasma membrane, irrespective of the voltage level. Moreover, Anap fluorescence from a membrane-facing loop in the C2 domain showed a pattern reflecting substrate turnover. These results indicate that the voltage sensor regulates Ci-VSP catalytic activity by causing conformational changes in the entire catalytic region, without changing their distance from the plasma membrane.

  3. Mechanism of voltage-gated channel formation in lipid membranes.

    Science.gov (United States)

    Guidelli, Rolando; Becucci, Lucia

    2016-04-01

    Although several molecular models for voltage-gated ion channels in lipid membranes have been proposed, a detailed mechanism accounting for the salient features of experimental data is lacking. A general treatment accounting for peptide dipole orientation in the electric field and their nucleation and growth kinetics with ion channel formation is provided. This is the first treatment that explains all the main features of the experimental current-voltage curves of peptides forming voltage-gated channels available in the literature. It predicts a regime of weakly voltage-dependent conductance, followed by one of strong voltage-dependent conductance at higher voltages. It also predicts values of the parameters expressing the exponential dependence of conductance upon voltage and peptide bulk concentration for both regimes, in good agreement with those reported in the literature. Most importantly, the only two adjustable parameters involved in the kinetics of nucleation and growth of ion channels can be varied over broad ranges without affecting the above predictions to a significant extent. Thus, the fitting of experimental current-voltage curves stems naturally from the treatment and depends only slightly upon the choice of the kinetic parameters.

  4. Localization and pharmacological characterization of voltage dependent calcium channels in cultured neocortical neurons

    DEFF Research Database (Denmark)

    Timmermann, D B; Lund, T M; Belhage, B

    2001-01-01

    using the fluorescent calcium chelator fura-2. The types of calcium channels present at the synaptic terminal were determined by the inhibitory action of calcium channel blockers on potassium-induced [3H]GABA release in the same cell preparation. L-, N-, P-, Q- and R-/T-type voltage dependent calcium...... channels were differentially distributed in somata, neurites and nerve terminals. omega-conotoxin MVIIC (omega-CgTx MVIIC) inhibited approximately 40% of the Ca(2+)-rise in both somata and neurites and 60% of the potassium induced [3H]GABA release, indicating that the Q-type channel is the quantitatively...... in cytosolic calcium concentration. The results of this investigation demonstrate that pharmacologically distinct types of voltage dependent calcium channels are differentially localized in cell bodies, neurites and nerve terminals of mouse cortical neurons but that the Q-type calcium channel appears...

  5. Lavender Oil-Potent Anxiolytic Properties via Modulating Voltage Dependent Calcium Channels

    OpenAIRE

    2013-01-01

    Recent clinical data support the clinical use of oral lavender oil in patients suffering from subsyndromal anxiety. We identified the molecular mechanism of action that will alter the perception of lavender oil as a nonspecific ingredient of aromatherapy to a potent anxiolytic inhibiting voltage dependent calcium channels (VOCCs) as highly selective drug target. In contrast to previous publications where exorbitant high concentrations were used, the effects of lavender oil in behavioral, bioc...

  6. A comparative study of the action of tolperisone on seven different voltage dependent sodium channel isoforms.

    Science.gov (United States)

    Hofer, Doris; Lohberger, Birgit; Steinecker, Bibiane; Schmidt, Kurt; Quasthoff, Stefan; Schreibmayer, Wolfgang

    2006-05-24

    The specific, acute interaction of tolperisone, an agent used as a muscle relaxant and for the treatment of chronic pain conditions, with the Na(v1.2), Na(v1.3), Na(v1.4), Na(v1.5), Na(v1.6), Na(v1.7), and Na(v1.8) isoforms of voltage dependent sodium channels was investigated and compared to that of lidocaine. Voltage dependent sodium channels were expressed in the Xenopus laevis oocyte expression system and sodium currents were recorded with the two electrode voltage clamp technique. Cumulative dose response relations revealed marked differences in IC(50) values between the two drugs on identical isoforms, as well as between isoforms. A detailed kinetic analysis uncovered that tolperisone as well as lidocaine exhibited their blocking action not only via state dependent association/dissociation with voltage dependent sodium channels, but a considerable fraction of inhibition is tonic, i.e. permanent and basic in nature. Voltage dependent activation was affected to a minor extent only. A shift in steady-state inactivation to more negative potentials could be observed for most drug/isoform combinations. The contribution of this shift to overall block was, however, small at drug concentrations resulting in considerable overall block. Recovery from inactivation was affected notably by both drugs. Lidocaine application led to a pronounced prolongation of the time constant of the fast recovery process for the Na(v1.3), Na(v1.5), and Na(v1.7) isoforms, indicating common structural properties in the local anesthetic receptor site of these three proteins. Interestingly, this characteristic drug action was not observed for tolperisone.

  7. Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes.

    Science.gov (United States)

    Rubi, Lena; Gawali, Vaibhavkumar S; Kubista, Helmut; Todt, Hannes; Hilber, Karlheinz; Koenig, Xaver

    2015-01-01

    Dysferlin plays a decisive role in calcium-dependent membrane repair in myocytes. Mutations in the encoding DYSF gene cause a number of myopathies, e.g. limb-girdle muscular dystrophy type 2B (LGMD2B). Besides skeletal muscle degenerative processes, dysferlin deficiency is also associated with cardiac complications. Thus, both LGMD2B patients and dysferlin-deficient mice develop a dilated cardiomyopathy. We and others have recently reported that dystrophin-deficient ventricular cardiomyocytes from mouse models of Duchenne muscular dystrophy show significant abnormalities in voltage-dependent ion channels, which may contribute to the pathophysiology in dystrophic cardiomyopathy. The aim of the present study was to investigate if dysferlin, like dystrophin, is a regulator of cardiac ion channels. By using the whole cell patch-clamp technique, we compared the properties of voltage-dependent calcium and sodium channels, as well as action potentials in ventricular cardiomyocytes isolated from the hearts of normal and dysferlin-deficient (dysf) mice. In contrast to dystrophin deficiency, the lack of dysferlin did not impair the ion channel properties and left action potential parameters unaltered. In connection with normal ECGs in dysf mice these results suggest that dysferlin deficiency does not perturb cardiac electrophysiology. Our study demonstrates that dysferlin does not regulate cardiac voltage-dependent ion channels, and implies that abnormalities in cardiac ion channels are not a universal characteristic of all muscular dystrophy types. © 2015 S. Karger AG, Basel.

  8. Development of voltage-dependent calcium, sodium, and potassium currents in Xenopus spinal neurons.

    Science.gov (United States)

    O'Dowd, D K; Ribera, A B; Spitzer, N C

    1988-03-01

    Action potentials of embryonic nerve and muscle cells often have a different ionic dependence and longer duration than those of mature cells. The action potential of spinal cord neurons from Xenopus laevis exhibits a prominent calcium component at early stages of development that diminishes with age as the impulse becomes principally sodium dependent. Whole-cell voltage-clamp analysis has been undertaken to characterize the changes in membrane currents during development of these neurons in culture. Four voltage-dependent currents of cells were identified and examined during the first day in vitro, when most of the change in the action potential occurs. There are no changes in the peak density of the calcium current (ICa), its voltage dependence, or time to half-maximal activation; a small increase in inactivation is apparent. The major change in sodium current (INa) is a 2-fold increase in its density. In addition, more subtle changes in the kinetics of the macroscopic sodium current were noted. The peak density of voltage-dependent potassium current (IKv) increases 3-fold, and this current becomes activated almost twice as fast. No changes were noted in the extent of its inactivation. The calcium-dependent potassium current (IKc) consists of an inactivating and a sustained component. The former increases 2-fold in peak current density, and the latter increases similarly at less depolarized voltages. The changes in these currents contribute to the decrease in duration and the change in ionic dependence of the impulse.

  9. Voltage dependence of Na translocation by the Na/K pump.

    Science.gov (United States)

    Nakao, M; Gadsby, D C

    During each complete reaction cycle, the Na/K pump transports three Na ions out across the cell membrane and two K ions in. The resulting net extrusion of positive charge generates outward membrane current but, until now, it was unclear how that net charge movement occurs. Reasonable possibilities included a single positive charge moving outwards during Na translocation; or a single negative charge moving inwards during K translocation; or either positive or negative charges moving during both translocation steps, but in unequal quantities. Any step that involves net charge movement through the membrane must have voltage-dependent transition rates. Here we report measurements of transient, voltage-dependent, displacement currents generated by the pump when its normal Na/K transport cycle has been interrupted by removal of external K and it is thus constrained to carry out Na/Na exchange. The quantity and voltage sensitivity of the charge moved during these transient currents suggests that Na translocation includes a voltage-dependent transition involving movement of one positive charge across the membrane. This single step can thus fully account for the electrogenic nature of Na/K exchange. The result provides important new insight into the molecular mechanism of active cation transport.

  10. Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Lena Rubi

    2015-06-01

    Full Text Available Background/Aims: Dysferlin plays a decisive role in calcium-dependent membrane repair in myocytes. Mutations in the encoding DYSF gene cause a number of myopathies, e.g. limb-girdle muscular dystrophy type 2B (LGMD2B. Besides skeletal muscle degenerative processes, dysferlin deficiency is also associated with cardiac complications. Thus, both LGMD2B patients and dysferlin-deficient mice develop a dilated cardiomyopathy. We and others have recently reported that dystrophin-deficient ventricular cardiomyocytes from mouse models of Duchenne muscular dystrophy show significant abnormalities in voltage-dependent ion channels, which may contribute to the pathophysiology in dystrophic cardiomyopathy. The aim of the present study was to investigate if dysferlin, like dystrophin, is a regulator of cardiac ion channels. Methods and Results: By using the whole cell patch-clamp technique, we compared the properties of voltage-dependent calcium and sodium channels, as well as action potentials in ventricular cardiomyocytes isolated from the hearts of normal and dysferlin-deficient (dysf mice. In contrast to dystrophin deficiency, the lack of dysferlin did not impair the ion channel properties and left action potential parameters unaltered. In connection with normal ECGs in dysf mice these results suggest that dysferlin deficiency does not perturb cardiac electrophysiology. Conclusion: Our study demonstrates that dysferlin does not regulate cardiac voltage-dependent ion channels, and implies that abnormalities in cardiac ion channels are not a universal characteristic of all muscular dystrophy types.

  11. Voltage-gated lipid ion channels

    DEFF Research Database (Denmark)

    Blicher, Andreas; Heimburg, Thomas Rainer

    2013-01-01

    Synthetic lipid membranes can display channel-like ion conduction events even in the absence of proteins. We show here that these events are voltage-gated with a quadratic voltage dependence as expected from electrostatic theory of capacitors. To this end, we recorded channel traces and current...

  12. "Slow" Voltage-Dependent Inactivation of CaV2.2 Calcium Channels Is Modulated by the PKC Activator Phorbol 12-Myristate 13-Acetate (PMA.

    Directory of Open Access Journals (Sweden)

    Lei Zhu

    Full Text Available CaV2.2 (N-type voltage-gated calcium channels (Ca2+ channels play key roles in neurons and neuroendocrine cells including the control of cellular excitability, neurotransmitter / hormone secretion, and gene expression. Calcium entry is precisely controlled by channel gating properties including multiple forms of inactivation. "Fast" voltage-dependent inactivation is relatively well-characterized and occurs over the tens-to- hundreds of milliseconds timeframe. Superimposed on this is the molecularly distinct, but poorly understood process of "slow" voltage-dependent inactivation, which develops / recovers over seconds-to-minutes. Protein kinases can modulate "slow" inactivation of sodium channels, but little is known about if/how second messengers control "slow" inactivation of Ca2+ channels. We investigated this using recombinant CaV2.2 channels expressed in HEK293 cells and native CaV2 channels endogenously expressed in adrenal chromaffin cells. The PKC activator phorbol 12-myristate 13-acetate (PMA dramatically prolonged recovery from "slow" inactivation, but an inactive control (4α-PMA had no effect. This effect of PMA was prevented by calphostin C, which targets the C1-domain on PKC, but only partially reduced by inhibitors that target the catalytic domain of PKC. The subtype of the channel β-subunit altered the kinetics of inactivation but not the magnitude of slowing produced by PMA. Intracellular GDP-β-S reduced the effect of PMA suggesting a role for G proteins in modulating "slow" inactivation. We postulate that the kinetics of recovery from "slow" inactivation could provide a molecular memory of recent cellular activity and help control CaV2 channel availability, electrical excitability, and neurotransmission in the seconds-to-minutes timeframe.

  13. Charged residues distribution modulates selectivity of the open state of human isoforms of the voltage dependent anion-selective channel.

    Science.gov (United States)

    Amodeo, Giuseppe Federico; Scorciapino, Mariano Andrea; Messina, Angela; De Pinto, Vito; Ceccarelli, Matteo

    2014-01-01

    Voltage Dependent Anion-selective Channels (VDACs) are pore-forming proteins located in the outer mitochondrial membrane. They are responsible for the access of ions and energetic metabolites into the inner membrane transport systems. Three VDAC isoforms exist in mammalian, but their specific role is unknown. In this work we have performed extensive (overall ∼5 µs) Molecular Dynamics (MD) simulations of the human VDAC isoforms to detect structural and conformational variations among them, possibly related to specific functional roles of these proteins. Secondary structure analysis of the N-terminal domain shows a high similarity among the three human isoforms of VDAC but with a different plasticity. In particular, the N-terminal domain of the hVDAC1 is characterized by a higher plasticity, with a ∼20% occurrence for the 'unstructured' conformation throughout the folded segment, while hVDAC2, containing a peculiar extension of 11 amino acids at the N-terminal end, presents an additional 310-helical folded portion comprising residues 10' to 3, adhering to the barrel wall. The N-terminal sequences of hVDAC isoforms are predicted to have a low flexibility, with possible consequences in the dynamics of the human VDACs. Clear differences were found between hVDAC1 and hVDAC3 against hVDAC2: a significantly modified dynamics with possible important consequence on the voltage-gating mechanism. Charge distribution inside and at the mouth of the pore is responsible for a different preferential localization of ions with opposite charge and provide a valuable rationale for hVDAC1 and hVDAC3 having a Cl-/K+ selectivity ratio of 1.8, whereas hVDAC2 of 1.4. Our conclusion is that hVDAC isoforms, despite sharing a similar scaffold, have modified working features and a biological work is now requested to give evidence to the described dissimilarities.

  14. Purification and Characterization of Two Voltage-Dependent Anion Channel Isoforms from Plant Seeds1

    Science.gov (United States)

    Abrecht, Helge; Wattiez, Ruddy; Ruysschaert, Jean-Marie; Homblé, Fabrice

    2000-01-01

    Mitochondria were isolated from imbibed seeds of lentil (Lens culinaris) and Phaseolus vulgaris. We copurified two voltage-dependent anion channel from detergent solubilized mitochondria in a single purification step using hydroxyapatite. The two isoforms from P. vulgaris were separated by chromatofocusing chromatography in 4 m urea without any loss of channel activity. Channel activity of each isoform was characterized upon reconstitution into diphytanoyl phosphatidylcholine planar lipid bilayers. Both isoforms form large conductance channels that are slightly anion selective and display cation selective substates. PMID:11080295

  15. Admittance Spectroscopy in CZTSSe: Metastability Behavior and Voltage Dependent Defect Study

    Energy Technology Data Exchange (ETDEWEB)

    Koeper, Mark J.; Hages, Charles J.; Li, Jian V.; Levi, Dean; Agrawal, Rakesh

    2016-11-21

    Admittance spectroscopy has been performed on a CZTSSe device with a carrier injection pretreatment and under electronically relaxed conditions to demonstrate metastability behavior. We show that the measurements with the carrier injection pretreatment demonstrate two admittance signatures while the relaxed measurement demonstrates only one admittance signature with a different activation energy. Additionally, voltage dependent admittance spectroscopy was performed using the carrier injection pretreatment method at each of the applied voltage bias. The activation energies of the two admittance signatures were calculated and are shown to be independent of the voltage bias.

  16. Electron Spin Resonance Study of Organic Interfaces in Ion Gel-Gated Rubrene Single-Crystal Transistors

    Science.gov (United States)

    Takahashi, Yuki; Tsuji, Masaki; Yomogida, Yohei; Takenobu, Taishi; Iwasa, Yoshihiro; Marumoto, Kazuhiro

    2013-04-01

    Organic interfaces of rubrene single crystals (RSCs) in ion gel-gated electric double-layer transistors (EDLTs) were investigated by electron spin resonance (ESR). The EDLTs were fabricated by laminating ion-gel films onto RSCs. Clear ESR signals due to field-injected holes in RSCs were successfully observed at low gate voltages, showing a high spin concentration due to the high capacitance of EDLTs. The analyses of anisotropic ESR signals and its gate-voltage dependence show that the bulk molecular orientation at RSCs' interfaces is preserved without forming deep trapping levels, which demonstrate that organic interfaces in RSC-EDLTs are clean and undamaged under a strong electric field in EDLTs.

  17. Analytical Model for Voltage-Dependent Photo and Dark Currents in Bulk Heterojunction Organic Solar Cells

    Directory of Open Access Journals (Sweden)

    Mesbahus Saleheen

    2016-05-01

    Full Text Available A physics-based explicit mathematical model for the external voltage-dependent forward dark current in bulk heterojunction (BHJ organic solar cells is developed by considering Shockley-Read-Hall (SRH recombination and solving the continuity equations for both electrons and holes. An analytical model for the external voltage-dependent photocurrent in BHJ organic solar cells is also proposed by incorporating exponential photon absorption, dissociation efficiency of bound electron-hole pairs (EHPs, carrier trapping, and carrier drift and diffusion in the photon absorption layer. Modified Braun’s model is used to compute the electric field-dependent dissociation efficiency of the bound EHPs. The overall net current is calculated considering the actual solar spectrum. The mathematical models are verified by comparing the model calculations with various published experimental results. We analyze the effects of the contact properties, blend compositions, charge carrier transport properties (carrier mobility and lifetime, and cell design on the current-voltage characteristics. The power conversion efficiency of BHJ organic solar cells mostly depends on electron transport properties of the acceptor layer. The results of this paper indicate that improvement of charge carrier transport (both mobility and lifetime and dissociation of bound EHPs in organic blend are critically important to increase the power conversion efficiency of the BHJ solar cells.

  18. Cellular elements for seeing in the dark: voltage-dependent conductances in cockroach photoreceptors

    Directory of Open Access Journals (Sweden)

    Salmela Iikka

    2012-08-01

    Full Text Available Abstract Background The importance of voltage-dependent conductances in sensory information processing is well-established in insect photoreceptors. Here we present the characterization of electrical properties in photoreceptors of the cockroach (Periplaneta americana, a nocturnal insect with a visual system adapted for dim light. Results Whole-cell patch-clamped photoreceptors had high capacitances and input resistances, indicating large photosensitive rhabdomeres suitable for efficient photon capture and amplification of small photocurrents at low light levels. Two voltage-dependent potassium conductances were found in the photoreceptors: a delayed rectifier type (KDR and a fast transient inactivating type (KA. Activation of KDR occurred during physiological voltage responses induced by light stimulation, whereas KA was nearly fully inactivated already at the dark resting potential. In addition, hyperpolarization of photoreceptors activated a small-amplitude inward-rectifying (IR current mediated at least partially by chloride. Computer simulations showed that KDR shapes light responses by opposing the light-induced depolarization and speeding up the membrane time constant, whereas KA and IR have a negligible role in the majority of cells. However, larger KA conductances were found in smaller and rapidly adapting photoreceptors, where KA could have a functional role. Conclusions The relative expression of KA and KDR in cockroach photoreceptors was opposite to the previously hypothesized framework for dark-active insects, necessitating further comparative work on the conductances. In general, the varying deployment of stereotypical K+ conductances in insect photoreceptors highlights their functional flexibility in neural coding.

  19. Voltage dependence of rate functions for Na+ channel inactivation within a membrane

    CERN Document Server

    Vaccaro, Samuel R

    2015-01-01

    The inactivation of a Na+ channel occurs when the activation of the charged S4 segment of domain IV, with rate functions $\\alpha_{i}$ and $\\beta_{i}$, is followed by the binding of an intracellular hydrophobic motif which blocks conduction through the ion pore, with rate functions $\\gamma_{i}$ and $\\delta_{i}$. During a voltage clamp of the Na+ channel, the solution of the master equation for inactivation reduces to the relaxation of a rate equation when the binding of the inactivation motif is rate limiting ($\\alpha_{i} \\gg \\gamma_{i}$ and $\\beta_{i} \\gg \\delta_{i}$). The voltage dependence of the derived forward rate function for Na+ channel inactivation has an exponential dependence on the membrane potential for small depolarizations and approaches a constant value for larger depolarizations, whereas the voltage dependence of the backward rate function is exponential, and each rate has a similar form to the Hodgkin-Huxley empirical rate functions for Na+ channel inactivation in the squid axon.

  20. Voltage-dependent K+ currents contribute to heterogeneity of olfactory ensheathing cells

    Science.gov (United States)

    Rela, Lorena; Piantanida, Ana Paula; Bordey, Angelique; Greer, Charles A.

    2015-01-01

    The olfactory nerve is permissive for axon growth throughout life. This has been attributed in part to the olfactory ensheathing glial cells that encompass the olfactory sensory neuron fascicles. Olfactory ensheathing cells also promote axon growth in vitro and when transplanted in vivo to sites of injury. The mechanisms involved remain largely unidentified owing in part to the limited knowledge of the physiological properties of ensheathing cells. Glial cells rely for many functions on the properties of the potassium channels expressed; however, those expressed in ensheathing cells are unknown. Here we show that olfactory ensheathing cells express voltage-dependent potassium currents compatible with inward rectifier (Kir) and delayed rectifier (KDR) channels. Together with gap junction coupling, these contribute to the heterogeneity of membrane properties observed in olfactory ensheathing cells. The relevance of K+ currents expressed by ensheathing cells is discussed in relation to plasticity of the olfactory nerve. PMID:25856239

  1. Selective modulation of cellular voltage dependent calcium channels by hyperbaric pressure - a suggested HPNS partial mechanism

    Directory of Open Access Journals (Sweden)

    Ben eAviner

    2014-05-01

    Full Text Available Professional deep sea divers experience motor and cognitive impairment, known as High Pressure Neurological Syndrome (HPNS, when exposed to pressures of 100 msw (1.1MPa and above, considered to be the result of synaptic transmission alteration. Previous studies have indicated modulation of presynaptic Ca2+ currents at high pressure. We directly measured for the first time pressure effects on the currents of voltage dependent Ca2+ channels (VDCCs expressed in Xenopus oocytes. Pressure selectivity augmented the current in CaV1.2 and depressed it in CaV3.2 channels. Pressure application also affected the channels' kinetics, such as ƮRise, ƮDecay. Pressure modulation of VDCCs seems to play an important role in generation of HPNS signs and symptoms.

  2. G protein-induced trafficking of voltage-dependent calcium channels.

    Science.gov (United States)

    Tombler, Eugene; Cabanilla, Nory Jun; Carman, Paul; Permaul, Natasha; Hall, John J; Richman, Ryan W; Lee, Jessica; Rodriguez, Jennifer; Felsenfeld, Dan P; Hennigan, Robert F; Diversé-Pierluissi, María A

    2006-01-20

    Calcium channels are well known targets for inhibition by G protein-coupled receptors, and multiple forms of inhibition have been described. Here we report a novel mechanism for G protein-mediated modulation of neuronal voltage-dependent calcium channels that involves the destabilization and subsequent removal of calcium channels from the plasma membrane. Imaging experiments in living sensory neurons show that, within seconds of receptor activation, calcium channels are cleared from the membrane and sequestered in clathrin-coated vesicles. Disruption of the L1-CAM-ankyrin B complex with the calcium channel mimics transmitter-induced trafficking of the channels, reduces calcium influx, and decreases exocytosis. Our results suggest that G protein-induced removal of plasma membrane calcium channels is a consequence of disrupting channel-cytoskeleton interactions and might represent a novel mechanism of presynaptic inhibition.

  3. Rab3 interacting molecule 3 mutations associated with autism alter regulation of voltage-dependent Ca²⁺ channels.

    Science.gov (United States)

    Takada, Yoshinori; Hirano, Mitsuru; Kiyonaka, Shigeki; Ueda, Yoshifumi; Yamaguchi, Kazuma; Nakahara, Keiko; Mori, Masayuki X; Mori, Yasuo

    2015-09-01

    Autism is a neurodevelopmental psychiatric disorder characterized by impaired reciprocal social interaction, disrupted communication, and restricted and stereotyped patterns of interests. Autism is known to have a strong genetic component. Although mutations in several genes account for only a small proportion of individuals with autism, they provide insight into potential biological mechanisms that underlie autism, such as dysfunction in Ca(2+) signaling, synaptic dysfunction, and abnormal brain connectivity. In autism patients, two mutations have been reported in the Rab3 interacting molecule 3 (RIM3) gene. We have previously demonstrated that RIM3 physically and functionally interacts with voltage-dependent Ca(2+) channels (VDCCs) expressed in neurons via the β subunits, and increases neurotransmitter release. Here, by introducing corresponding autism-associated mutations that replace glutamic acid residue 176 with alanine (E176A) and methionine residue 259 with valine (M259V) into the C2B domain of mouse RIM3, we demonstrate that both mutations partly cancel the suppressive RIM3 effect on voltage-dependent inactivation of Ba(2+) currents through P/Q-type CaV2.1 recombinantly expressed in HEK293 cells. In recombinant N-type CaV2.2 VDCCs, the attenuation of the suppressive RIM3 effect on voltage-dependent inactivation is conserved for M259V but not E176A. Slowing of activation speed of P/Q-type CaV2.1 currents by RIM3 is abolished in E176A, while the physical interaction between RIM3 and β subunits is significantly attenuated in M259V. Moreover, increases by RIM3 in depolarization-induced Ca(2+) influx and acetylcholine release are significantly attenuated by E176A in rat pheochromocytoma PC12 cells. Thus, our data raise the interesting possibility that autism phenotypes are elicited by synaptic dysfunction via altered regulation of presynaptic VDCC function and neurotransmitter release.

  4. Modeling hysteresis observed in the human erythrocyte voltage-dependent cation channel

    DEFF Research Database (Denmark)

    Flyvbjerg, Henrik; Gudowska-Nowak, Ewa; Christophersen, Palle

    2012-01-01

    cycle, including its direction, is reproduced by a model with 2×2 discrete states: the normal open/closed states and two different states of "gate tension". Rates of transitions between the two branches of the hysteresis curve are modeled with single-barrier kinetics by introducing a real......-valued "reaction coordinate" parametrizing the protein's conformational change between the two states of gate tension. The resulting scenario suggests a reanalysis of former experiments with NSVDC channels....

  5. Neutralization of Gating Charges in Domain II of the Sodium Channel α Subunit Enhances Voltage-Sensor Trapping by a β-Scorpion Toxin

    Science.gov (United States)

    Cestèle, Sandrine; Scheuer, Todd; Mantegazza, Massimo; Rochat, Hervé; Catterall, William A.

    2001-01-01

    β-Scorpion toxins shift the voltage dependence of activation of sodium channels to more negative membrane potentials, but only after a strong depolarizing prepulse to fully activate the channels. Their receptor site includes the S3–S4 loop at the extracellular end of the S4 voltage sensor in domain II of the α subunit. Here, we probe the role of gating charges in the IIS4 segment in β-scorpion toxin action by mutagenesis and functional analysis of the resulting mutant sodium channels. Neutralization of the positively charged amino acid residues in the IIS4 segment by mutation to glutamine shifts the voltage dependence of channel activation to more positive membrane potentials and reduces the steepness of voltage-dependent gating, which is consistent with the presumed role of these residues as gating charges. Surprisingly, neutralization of the gating charges at the outer end of the IIS4 segment by the mutations R850Q, R850C, R853Q, and R853C markedly enhances β-scorpion toxin action, whereas mutations R856Q, K859Q, and K862Q have no effect. In contrast to wild-type, the β-scorpion toxin Css IV causes a negative shift of the voltage dependence of activation of mutants R853Q and R853C without a depolarizing prepulse at holding potentials from −80 to −140 mV. Reaction of mutant R853C with 2-aminoethyl methanethiosulfonate causes a positive shift of the voltage dependence of activation and restores the requirement for a depolarizing prepulse for Css IV action. Enhancement of sodium channel activation by Css IV causes large tail currents upon repolarization, indicating slowed deactivation of the IIS4 voltage sensor by the bound toxin. Our results are consistent with a voltage-sensor–trapping model in which the β-scorpion toxin traps the IIS4 voltage sensor in its activated position as it moves outward in response to depolarization and holds it there, slowing its inward movement on deactivation and enhancing subsequent channel activation. Evidently

  6. Over Expression of Voltage Dependent Anion Channel 2 (VDAC2 in Muscles of Electrically Stunned Chickens

    Directory of Open Access Journals (Sweden)

    Norshahida Abu Samah, Azura Amid, and Faridah Yusof

    2011-12-01

    Full Text Available Water bath stunning is a common practice in commercial slaughterhouses. Such treatment is economic and in line with animal welfare practice. However, the conditions applied for the stunning process may vary from a slaughterhouse to another slaughterhouse. Such a loose regulation on the stunning procedure has opened up doors for food adulteration such as over dose stunning. In this study, a simple and reliable approach using proteomics have been developed to study the effect of different currents and voltages in stunning on the protein expression of the chickens. Protein profiles of the chickens were constructed in order to detect any differences in protein expression and modifications. The different voltage studied were 10 V, 40 V and 70 V while the values for current studied were 0.25 A, 0.5 A, and 0.75 A. After the proteomics analyses using 2D Platinum ImageMaster 6.0 and Matrix-assisted laser desorption ionization- time of flight (MALDI TOF spectrometry identification, Voltage dependent anion channel 2 (VDAC2 was identified to be over expressed in the muscle sample of over stunned chicken. The over expression of VDAC2 was confirmed at the transcriptional level of RNA expression. Real Time PCR showed that all over stunned samples contained higher mRNA expression level for VDAC2 genes. The mRNA level of VDAC2 was up-regulated by 59.87 fold change when normalized with housekeeping gene. In conclusion, VDAC2 could serve as potential biomarkers for identification of electrically stimulated chickens. The existence of these biomarkers will help to monitor the slaughtering and stunning process in the future. It will revolutionize the food authentication field and give a new breathe to the meat industry.ABSTRAK: Kaedah "waterbath stunning" merupakan amalan biasa di pusat-pusat penyembelihan. Kaedah ini adalah ekonomik dan selari dengan amalan kebajikan haiwan. Walaubagaimanapun, syarat-syarat yang digunakan untuk proses kejutan tersebut mungkin

  7. Functional coupling between large-conductance potassium channels and Cav3.2 voltage-dependent calcium channels participates in prostate cancer cell growth

    Directory of Open Access Journals (Sweden)

    Florian Gackière

    2013-07-01

    It is strongly suspected that potassium (K+ channels are involved in various aspects of prostate cancer development, such as cell growth. However, the molecular nature of those K+ channels implicated in prostate cancer cell proliferation and the mechanisms through which they control proliferation are still unknown. This study uses pharmacological, biophysical and molecular approaches to show that the main voltage-dependent K+ current in prostate cancer LNCaP cells is carried by large-conductance BK channels. Indeed, most of the voltage-dependent current was inhibited by inhibitors of BK channels (paxillin and iberiotoxin and by siRNA targeting BK channels. In addition, we reveal that BK channels constitute the main K+ channel family involved in setting the resting membrane potential in LNCaP cells at around −40 mV. This consequently promotes a constitutive calcium entry through T-type Cav3.2 calcium channels. We demonstrate, using single-channel recording, confocal imaging and co-immunoprecipitation approaches, that both channels form macromolecular complexes. Finally, using flow cytometry cell cycle measurements, cell survival assays and Ki67 immunofluorescent staining, we show that both BK and Cav3.2 channels participate in the proliferation of prostate cancer cells.

  8. Cortisone dissociates voltage-dependent K+ channel from its beta subunit

    Science.gov (United States)

    Pan, Yaping; Weng, Jun; Kabaleeswaran, Venkataraman; Li, Huiguang; Cao, Yu; Bhosle, Rahul C.; Zhou, Ming

    2009-01-01

    The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a wide variety of cells and essential for cellular excitability. In humans, loss-of-function mutations of Kv1 channels lead to hyperexcitability and are directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels assemble with beta subunits (Kvβ) and certain Kvβs, for example Kvβ1, have an N-terminal segment that closes a channel by the N-type inactivation mechanism. In principle dissociation of Kvβ1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases mammalian (rat) Kv1 channel activity by binding to Kvβ1. A crystal structure of the Kvβ-cortisone complex was solved to 1.82 Å resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kvβ. The new mode of channel modulation may be explored by native or synthetic ligands to fine tune cellular excitability. PMID:18806782

  9. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels.

    Science.gov (United States)

    Yagoda, Nicholas; von Rechenberg, Moritz; Zaganjor, Elma; Bauer, Andras J; Yang, Wan Seok; Fridman, Daniel J; Wolpaw, Adam J; Smukste, Inese; Peltier, John M; Boniface, J Jay; Smith, Richard; Lessnick, Stephen L; Sahasrabudhe, Sudhir; Stockwell, Brent R

    2007-06-14

    Therapeutics that discriminate between the genetic makeup of normal cells and tumour cells are valuable for treating and understanding cancer. Small molecules with oncogene-selective lethality may reveal novel functions of oncoproteins and enable the creation of more selective drugs. Here we describe the mechanism of action of the selective anti-tumour agent erastin, involving the RAS-RAF-MEK signalling pathway functioning in cell proliferation, differentiation and survival. Erastin exhibits greater lethality in human tumour cells harbouring mutations in the oncogenes HRAS, KRAS or BRAF. Using affinity purification and mass spectrometry, we discovered that erastin acts through mitochondrial voltage-dependent anion channels (VDACs)--a novel target for anti-cancer drugs. We show that erastin treatment of cells harbouring oncogenic RAS causes the appearance of oxidative species and subsequent death through an oxidative, non-apoptotic mechanism. RNA-interference-mediated knockdown of VDAC2 or VDAC3 caused resistance to erastin, implicating these two VDAC isoforms in the mechanism of action of erastin. Moreover, using purified mitochondria expressing a single VDAC isoform, we found that erastin alters the permeability of the outer mitochondrial membrane. Finally, using a radiolabelled analogue and a filter-binding assay, we show that erastin binds directly to VDAC2. These results demonstrate that ligands to VDAC proteins can induce non-apoptotic cell death selectively in some tumour cells harbouring activating mutations in the RAS-RAF-MEK pathway.

  10. Functional unit size of the neurotoxin receptors on the voltage-dependent sodium channel.

    Science.gov (United States)

    Angelides, K J; Nutter, T J; Elmer, L W; Kempner, E S

    1985-03-25

    Radiation inactivation was used in situ to determine the functional unit sizes of the neurotoxin receptors of the voltage-dependent sodium channel from rat brain. Frozen or lyophilized synaptosomes were irradiated with high energy electrons generated by a linear accelerator and assayed for [3H]saxitoxin, 125I-Leiurus quinquestriatus quinquestriatus (alpha-scorpion toxin), 125I-Centruroides suffusus suffusus (beta-scorpion toxin), and batrachotoxinin-A 20 alpha-[3H]benzoate binding activity. The functional unit size of the neurotoxin receptors determined in situ by target analysis are 220,000 for saxitoxin, 263,000 for alpha-scorpion toxin, and 45,000 for beta-scorpion toxin. Analysis of the inactivation curve for batrachotoxinin-A 20 alpha-benzoate binding to the channel yields two target sizes of Mr approximately 287,000 (50%) and approximately 51,000 (50%). The results are independent of the purity of the membrane preparation. Comparison of the radiation inactivation data with the protein composition of the rat brain sodium channel indicates that there are at least two functional components.

  11. Pharmacological Investigation of Voltage-dependent Ca2+ Channels in Human Ejaculatory Sperm in vitro

    Institute of Scientific and Technical Information of China (English)

    LI Lu; LIU Jihong; LI Jiagui; YE Zhangqun

    2006-01-01

    The types of the voltage-dependent calcium channels (VDCCs) in human ejaculatory sperm and the effects of calcium channel blocker (CCB) on human sperm motility parameters in vitro were investigated. The human sperm motility parameters in vitro in response to the pharmacological agents nifedipine (NIF, inhibitor of L-type VDCC) and ω-conotoxin (GVIA, inhibitor of N-type VDCC) were compared and analyzed statistically. The results showed that NIF (1, 5, 10 μmol/L)could not only significantly affect human sperm's shape but also spermatozoa motility after incubated at least 10 min in vitro (P<0.001). GVIA (0.1, 0.5 and 1 μmol/L) could just only significantly affect human sperm's progressive motility (a %+b %) after incubated for 20 min in vitro (P<0.01), but they both could not significantly affect spermic abnormality rate. It is suggested that L-type VDCC, non L-type VDCCs and isoform of L-type VDCC exist in the cell membrane of human sperm solely or together, and they participate in the spermic physiological processes especially the spermic motility.

  12. Voltage-dependent Ca2+ channel and Na+ channel in frog taste cells.

    Science.gov (United States)

    Kashiwayanagi, M; Miyake, M; Kurihara, K

    1983-01-01

    Frog taste cells were hyperpolarized by injecting an inward current pulse, and regenerative anode-break potentials were observed at the termination of the current pulse. The results obtained are as follows. 1) The magnitude of the anode-break potentials increased with the extent of hyperpolarization of taste cells and reached a saturation level around -200 mV. 2) The magnitudes of the anode-break potentials observed in 80 different taste cells hyperpolarized to about -200 mV were distributed widely from cell to cell. The average magnitude was 39 mV. 3) The anode-break potentials were recorded after the lingual artery was perfused with artificial solutions containing various channel blockers. The results indicated that the anode-break potentials are composed of Na+ and Ca2+ components. 4) The slope of the current-voltage relation obtained with cells hyperpolarized to 100 mV was appreciably decreased above -50 mV by application of tetrodotoxin to the perfusing solution. Discussion was made on possible roles of the voltage-dependent Na+ and Ca2+ channels in the electrotonic spreading of the depolarization at the receptor membranes to the synaptic area and in releasing a chemical transmitter.

  13. Regulation of mitochondrial function by voltage dependent anion channels in ethanol metabolism and the Warburg effect.

    Science.gov (United States)

    Lemasters, John J; Holmuhamedov, Ekhson L; Czerny, Christoph; Zhong, Zhi; Maldonado, Eduardo N

    2012-06-01

    Voltage dependent anion channels (VDAC) are highly conserved proteins that are responsible for permeability of the mitochondrial outer membrane to hydrophilic metabolites like ATP, ADP and respiratory substrates. Although previously assumed to remain open, VDAC closure is emerging as an important mechanism for regulation of global mitochondrial metabolism in apoptotic cells and also in cells that are not dying. During hepatic ethanol oxidation to acetaldehyde, VDAC closure suppresses exchange of mitochondrial metabolites, resulting in inhibition of ureagenesis. In vivo, VDAC closure after ethanol occurs coordinately with mitochondrial uncoupling. Since acetaldehyde passes through membranes independently of channels and transporters, VDAC closure and uncoupling together foster selective and more rapid oxidative metabolism of toxic acetaldehyde to nontoxic acetate by mitochondrial aldehyde dehydrogenase. In single reconstituted VDAC, tubulin decreases VDAC conductance, and in HepG2 hepatoma cells, free tubulin negatively modulates mitochondrial membrane potential, an effect enhanced by protein kinase A. Tubulin-dependent closure of VDAC in cancer cells contributes to suppression of mitochondrial metabolism and may underlie the Warburg phenomenon of aerobic glycolysis. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.

  14. The human red cell voltage-dependent cation channel. Part III: Distribution homogeneity and pH dependence

    DEFF Research Database (Denmark)

    Bennekou, P.; Barksmann, T. L.; Christophersen, P.

    2006-01-01

    The homogeneity of the distribution of the non-selective voltage-dependent cation channel (the NSVDC channel) in the human erythrocyte, and the pH dependence was investigated. Activation of this channel caused a uniform cellular dehydration, which was characterized by the changes in the erythrocyte...

  15. VOLTAGE-DEPENDENT SODIUM AND POTASSIUM, BUT NO CALCIUM CONDUCTANCES IN DDT1 MF-2 SMOOTH-MUSCLE CELLS

    NARCIS (Netherlands)

    MOLLEMAN, A; NELEMANS, A; VANDENAKKER, J; DUIN, M; DENHERTOG, A

    1991-01-01

    Voltage-dependent inward and outward membrane currents were investigated in the DDT1 MF-2 smooth muscle cell line using the whole-cell patch-clamp technique. Application of a pulse protocol with subsequent depolarizing voltage steps elicited an inactivating inward current and a non-inactivating outw

  16. Gated currents in isolated olfactory receptor neurons of the larval tiger salamander.

    OpenAIRE

    Firestein, S; Werblin, F S

    1987-01-01

    The electrical properties of enzymatically isolated olfactory receptor cells were studied with whole-cell patch clamp. Voltage-dependent currents could be separated into three ionic components: a transient inward sodium current, a sustained inward calcium current, and an outward potassium current. Three components of the outward current could be identified by their gating and kinetics: a calcium-dependent potassium current [IK(Ca)], a voltage-dependent potassium current [IK(V)], and a transie...

  17. Lavender oil-potent anxiolytic properties via modulating voltage dependent calcium channels.

    Science.gov (United States)

    Schuwald, Anita M; Nöldner, Michael; Wilmes, Thomas; Klugbauer, Norbert; Leuner, Kristina; Müller, Walter E

    2013-01-01

    Recent clinical data support the clinical use of oral lavender oil in patients suffering from subsyndromal anxiety. We identified the molecular mechanism of action that will alter the perception of lavender oil as a nonspecific ingredient of aromatherapy to a potent anxiolytic inhibiting voltage dependent calcium channels (VOCCs) as highly selective drug target. In contrast to previous publications where exorbitant high concentrations were used, the effects of lavender oil in behavioral, biochemical, and electrophysiological experiments were investigated in physiological concentrations in the nanomolar range, which correlate to a single dosage of 80 mg/d in humans that was used in clinical trials. We show for the first time that lavender oil bears some similarities with the established anxiolytic pregabalin. Lavender oil inhibits VOCCs in synaptosomes, primary hippocampal neurons and stably overexpressing cell lines in the same range such as pregabalin. Interestingly, Silexan does not primarily bind to P/Q type calcium channels such as pregabalin and does not interact with the binding site of pregabalin, the α2δ subunit of VOCCs. Lavender oil reduces non-selectively the calcium influx through several different types of VOCCs such as the N-type, P/Q-type and T-type VOCCs. In the hippocampus, one brain region important for anxiety disorders, we show that inhibition by lavender oil is mainly mediated via N-type and P/Q-type VOCCs. Taken together, we provide a pharmacological and molecular rationale for the clinical use of the oral application of lavender oil in patients suffering from anxiety.

  18. Lavender oil-potent anxiolytic properties via modulating voltage dependent calcium channels.

    Directory of Open Access Journals (Sweden)

    Anita M Schuwald

    Full Text Available Recent clinical data support the clinical use of oral lavender oil in patients suffering from subsyndromal anxiety. We identified the molecular mechanism of action that will alter the perception of lavender oil as a nonspecific ingredient of aromatherapy to a potent anxiolytic inhibiting voltage dependent calcium channels (VOCCs as highly selective drug target. In contrast to previous publications where exorbitant high concentrations were used, the effects of lavender oil in behavioral, biochemical, and electrophysiological experiments were investigated in physiological concentrations in the nanomolar range, which correlate to a single dosage of 80 mg/d in humans that was used in clinical trials. We show for the first time that lavender oil bears some similarities with the established anxiolytic pregabalin. Lavender oil inhibits VOCCs in synaptosomes, primary hippocampal neurons and stably overexpressing cell lines in the same range such as pregabalin. Interestingly, Silexan does not primarily bind to P/Q type calcium channels such as pregabalin and does not interact with the binding site of pregabalin, the α2δ subunit of VOCCs. Lavender oil reduces non-selectively the calcium influx through several different types of VOCCs such as the N-type, P/Q-type and T-type VOCCs. In the hippocampus, one brain region important for anxiety disorders, we show that inhibition by lavender oil is mainly mediated via N-type and P/Q-type VOCCs. Taken together, we provide a pharmacological and molecular rationale for the clinical use of the oral application of lavender oil in patients suffering from anxiety.

  19. Voltage-dependent modulation of cardiac ryanodine receptors (RyR2 by protamine.

    Directory of Open Access Journals (Sweden)

    Paula L Diaz-Sylvester

    Full Text Available It has been reported that protamine (>10 microg/ml blocks single skeletal RyR1 channels and inhibits RyR1-mediated Ca2+ release from sarcoplasmic reticulum microsomes. We extended these studies to cardiac RyR2 reconstituted into planar lipid bilayers. We found that protamine (0.02-20 microg/ml added to the cytosolic surface of fully activated RyR2 affected channel activity in a voltage-dependent manner. At membrane voltage (V(m; SR lumen-cytosol = 0 mV, protamine induced conductance transitions to several intermediate states (substates as well as full block of RyR2. At V(m>10 mV, the substate with the highest level of conductance was predominant. Increasing V(m from 0 to +80 mV, decreased the number of transitions and residence of the channel in this substate. The drop in current amplitude (full opening to substate had the same magnitude at 0 and +80 mV despite the approximately 3-fold increase in amplitude of the full opening. This is more similar to rectification of channel conductance induced by other polycations than to the action of selective conductance modifiers (ryanoids, imperatoxin. A distinctive effect of protamine (which might be shared with polylysines and histones but not with non-peptidic polycations is the activation of RyR2 in the presence of nanomolar cytosolic Ca2+ and millimolar Mg2+ levels. Our results suggest that RyRs would be subject to dual modulation (activation and block by polycationic domains of neighboring proteins via electrostatic interactions. Understanding these interactions could be important as such anomalies may be associated with the increased RyR2-mediated Ca2+ leak observed in cardiac diseases.

  20. Vestibular integrator neurons have quadratic functions due to voltage dependent conductances.

    Science.gov (United States)

    Magnani, Christophe; Eugène, Daniel; Idoux, Erwin; Moore, Lee E

    2013-12-01

    The nonlinear properties of the dendrites of the prepositus hypoglossi nucleus (PHN) neurons are essential for the operation of the vestibular neural integrator that converts a head velocity signal to one that controls eye position. A novel system of frequency probing, namely quadratic sinusoidal analysis (QSA), was used to decode the intrinsic nonlinear behavior of these neurons under voltage clamp conditions. Voltage clamp currents were measured at harmonic and interactive frequencies using specific nonoverlapping stimulation frequencies. Eigenanalysis of the QSA matrix reduces it to a remarkably compact processing unit, composed of just one or two dominant components (eigenvalues). The QSA matrix of rat PHN neurons provides signatures of the voltage dependent conductances for their particular dendritic and somatic distributions. An important part of the nonlinear response is due to the persistent sodium conductance (gNaP), which is likely to be essential for sustained effects needed for a neural integrator. It was found that responses in the range of 10 mV peak to peak could be well described by quadratic nonlinearities suggesting that effects of higher degree nonlinearities would add only marginal improvement. Therefore, the quadratic response is likely to sufficiently capture most of the nonlinear behavior of neuronal systems except for extremely large synaptic inputs. Thus, neurons have two distinct linear and quadratic functions, which shows that piecewise linear + quadratic analysis is much more complete than just piecewise linear analysis; in addition quadratic analysis can be done at a single holding potential. Furthermore, the nonlinear neuronal responses contain more frequencies over a wider frequency band than the input signal. As a consequence, they convert limited amplitude and bandwidth input signals to wider bandwidth and more complex output responses. Finally, simulations at subthreshold membrane potentials with realistic PHN neuron models

  1. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Directory of Open Access Journals (Sweden)

    Dong-Hai Liu

    Full Text Available Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  2. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Science.gov (United States)

    Liu, Dong-Hai; Huang, Xu; Guo, Xin; Meng, Xiang-Min; Wu, Yi-Song; Lu, Hong-Li; Zhang, Chun-Mei; Kim, Young-chul; Xu, Wen-Xie

    2014-01-01

    Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV) was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV) to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  3. Reduced KCNQ4-encoded voltage-dependent potassium channel activity underlies impaired ß-adrenoceptor-mediated relaxation of renal arteries in hypertension

    DEFF Research Database (Denmark)

    Chadha, Preet S; Zunke, Friederike; Zhu, Hai-Lei;

    2012-01-01

    KCNQ4-encoded voltage-dependent potassium (Kv7.4) channels are important regulators of vascular tone that are severely compromised in models of hypertension. However, there is no information as to the role of these channels in responses to endogenous vasodilators. We used a molecular knockdown...... strategy, as well as pharmacological tools, to examine the hypothesis that Kv7.4 channels contribute to ß-adrenoceptor-mediated vasodilation in the renal vasculature and underlie the vascular deficit in spontaneously hypertensive rats. Quantitative PCR and immunohistochemistry confirmed gene and protein...... spontaneously hypertensive rats, which was associated with ˜60% decrease in Kv7.4 abundance. This study provides the first evidence that Kv7 channels contribute to ß-adrenoceptor-mediated vasodilation in the renal vasculature and that abrogation of Kv7.4 channels is strongly implicated in the impaired ß...

  4. Ca2+ channel inhibitor NNC 55-0396 inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

    Science.gov (United States)

    Son, Youn Kyoung; Hong, Da Hye; Li, Hongliang; Kim, Dae-Joong; Na, Sung Hun; Park, Hongzoo; Jung, Won-Kyo; Choi, Il-Whan; Park, Won Sun

    2014-01-01

    We demonstrated the inhibitory effect of NNC 55-0396, a T-type Ca(2+) channel inhibitor, on voltage-dependent K(+) (K(V)) channels in freshly isolated rabbit coronary arterial smooth muscle cells. NNC 55-0396 decreased the amplitude of K(V) currents in a concentration-dependent manner, with an IC(50) of 0.080 μM and a Hill coefficient of 0.76.NNC 55-0396 did not affect steady-state activation and inactivation curves, indicating that the compound does not affect the voltage sensitivity of K(V) channel gating. Both the K(V) currents and the inhibitory effect of NNC 55-0396 on K(V) channels were not altered by depletion of extracellular Ca(2+) or intracellular ATP, suggesting that the inhibitory effect of NNC 55-0396 is independent of Ca(2+)-channel activity and phosphorylation-dependent signaling cascades. From these results, we concluded that NNC 55-0396 dosedependently inhibits K(V) currents, independently of Ca(2+)-channel activity and intracellular signaling cascades.

  5. Distribution of voltage-dependent and intracellular Ca2+ channels in submucosal neurons from rat distal colon.

    Science.gov (United States)

    Rehn, Matthias; Bader, Sandra; Bell, Anna; Diener, Martin

    2013-09-01

    We recently observed a bradykinin-induced increase in the cytosolic Ca2+ concentration in submucosal neurons of rat colon, an increase inhibited by blockers of voltage-dependent Ca2+ (Ca(v)) channels. As the types of Ca(v) channels used by this part of the enteric nervous system are unknown, the expression of various Ca(v) subunits has been investigated in whole-mount submucosal preparations by immunohistochemistry. Submucosal neurons, identified by a neuronal marker (microtubule-associated protein 2), are immunoreactive for Ca(v)1.2, Ca(v)1.3 and Ca(v)2.2, expression being confirmed by reverse transcription plus the polymerase chain reaction. These data agree with previous observations that the inhibition of L- and N-type Ca2+ currents strongly inhibits the response to bradykinin. However, whole-cell patch-clamp experiments have revealed that bradykinin does not enhance Ca2+ inward currents under voltage-clamp conditions. Consequently, bradykinin does not directly interact with Ca(v) channels. Instead, the kinin-induced Ca2+ influx is caused indirectly by the membrane depolarization evoked by this peptide. As intracellular Ca2+ channels on Ca(2+)-storing organelles can also contribute to Ca2+ signaling, their expression has been investigated by imaging experiments and immunohistochemistry. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) have been functionally demonstrated in submucosal neurons loaded with the Ca(2+)-sensitive fluorescent dye, fura-2. Histamine, a typical agonist coupled to the phospholipase C pathway, induces an increase in the fura-2 signal ratio, which is suppressed by 2-aminophenylborate, a blocker of IP3 receptors. The expression of IP3R1 has been confirmed by immunohistochemistry. In contrast, ryanodine, tested over a wide concentration range, evokes no increase in the cytosolic Ca2+ concentration nor is there immunohistochemical evidence for the expression of ryanodine receptors in these neurons. Thus, rat submucosal neurons are equipped

  6. Effects of arsenic trioxide on voltage-dependent potassium channels and on cell proliferation of human multiple myeloma cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jin; WANG Wei; WEI Qing-fang; FENG Tie-ming; TAN Li-jun; YANG Bao-feng

    2007-01-01

    @@ Arsenic trioxide (ATO) can induce cellular apoptosis and inhibit the activities of multiple myeloma (MM)cells in vitro,1 but how it works is not very clear. Recent studies showed that ATO worked on the voltagedependent potassium channel and L-type calcium channel in myocardial cells,2-5 but the effect of ATO on ion channels of tumor cells was rarely reported. As the potassium channel plays an important role in controlling cell proliferation,6 we studied the effects of ATO on the voltage-dependent potassium current (Ikv) of the voltage-dependent potassium channel in an MM cell line,and probed into the relationship between changes of the Ikv caused by ATO and cell proliferation.

  7. VOLTAGE STABILITY ASSESSMENT FOR WIND FARMS INTEGRATION INTO ELECTRICITY GRIDS WITH AND WITHOUT CONSIDERATION OF VOLTAGE DEPENDENT LOADS

    Directory of Open Access Journals (Sweden)

    TOMA R.

    2016-09-01

    Full Text Available The paper presents a comparative study between the effects on voltage stability of the integration of a wind farm into the electricity grid with or without voltage dependent loads in the context of different locations of a synchronous compensator from the grid. The P-V curves are built by using the PowerFactory DigSilent 15.2.2 and a DPL script that implements a simplified form of the Continuation Power Flow method.

  8. The action of a phorbol ester on voltage-dependent parameters of the sodium current in isolated hippocampal neurons.

    Science.gov (United States)

    Chizhmakov, I V; Klee, M R

    1994-03-01

    The action of a phorbol ester (phorbol-12,13-diacetate) on the voltage-activated sodium current has been investigated by the voltage-clamp method in acutely isolated pyramidal neurons from rat hippocampus. The intracellular perfusion of isolated pyramidal neurons for 30-40 min induced a gradual 10-15 mV shift in both the current-voltage relationship and voltage-dependent steady-state inactivation to more negative potentials. The application of phorbol ester (1-10 microM) to isolated neurons for the same time increased the amplitude of sodium current by 15-20%, shifted the above-mentioned voltage-dependent parameters for an additional 10-15 mV in the same direction and changed the slope of the steady-state inactivation curve. In contrast, after prolonged incubation of slices in the phorbol ester-containing solution (1-10 microM) for 0.5-3 h, subsequent application of phorbol ester at the same concentration caused neither the addition shift of the voltage-dependent characteristics of sodium channels nor the change of the slope of the steady-state inactivation curve. However, in this case an increase in the amplitude of sodium current by 15-20% during 30-40 min intracellular perfusion was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Electrolyte gate dependent high-frequency measurement of graphene field-effect transistor for sensing applications

    OpenAIRE

    Fu, W.; El Abbassi, M.; Hasler, T.; M. Jung; M. Steinacher; Calame, M.; Schönenberger,C.; Puebla-Hellmann, G.; Hellmüller, S.; T. Ihn; Wallraff, A.

    2014-01-01

    We performed radiofrequency (RF) reflectometry measurements at 2.4 GHz on electrolyte-gated graphene field-effect transistors (GFETs) utilizing a tunable stub-matching circuit for impedance matching. We demonstrate that the gate voltage dependent RF resistivity of graphene can be deduced even in the presence of the electrolyte which is in direct contact with the graphene layer. The RF resistivity is found to be consistent with its DC counterpart in the full gate voltage range. Furthermore, in...

  10. Phosphoinositide 5- and 3-phosphatase activities of a voltage-sensing phosphatase in living cells show identical voltage dependence.

    Science.gov (United States)

    Keum, Dongil; Kruse, Martin; Kim, Dong-Il; Hille, Bertil; Suh, Byung-Chang

    2016-06-28

    Voltage-sensing phosphatases (VSPs) are homologs of phosphatase and tensin homolog (PTEN), a phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] 3-phosphatase. However, VSPs have a wider range of substrates, cleaving 3-phosphate from PI(3,4)P2 and probably PI(3,4,5)P3 as well as 5-phosphate from phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and PI(3,4,5)P3 in response to membrane depolarization. Recent proposals say these reactions have differing voltage dependence. Using Förster resonance energy transfer probes specific for different PIs in living cells with zebrafish VSP, we quantitate both voltage-dependent 5- and 3-phosphatase subreactions against endogenous substrates. These activities become apparent with different voltage thresholds, voltage sensitivities, and catalytic rates. As an analytical tool, we refine a kinetic model that includes the endogenous pools of phosphoinositides, endogenous phosphatase and kinase reactions connecting them, and four exogenous voltage-dependent 5- and 3-phosphatase subreactions of VSP. We show that apparent voltage threshold differences for seeing effects of the 5- and 3-phosphatase activities in cells are not due to different intrinsic voltage dependence of these reactions. Rather, the reactions have a common voltage dependence, and apparent differences arise only because each VSP subreaction has a different absolute catalytic rate that begins to surpass the respective endogenous enzyme activities at different voltages. For zebrafish VSP, our modeling revealed that 3-phosphatase activity against PI(3,4,5)P3 is 55-fold slower than 5-phosphatase activity against PI(4,5)P2; thus, PI(4,5)P2 generated more slowly from dephosphorylating PI(3,4,5)P3 might never accumulate. When 5-phosphatase activity was counteracted by coexpression of a phosphatidylinositol 4-phosphate 5-kinase, there was accumulation of PI(4,5)P2 in parallel to PI(3,4,5)P3 dephosphorylation

  11. Cysteine mutagenesis in the voltage-dependent sodium channel structural insights and implications.

    Science.gov (United States)

    Tomaselli, G F

    1997-08-01

    The superfamily of ion channel proteins comprise multisubunit transmembrane glycoproteins that are the fundamental electrical signaling molecules in the heart and other excitable tissues. The large size and hydrophobicity of these proteins present a formidable obstacle to the generation of a crystal structure. In lieu of a high-resolution structure, complementary methods have been used to study the structure function relationships of these essential excitability proteins. Molecular cloning and biophysical analysis of heterologously expressed wild-type and mutant channel proteins have provided insights into the structural basis of the essential channel functions of permeation and gating. This powerful combination of techniques also provides dynamic structural information regarding channel proteins not likely to be forthcoming from a crystal structure. (Trends Cardiovasc Med 1997;7:211-218). © 1997, Elsevier Science Inc.

  12. Stochastic Dynamics of Electrical Membrane with Voltage-Dependent Ion Channel Fluctuations

    CERN Document Server

    Qian, Hong; Qian, Min

    2014-01-01

    Brownian ratchet like stochastic theory for the electrochemical membrane system of Hodgkin-Huxley (HH) is developed. The system is characterized by a continuous variable $Q_m(t)$, representing mobile membrane charge density, and a discrete variable $K_t$ representing ion channel conformational dynamics. A Nernst-Planck-Nyquist-Johnson type equilibrium is obtained when multiple conducting ions have a common reversal potential. Detailed balance yields a previously unknown relation between the channel switching rates and membrane capacitance, bypassing Eyring-type explicit treatment of gating charge kinetics. From a molecular structural standpoint, membrane charge $Q_m$ is a more natural dynamic variable than potential $V_m$; our formalism treats $Q_m$-dependent conformational transition rates $\\lambda_{ij}$ as intrinsic parameters. Therefore in principle, $\\lambda_{ij}$ vs. $V_m$ is experimental protocol dependent,e.g., different from voltage or charge clamping measurements. For constant membrane capacitance pe...

  13. Hysteresis in voltage-gated channels.

    Science.gov (United States)

    Villalba-Galea, Carlos A

    2016-09-30

    Ion channels constitute a superfamily of membrane proteins found in all living creatures. Their activity allows fast translocation of ions across the plasma membrane down the ion's transmembrane electrochemical gradient, resulting in a difference in electrical potential across the plasma membrane, known as the membrane potential. A group within this superfamily, namely voltage-gated channels, displays activity that is sensitive to the membrane potential. The activity of voltage-gated channels is controlled by the membrane potential, while the membrane potential is changed by these channels' activity. This interplay produces variations in the membrane potential that have evolved into electrical signals in many organisms. These signals are essential for numerous biological processes, including neuronal activity, insulin release, muscle contraction, fertilization and many others. In recent years, the activity of the voltage-gated channels has been observed not to follow a simple relationship with the membrane potential. Instead, it has been shown that the activity of voltage-gated channel displays hysteresis. In fact, a growing number of evidence have demonstrated that the voltage dependence of channel activity is dynamically modulated by activity itself. In spite of the great impact that this property can have on electrical signaling, hysteresis in voltage-gated channels is often overlooked. Addressing this issue, this review provides examples of voltage-gated ion channels displaying hysteretic behavior. Further, this review will discuss how Dynamic Voltage Dependence in voltage-gated channels can have a physiological role in electrical signaling. Furthermore, this review will elaborate on the current thoughts on the mechanism underlying hysteresis in voltage-gated channels.

  14. A conserved threonine in the S1-S2 loop of KV7.2 and K V7.3 channels regulates voltage-dependent activation.

    Science.gov (United States)

    Füll, Yvonne; Seebohm, Guiscard; Lerche, Holger; Maljevic, Snezana

    2013-06-01

    The voltage-gated potassium channels KV7.2 and KV7.3 (KCNQ2/3 genes) play an important role in regulating neuronal excitability. More than 50 KCNQ2/3 mutations have been identified to cause an inherited form of epilepsy in newborns. For two of those (E119G and S122L) found in the S1-S2 region of KV7.2, we previously showed a decreased channel availability mainly at action potential subthreshold voltages caused by a slight depolarizing shift of the activation curve. Interestingly, recent studies revealed that a threonine residue within the S1-S2 loop, highly conserved among different classes of KV channels, is crucial for both their function and surface expression. To investigate the functional role of the homologous threonine residues in KV7.2 (T114) and KV7.3 (T144) channels, we replaced them with alanine and examined the electrophysiological properties using heterologous expression in CHO cells and whole cell patch clamping. Channels comprising mutant subunits yielded decreased potassium currents with slowed activation and accelerated deactivation kinetics. However, the most striking effect was a depolarizing shift in the voltage dependence of activation reaching +30 mV upon co-expression of both mutant subunits. Potential interactions of T114 within the channel were analyzed by creating a 3D homology model of KV7.2 in an open state suggesting that this residue plays a central role in the formation of a stable interface between the S1-S2 and the S5 segment helices. This could be the explanation why substitution of the conserved threonine in KV7.2 and KV7.3 channels destabilizes the open and favors the closed state of these channels.

  15. The N-Terminal Peptides of the Three Human Isoforms of the Mitochondrial Voltage-Dependent Anion Channel Have Different Helical Propensities.

    Science.gov (United States)

    Guardiani, Carlo; Scorciapino, Mariano Andrea; Amodeo, Giuseppe Federico; Grdadolnik, Joze; Pappalardo, Giuseppe; De Pinto, Vito; Ceccarelli, Matteo; Casu, Mariano

    2015-09-15

    The voltage-dependent anion channel (VDAC) is the main mitochondrial porin allowing the exchange of ions and metabolites between the cytosol and the mitochondrion. In addition, VDAC was found to actively interact with proteins playing a fundamental role in the regulation of apoptosis and being of central interest in cancer research. VDAC is a large transmembrane β-barrel channel, whose N-terminal helical fragment adheres to the channel interior, partially closing the pore. This fragment is considered to play a key role in protein stability and function as well as in the interaction with apoptosis-related proteins. Three VDAC isoforms are differently expressed in higher eukaryotes, for which distinct and complementary roles are proposed. In this work, the folding propensity of their N-terminal fragments has been compared. By using multiple spectroscopic techniques, and complementing the experimental results with theoretical computer-assisted approaches, we have characterized their conformational equilibrium. Significant differences were found in the intrinsic helical propensity of the three peptides, decreasing in the following order: hVDAC2 > hVDAC3 > hVDAC1. In light of the models proposed in the literature to explain voltage gating, selectivity, and permeability, as well as interactions with functionally related proteins, our results suggest that the different chemicophysical properties of the N-terminal domain are possibly correlated to different functions for the three isoforms. The overall emerging picture is that a similar transmembrane water accessible conduit has been equipped with not identical domains, whose differences can modulate the functional roles of the three VDAC isoforms.

  16. Effect of angiotensin II-induced arterial hypertension on the voltage-dependent contractions of mouse arteries.

    Science.gov (United States)

    Fransen, Paul; Van Hove, Cor E; Leloup, Arthur J A; Schrijvers, Dorien M; De Meyer, Guido R Y; De Keulenaer, Gilles W

    2016-02-01

    Arterial hypertension (AHT) affects the voltage dependency of L-type Ca(2+) channels in cardiomyocytes. We analyzed the effect of angiotensin II (AngII)-induced AHT on L-type Ca(2+) channel-mediated isometric contractions in conduit arteries. AHT was induced in C57Bl6 mice with AngII-filled osmotic mini-pumps (4 weeks). Normotensive mice treated with saline-filled osmotic mini-pumps were used for comparison. Voltage-dependent contractions mediated by L-type Ca(2+) channels were studied in vaso-reactive studies in vitro in isolated aortic and femoral arteries by using extracellular K(+) concentration-response (KDR) experiments. In aortic segments, AngII-induced AHT significantly sensitized isometric contractions induced by elevated extracellular K(+) and depolarization. This sensitization was partly prevented by normalizing blood pressure with hydralazine, suggesting that it was caused by AHT rather than by direct AngII effects on aortic smooth muscle cells. The EC50 for extracellular K(+) obtained in vitro correlated significantly with the rise in arterial blood pressure induced by AngII in vivo. The AHT-induced sensitization persisted when aortic segments were exposed to levcromakalim or to inhibitors of basal nitric oxide release. Consistent with these observations, AngII-treatment also sensitized the vaso-relaxing effects of the L-type Ca(2+) channel blocker diltiazem during K(+)-induced contractions. Unlike aorta, AngII-treatment desensitized the isometric contractions to depolarization in femoral arteries pointing to vascular bed specific responses of arteries to hypertension. AHT affects the voltage-dependent L-type Ca(2+) channel-mediated contraction of conduit arteries. This effect may contribute to the decreased vascular compliance in AHT and explain the efficacy of Ca(2+) channel blockers to reduce vascular stiffness and central blood pressure in AHT.

  17. Analysis and Comparison of Voltage Dependent Charging Strategies for Single-Phase Electric Vehicles in an Unbalanced Danish Distribution Grid

    DEFF Research Database (Denmark)

    Álvarez, Jorge Nájera; Knezovic, Katarina; Marinelli, Mattia

    2016-01-01

    This paper studies four voltage dependent solutions for modulating the charging of multiple Electric Vehicles (EVs) in a real Danish network. Uncontrolled EV charging, especially in grid with high EV penetration, can result in overloaded lines and transformers, low-voltages and other performance......-in on phases with lower voltages are constrained during the charging period. In order to solve instability issues which may occur due to lack of communication between the controllers, several improvements are applied to the aforementioned droop control. Simulation results demonstrate the performance...

  18. Neuroprotective activity of stiripentol with a possible involvement of voltage-dependent calcium and sodium channels.

    Science.gov (United States)

    Verleye, Marc; Buttigieg, Dorothée; Steinschneider, Rémy

    2016-02-01

    A growing body of data has shown that recurrent epileptic seizures may be caused by an excessive release of the excitatory neurotransmitter glutamate in the brain. Glutamatergic overstimulation results in massive neuronal influxes of calcium and sodium through N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainic acid glutamate subtype receptors and also through voltage-gated calcium and sodium channels. These persistent and abnormal sodium and calcium entry points have deleterious consequences (neurotoxicity) for neuronal function. The therapeutic value of an antiepileptic drug would include not only control of seizure activity but also protection of neuronal tissue. The present study examines the in vitro neuroprotective effects of stiripentol, an antiepileptic compound with γ-aminobutyric acidergic properties, on neuronal-astroglial cultures from rat cerebral cortex exposed to oxygen-glucose deprivation (OGD) or to glutamate (40 µM for 20 min), two in vitro models of brain injury. In addition, the affinity of stiripentol for the different glutamate receptor subtypes and the interaction with the cell influx of Na(+) and of Ca(2+) enhanced by veratridine and NMDA, respectively, are assessed. Stiripentol (10-100 µM) included in the culture medium during OGD or with glutamate significantly increased the number of surviving neurons relative to controls. Stiripentol displayed no binding affinity for different subtypes of glutamate receptors (IC50  >100 µM) but significantly blocked the entry of Na(+) and Ca(2+) activated by veratridine and NMDA, respectively. These results suggest that Na(+) and Ca(2+) channels could contribute to the neuroprotective properties of sitiripentol.

  19. Voltage-gated lipid ion channels

    DEFF Research Database (Denmark)

    Blicher, Andreas; Heimburg, Thomas Rainer

    2013-01-01

    Synthetic lipid membranes can display channel-like ion conduction events even in the absence of proteins. We show here that these events are voltage-gated with a quadratic voltage dependence as expected from electrostatic theory of capacitors. To this end, we recorded channel traces and current...... histograms in patch-experiments on lipid membranes. We derived a theoretical current-voltage relationship for pores in lipid membranes that describes the experimental data very well when assuming an asymmetric membrane. We determined the equilibrium constant between closed and open state and the open...... probability as a function of voltage. The voltage-dependence of the lipid pores is found comparable to that of protein channels. Lifetime distributions of open and closed events indicate that the channel open distribution does not follow exponential statistics but rather power law behavior for long open times...

  20. Molecular characterization and functional expression of the Apis mellifera voltage-dependent Ca2+ channels.

    Science.gov (United States)

    Cens, Thierry; Rousset, Matthieu; Collet, Claude; Charreton, Mercedes; Garnery, Lionel; Le Conte, Yves; Chahine, Mohamed; Sandoz, Jean-Christophe; Charnet, Pierre

    2015-03-01

    Voltage-gated Ca(2+) channels allow the influx of Ca(2+) ions from the extracellular space upon membrane depolarization and thus serve as a transducer between membrane potential and cellular events initiated by Ca(2+) transients. Most insects are predicted to possess three genes encoding Cavα, the main subunit of Ca(2+) channels, and several genes encoding the two auxiliary subunits, Cavβ and Cavα2δ; however very few of these genes have been cloned so far. Here, we cloned three full-length cDNAs encoding the three Cavα subunits (AmelCav1a, AmelCav2a and AmelCav3a), a cDNA encoding a novel variant of the Cavβ subunit (AmelCavβc), and three full-length cDNAs encoding three Cavα2δ subunits (AmelCavα2δ1 to 3) of the honeybee Apis mellifera. We identified several alternative or mutually exclusive exons in the sequence of the AmelCav2 and AmelCav3 genes. Moreover, we detected a stretch of glutamine residues in the C-terminus of the AmelCav1 subunit that is reminiscent of the motif found in the human Cav2.1 subunit of patients with Spinocerebellar Ataxia type 6. All these subunits contain structural domains that have been identified as functionally important in their mammalian homologues. For the first time, we could express three insect Cavα subunits in Xenopus oocytes and we show that AmelCav1a, 2a and 3a form Ca(2+) channels with distinctive properties. Notably, the co-expression of AmelCav1a or AmelCav2a with AmelCavβc and AmCavα2δ1 produces High Voltage-Activated Ca(2+) channels. On the other hand, expression of AmelCav3a alone leads to Low Voltage-Activated Ca(2+) channels.

  1. Development of a voltage-dependent current noise algorithm for conductance-based stochastic modelling of auditory nerve fibres.

    Science.gov (United States)

    Badenhorst, Werner; Hanekom, Tania; Hanekom, Johan J

    2016-12-01

    This study presents the development of an alternative noise current term and novel voltage-dependent current noise algorithm for conductance-based stochastic auditory nerve fibre (ANF) models. ANFs are known to have significant variance in threshold stimulus which affects temporal characteristics such as latency. This variance is primarily caused by the stochastic behaviour or microscopic fluctuations of the node of Ranvier's voltage-dependent sodium channels of which the intensity is a function of membrane voltage. Though easy to implement and low in computational cost, existing current noise models have two deficiencies: it is independent of membrane voltage, and it is unable to inherently determine the noise intensity required to produce in vivo measured discharge probability functions. The proposed algorithm overcomes these deficiencies while maintaining its low computational cost and ease of implementation compared to other conductance and Markovian-based stochastic models. The algorithm is applied to a Hodgkin-Huxley-based compartmental cat ANF model and validated via comparison of the threshold probability and latency distributions to measured cat ANF data. Simulation results show the algorithm's adherence to in vivo stochastic fibre characteristics such as an exponential relationship between the membrane noise and transmembrane voltage, a negative linear relationship between the log of the relative spread of the discharge probability and the log of the fibre diameter and a decrease in latency with an increase in stimulus intensity.

  2. Blockade of the voltage-dependent sodium current in isolated rat hippocampal neurons by tetrodotoxin and lidocaine.

    Science.gov (United States)

    Kaneda, M; Oyama, Y; Ikemoto, Y; Akaike, N

    1989-04-10

    The effects of tetrodotoxin and lidocaine on the voltage-dependent sodium current (INa) were studied in the CA1 pyramidal neurons isolated acutely from rat hippocampus using a 'concentration-clamp' technique which combines the intracellular perfusion with a rapid external solution change within a few ms. Tetrodotoxin (TTX) exerted its inhibitory action in time- and dose-dependent manner on the peak amplitude of INa without any apparent effects on both the current activation and inactivation processes of the current. The time course for reaching a steady-state of the inhibitory action shortened with increasing TTX concentration, but the time course of recovery from the inhibition after washing out the toxin was quite the same at any concentrations used. Lidocaine also inhibited dose-dependently the INa, though with slightly accelerating both the activation and inactivation processes. The time courses for reaching the steady-state inhibition and the recovery from the inhibition were much shorter than those in the case of TTX. The results indicate that the voltage-dependent sodium channel of mammalian brain neuron is TTX-sensitive as well as that of peripheral neuron and that the mode of TTX inhibition on the INa is quite different from that of lidocaine.

  3. Atomic-Scale Spectroscopy of Gated Monolayer MoS2.

    Science.gov (United States)

    Zhou, Xiaodong; Kang, Kibum; Xie, Saien; Dadgar, Ali; Monahan, Nicholas R; Zhu, X-Y; Park, Jiwoong; Pasupathy, Abhay N

    2016-05-11

    The electronic properties of semiconducting monolayer transition-metal dichalcogenides can be tuned by electrostatic gate potentials. Here we report gate-tunable imaging and spectroscopy of monolayer MoS2 by atomic-resolution scanning tunneling microscopy/spectroscopy (STM/STS). Our measurements are performed on large-area samples grown by metal-organic chemical vapor deposition (MOCVD) techniques on a silicon oxide substrate. Topographic measurements of defect density indicate a sample quality comparable to single-crystal MoS2. From gate voltage dependent spectroscopic measurements, we determine that in-gap states exist in or near the MoS2 film at a density of 1.3 × 10(12) eV(-1) cm(-2). By combining the single-particle band gap measured by STS with optical measurements, we estimate an exciton binding energy of 230 meV on this substrate, in qualitative agreement with numerical simulation. Grain boundaries are observed in these polycrystalline samples, which are seen to not have strong electronic signatures in STM imaging.

  4. Voltage-Gated Proton Channels: Molecular Biology, Physiology, and Pathophysiology of the HV Family

    Science.gov (United States)

    2013-01-01

    Voltage-gated proton channels (HV) are unique, in part because the ion they conduct is unique. HV channels are perfectly selective for protons and have a very small unitary conductance, both arguably manifestations of the extremely low H+ concentration in physiological solutions. They open with membrane depolarization, but their voltage dependence is strongly regulated by the pH gradient across the membrane (ΔpH), with the result that in most species they normally conduct only outward current. The HV channel protein is strikingly similar to the voltage-sensing domain (VSD, the first four membrane-spanning segments) of voltage-gated K+ and Na+ channels. In higher species, HV channels exist as dimers in which each protomer has its own conduction pathway, yet gating is cooperative. HV channels are phylogenetically diverse, distributed from humans to unicellular marine life, and perhaps even plants. Correspondingly, HV functions vary widely as well, from promoting calcification in coccolithophores and triggering bioluminescent flashes in dinoflagellates to facilitating killing bacteria, airway pH regulation, basophil histamine release, sperm maturation, and B lymphocyte responses in humans. Recent evidence that hHV1 may exacerbate breast cancer metastasis and cerebral damage from ischemic stroke highlights the rapidly expanding recognition of the clinical importance of hHV1. PMID:23589829

  5. Voltage-dependent K channels in protoplasts of trap-lobe cells of Dionaea muscipula.

    Science.gov (United States)

    Iijima, T; Hagiwara, S

    1987-01-01

    The outward rectification of the K+ current in mesophyll cell protoplasts from trap-lobes of Dionaea muscipula was studied with the patch-clamp technique. The rectification had instantaneous and time-dependent components. Changes in [K+]i strongly affected the conductance voltage relation of the plasma membrane while changes in [K+]o had little effect on the relation. Thus, the outward rectification depends on the membrane voltage and the concentration of intracellular K+. Corresponding single-channel activities were observed both in the intact membrane (cell-attached recording) and in excised patches. The single-channel conductance was about 3.3 pS with symmetrical solutions containing 30 mM K+.

  6. [Role of calcineurin in down-regulation of left ventricular transmural voltage- dependent K(+) currents in mice with heart failure].

    Science.gov (United States)

    Shi, Chen-Xia; Dong, Fang; Chang, Yan-Chao; Wang, Xiao-Feng; Xu, Yan-Fang

    2015-08-25

    The aim of the present study was to investigate the role of calcineurin in the down-regulation of left ventricular transmural voltage-dependent K(+) currents in heart failure. Transverse aorta was banded by using microsurgical techniques to create mouse heart failure model. Sham-operated (Sham) or aorta banded (Band) mice were randomized to receive calcineurin inhibitor cyclosporine A (CsA) or vehicle. The densities and kinetic properties of voltage-dependent K(+) currents, as well as action potential (AP), of left ventricular subendocardial (Endo) and subepicardial (Epi) myocytes were determined by using whole-cell patch-clamp technique. The results showed that calcineurin activity was significant higher in Endo myocytes than that in Epi ones in all the groups. Compared with Sham group, Band mice showed significantly increased calcineurin activity both in Endo and Epi myocytes. CsA significantly reduced calcineurin activity in Band mice. CsA treatment in Band mice partially reversed the down-regulation of Ito density, completely reversed the down-regulation of IK,slow density both in Endo and Epi myocytes, and Iss density in Endo myocytes. In addition, CsA treatment in Band mice partially antagonized the prolongation of action potential duration (APD), and APD at 50% (APD50) and 90% repolarization (APD90) were significantly reduced. Because of non-parallel shortening of APD in Endo and Epi myocytes, the ratio of Endo/Epi APD90 was reduced from 4.8:1 in Band mice to 2.6:1 in CsA-treated mice, which was close to that in Sham mice. The results suggest that non-parallel activation of calcineurin in Endo and Epi myocytes contributes to the down-regulation of transmural voltage-dependent K(+) currents and the amplification of transmural dispersion of repolarization (TDR) in left ventricular failure hearts. Inhibition of calcineurin may be a potential new therapeutic strategy to prevent and cure arrhythmias and sudden death in heart failure.

  7. Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D;

    2001-01-01

    .2 protein was demonstrated by immunochemical labeling of rat preglomerular vasculature and juxtamedullary efferent arterioles and vasa recta. Cortical efferent arterioles were not immunopositive. Recordings of intracellular calcium concentration with digital fluorescence imaging microscopy showed......The distribution of voltage-dependent calcium channels in kidney pre- and postglomerular resistance vessels was determined at the molecular and functional levels. Reverse transcription-polymerase chain reaction analysis of microdissected rat preglomerular vessels and cultured smooth muscle cells...... showed coexpression of mRNAs for T-type subunits (Ca(V)3.1, Ca(V)3.2) and for an L-type subunit (Ca(V)1.2). The same expression pattern was observed in juxtamedullary efferent arterioles and outer medullary vasa recta. No calcium channel messages were detected in cortical efferent arterioles. Ca(V)1...

  8. Characterization and functional analysis of voltage-dependent anion channel 1 (VDAC1) from orange-spotted grouper (Epinephelus coioides).

    Science.gov (United States)

    Shi, Yan; Zhao, Zhe; Hong, Xiaoyou; Chen, Kunci; Zhu, Xinping

    2014-07-01

    The voltage-dependent anion channel (VDAC) is a highly conserved integral protein of mitochondria in different eukaryotic species. It forms a selective channel in the mitochondrial outer membrane that serves as the controlled pathway for small metabolites and ions. In this study, a VDAC gene, EcVDAC1, was isolated from orange-spotted grouper (Epinephelus coioides). The EcVDAC1 exhibits ubiquitous expression in various tissues of orange-spotted grouper and is upregulated in liver, gill, and spleen after stimulation with lipopolysaccharides (LPS). Subcellular localization analysis shows that the EcVDAC1 protein colocalized with the mitochondria. A caspase-3 assay demonstrates that overexpression of the EcVDAC1 induced apoptotic cell death in fathead minnow cells. The data presented in this study provide new information regarding the relationship between LPS and the EcVDAC1 gene, suggesting that the fish VDAC1 gene may play an important role in antibacterial immune response.

  9. Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

    Indian Academy of Sciences (India)

    HAN SOL KIM; HONGLIANG LI; HYE WON KIM; SUNG EUN SHIN; IL-WHAN CHOI; AMY L FIRTH; HYOWEON BANG; YOUNG MIN BAE; WON SUN PARK

    2016-12-01

    We examined the effects of the selective serotonin reuptake inhibitor (SSRI) sertraline on voltage-dependent K+ (Kv)channels in freshly isolated rabbit coronary arterial smooth muscle cells using the voltage-clamp technique. Sertralinedecreased the Kv channel current in a dose-dependent manner, with an IC50 value of 0.18 μM and a slope value (Hillcoefficient) of 0.61. Although the application of 1 μM sertraline did not affect the steady-state activation curves,sertraline caused a significant, negative shift in the inactivation curves. Pretreatment with another SSRI, paroxetine,had no significant effect on Kv currents and did not alter the inhibitory effects of sertraline on Kv currents. From theseresults, we concluded that sertraline dose-dependently inhibited Kv currents independently of serotonin reuptakeinhibition by shifting inactivation curves to a more negative potential.

  10. Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

    Science.gov (United States)

    Kim, Han Sol; Li, Hongliang; Kim, Hye Won; Shin, Sung Eun; Choi, Il-Whan; Firth, Amy L; Bang, Hyoweon; Bae, Young Min; Park, Won Sun

    2016-12-01

    We examined the effects of the selective serotonin reuptake inhibitor (SSRI) sertraline on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using the voltage-clamp technique. Sertraline decreased the Kv channel current in a dose-dependent manner, with an IC50 value of 0.18 mu M and a slope value (Hill coefficient) of 0.61. Although the application of 1 mu M sertraline did not affect the steady-state activation curves, sertraline caused a significant, negative shift in the inactivation curves. Pretreatment with another SSRI, paroxetine, had no significant effect on Kv currents and did not alter the inhibitory effects of sertraline on Kv currents. From these results, we concluded that sertraline dose-dependently inhibited Kv currents independently of serotonin reuptake inhibition by shifting inactivation curves to a more negative potential.

  11. Temperature and bias voltage dependence of Co/Pd multilayer-based magnetic tunnel junctions with perpendicular magnetic anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Kugler, Zoe, E-mail: zkugler@physik.uni-bielefeld.d [Bielefeld University, Department of Physics, Universitaetsstr. 25, 33615 Bielefeld (Germany); Drewello, Volker; Schaefers, Markus; Schmalhorst, Jan; Reiss, Guenter; Thomas, Andy [Bielefeld University, Department of Physics, Universitaetsstr. 25, 33615 Bielefeld (Germany)

    2011-01-15

    Temperature- and bias voltage-dependent transport measurements of magnetic tunnel junctions (MTJs) with perpendicularly magnetized Co/Pd electrodes are presented. Magnetization measurements of the Co/Pd multilayers are performed to characterize the electrodes. The effects of the Co layer thickness in the Co/Pd bilayers, the annealing temperature, the Co thickness at the MgO barrier interface, and the number of bilayers on the tunneling magneto resistance (TMR) effect are investigated. TMR-ratios of about 11% at room temperature and 18.5% at 13 K are measured and two well-defined switching fields are observed. The results are compared to measurements of MTJs with Co-Fe-B electrodes and in-plane anisotropy.

  12. Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D

    2001-01-01

    The distribution of voltage-dependent calcium channels in kidney pre- and postglomerular resistance vessels was determined at the molecular and functional levels. Reverse transcription-polymerase chain reaction analysis of microdissected rat preglomerular vessels and cultured smooth muscle cells...... showed coexpression of mRNAs for T-type subunits (Ca(V)3.1, Ca(V)3.2) and for an L-type subunit (Ca(V)1.2). The same expression pattern was observed in juxtamedullary efferent arterioles and outer medullary vasa recta. No calcium channel messages were detected in cortical efferent arterioles. Ca(V)1.......2 protein was demonstrated by immunochemical labeling of rat preglomerular vasculature and juxtamedullary efferent arterioles and vasa recta. Cortical efferent arterioles were not immunopositive. Recordings of intracellular calcium concentration with digital fluorescence imaging microscopy showed...

  13. Flufenamic acid decreases neuronal excitability through modulation of voltage-gated sodium channel gating.

    Science.gov (United States)

    Yau, Hau-Jie; Baranauskas, Gytis; Martina, Marco

    2010-10-15

    The electrophysiological phenotype of individual neurons critically depends on the biophysical properties of the voltage-gated channels they express. Differences in sodium channel gating are instrumental in determining the different firing phenotypes of pyramidal cells and interneurons; moreover, sodium channel modulation represents an important mechanism of action for many widely used CNS drugs. Flufenamic acid (FFA) is a non-steroidal anti-inflammatory drug that has been long used as a blocker of calcium-dependent cationic conductances. Here we show that FFA inhibits voltage-gated sodium currents in hippocampal pyramidal neurons; this effect is dose-dependent with IC(50) = 189 μm. We used whole-cell and nucleated patch recordings to investigate the mechanisms of FFA modulation of TTX-sensitive voltage-gated sodium current. Our data show that flufenamic acid slows down the inactivation process of the sodium current, while shifting the inactivation curve ~10 mV toward more hyperpolarized potentials. The recovery from inactivation is also affected in a voltage-dependent way, resulting in slower recovery at hyperpolarized potentials. Recordings from acute slices demonstrate that FFA reduces repetitive- and abolishes burst-firing in CA1 pyramidal neurons. A computational model based on our data was employed to better understand the mechanisms of FFA action. Simulation data support the idea that FFA acts via a novel mechanism by reducing the voltage dependence of the sodium channel fast inactivation rates. These effects of FFA suggest that it may be an effective anti-epileptic drug.

  14. Voltage dependence of Hodgkin-Huxley rate functions for a multistage K+ channel voltage sensor within a membrane

    Science.gov (United States)

    Vaccaro, S. R.

    2014-11-01

    The activation of a K+channel sensor in two sequential stages during a voltage clamp may be described as the translocation of a Brownian particle in an energy landscape with two large barriers between states. A solution of the Smoluchowski equation for a square-well approximation to the potential function of the S4 voltage sensor satisfies a master equation and has two frequencies that may be determined from the forward and backward rate functions. When the higher-frequency terms have small amplitude, the solution reduces to the relaxation of a rate equation, where the derived two-state rate functions are dependent on the relative magnitude of the forward rates (α and γ ) and the backward rates (β and δ ) for each stage. In particular, the voltage dependence of the Hodgkin-Huxley rate functions for a K+channel may be derived by assuming that the rate functions of the first stage are large relative to those of the second stage—α ≫γ and β ≫δ . For a Shaker IR K+ channel, the first forward and backward transitions are rate limiting (α <γ and δ ≪β ), and for an activation process with either two or three stages, the derived two-state rate functions also have a voltage dependence that is of a similar form to that determined for the squid axon. The potential variation generated by the interaction between a two-stage K+ ion channel and a noninactivating Na+ ion channel is determined by the master equation for K+channel activation and the ionic current equation when the Na+channel activation time is small, and if β ≪δ and α ≪γ , the system may exhibit a small amplitude oscillation between spikes, or mixed-mode oscillation, in which the slow closed state modulates the K+ ion channel conductance in the membrane.

  15. Functional coupling between sodium-activated potassium channels and voltage-dependent persistent sodium currents in cricket Kenyon cells.

    Science.gov (United States)

    Takahashi, Izumi; Yoshino, Masami

    2015-10-01

    In this study, we examined the functional coupling between Na(+)-activated potassium (KNa) channels and Na(+) influx through voltage-dependent Na(+) channels in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Single-channel activity of KNa channels was recorded with the cell-attached patch configuration. The open probability (Po) of KNa channels increased with increasing Na(+) concentration in a bath solution, whereas it decreased by the substitution of Na(+) with an equimolar concentration of Li(+). The Po of KNa channels was also found to be reduced by bath application of a high concentration of TTX (1 μM) and riluzole (100 μM), which inhibits both fast (INaf) and persistent (INaP) Na(+) currents, whereas it was unaffected by a low concentration of TTX (10 nM), which selectively blocks INaf. Bath application of Cd(2+) at a low concentration (50 μM), as an inhibitor of INaP, also decreased the Po of KNa channels. Conversely, bath application of the inorganic Ca(2+)-channel blockers Co(2+) and Ni(2+) at high concentrations (500 μM) had little effect on the Po of KNa channels, although Cd(2+) (500 μM) reduced the Po of KNa channels. Perforated whole cell clamp analysis further indicated the presence of sustained outward currents for which amplitude was dependent on the amount of Na(+) influx. Taken together, these results indicate that KNa channels could be activated by Na(+) influx passing through voltage-dependent persistent Na(+) channels. The functional significance of this coupling mechanism was discussed in relation to the membrane excitability of Kenyon cells and its possible role in the formation of long-term memory.

  16. trans-Caryophyllene, a Natural Sesquiterpene, Causes Tracheal Smooth Muscle Relaxation through Blockade of Voltage-Dependent Ca2+ Channels

    Directory of Open Access Journals (Sweden)

    Jader Santos Cruz

    2012-10-01

    Full Text Available trans-Caryophyllene is a major component in the essential oils of various species of medicinal plants used in popular medicine in Brazil. It belongs to the chemical class of the sesquiterpenes and has been the subject of a number of studies. Here, we evaluated the effects of this compound in airway smooth muscle. The biological activities of trans-caryophyllene were examined in isolated bath organs to investigate the effect in basal tonus. Electromechanical and pharmacomechanical couplings were evaluated through the responses to K+ depolarization and exposure to acetylcholine (ACh, respectively. Isolated cells of rat tracheal smooth muscle were used to investigate trans-caryophyllene effects on voltage-dependent Ca2+ channels by using the whole-cell voltage-clamp configuration of the patch-clamp technique. trans-Caryophyllene showed more efficiency in the blockade of electromechanical excitation-contraction coupling while it has only minor inhibitory effect on pharmacomechanical coupling. Epithelium removal does not modify tracheal smooth muscle response elicited by trans-caryophyllene in the pharmacomechanical coupling. Under Ca2+-free conditions, pre-exposure to trans-caryophyllene did not reduce the contraction induced by ACh in isolated rat tracheal smooth muscle, regardless of the presence of intact epithelium. In the whole-cell configuration, trans-caryophyllene (3 mM, inhibited the inward Ba2+ current (IBa to approximately 50% of control levels. Altogether, our results demonstrate that trans-caryophyllene has anti-spasmodic activity on rat tracheal smooth muscle which could be explained, at least in part, by the voltage-dependent Ca2+ channels blockade.

  17. Decreases of voltage-dependent K+ currents densities in ventricular myocytes of guinea pigs by chronic oxidant stress

    Institute of Scientific and Technical Information of China (English)

    De-li DONG; Yan LIU; Yu-hong ZHOU; Wei-hua SONG; He WANG; Bao-feng YANG

    2004-01-01

    AIM: To determine the changes of delayed rectifier K+ currents (Ik) and inward rectifier K+ currents (Ik1) in the ventricular myocytes of guinea pigs during the gradual apoptotic process by the chronic oxidant stress treatment.METHODS: H2O250 μmol/L (24 h) was used for inducing apoptosis in the cardiomyocytes culture of neonatal rats and to treat the isolated ventricular myocytes of adult guinea pigs in vitro for 24 h. Apoptosis was evaluated by TUNEL methods and voltage-dependent K+ currents were recorded by patch-clamp techniques. RESULTS: H2O250 μmol/L (24 h) induced cell apoptosis in the cardiomyocytes culture of neonatal rats. This concentration was used to treat the isolated ventricular myocytes of adult guinea pigs in vitro for 24 h and the voltage-dependent K+currents densities (Ik, Ik1) were down-regulated. The densities of the delayed rectifier K+ currents (Ik) in 50 μmol/L H2O2 group were 2.52±0.57 pA/pF vs 5.73±1.84 pA/pF in the control group at +50 mV (n=8, P<0.01). The densities of the inward rectifier K+ currents (Ik1) in 50 μmol/L H2O2 group were -13.9±2.70 pA/pF, 2.52±0.57 pA/pF vs -59.7± 11.9 pA/pF, 5.73± 1.84 pA/pF in the control group at -120 mV (n=8, P<0.01) and -40 mV (n=8, P<0.05), respectively. The extent of inward rectifier property of Ik1 was weakened by 50μmol/L H2O2 treatment. CONCLUSION: The densities of Ik, Ik1 in the cardiomyocytes of guinea pigs were downregulated and the inward rectifier property of Ik1 was weakened during the gradual apoptotic process after 50 μmol/L H2O2 treatment for 24 h.

  18. Characterization of the Ca2+-gated and voltage-dependent K+-channel Slo-1 of nematodes and its interaction with emodepside.

    Science.gov (United States)

    Kulke, Daniel; von Samson-Himmelstjerna, Georg; Miltsch, Sandra M; Wolstenholme, Adrian J; Jex, Aaron R; Gasser, Robin B; Ballesteros, Cristina; Geary, Timothy G; Keiser, Jennifer; Townson, Simon; Harder, Achim; Krücken, Jürgen

    2014-12-01

    The cyclooctadepsipeptide emodepside and its parent compound PF1022A are broad-spectrum nematicidal drugs which are able to eliminate nematodes resistant to other anthelmintics. The mode of action of cyclooctadepsipeptides is only partially understood, but involves the latrophilin Lat-1 receptor and the voltage- and calcium-activated potassium channel Slo-1. Genetic evidence suggests that emodepside exerts its anthelmintic activity predominantly through Slo-1. Indeed, slo-1 deficient Caenorhabditis elegans strains are completely emodepside resistant. However, direct effects of emodepside on Slo-1 have not been reported and these channels have only been characterized for C. elegans and related Strongylida. Molecular and bioinformatic analyses identified full-length Slo-1 cDNAs of Ascaris suum, Parascaris equorum, Toxocara canis, Dirofilaria immitis, Brugia malayi, Onchocerca gutturosa and Strongyloides ratti. Two paralogs were identified in the trichocephalids Trichuris muris, Trichuris suis and Trichinella spiralis. Several splice variants encoding truncated channels were identified in Trichuris spp. Slo-1 channels of trichocephalids form a monophyletic group, showing that duplication occurred after the divergence of Enoplea and Chromadorea. To explore the function of a representative protein, C. elegans Slo-1a was expressed in Xenopus laevis oocytes and studied in electrophysiological (voltage-clamp) experiments. Incubation of oocytes with 1-10 µM emodepside caused significantly increased currents over a wide range of step potentials in the absence of experimentally increased intracellular Ca2+, suggesting that emodepside directly opens C. elegans Slo-1a. Emodepside wash-out did not reverse the effect and the Slo-1 inhibitor verruculogen was only effective when applied before, but not after, emodepside. The identification of several splice variants and paralogs in some parasitic nematodes suggests that there are substantial differences in channel properties among species. Most importantly, this study showed for the first time that emodepside directly opens a Slo-1 channel, significantly improving the understanding of the mode of action of this drug class.

  19. Characterization of the Ca2+-gated and voltage-dependent K+-channel Slo-1 of nematodes and its interaction with emodepside.

    Directory of Open Access Journals (Sweden)

    Daniel Kulke

    2014-12-01

    Full Text Available The cyclooctadepsipeptide emodepside and its parent compound PF1022A are broad-spectrum nematicidal drugs which are able to eliminate nematodes resistant to other anthelmintics. The mode of action of cyclooctadepsipeptides is only partially understood, but involves the latrophilin Lat-1 receptor and the voltage- and calcium-activated potassium channel Slo-1. Genetic evidence suggests that emodepside exerts its anthelmintic activity predominantly through Slo-1. Indeed, slo-1 deficient Caenorhabditis elegans strains are completely emodepside resistant. However, direct effects of emodepside on Slo-1 have not been reported and these channels have only been characterized for C. elegans and related Strongylida. Molecular and bioinformatic analyses identified full-length Slo-1 cDNAs of Ascaris suum, Parascaris equorum, Toxocara canis, Dirofilaria immitis, Brugia malayi, Onchocerca gutturosa and Strongyloides ratti. Two paralogs were identified in the trichocephalids Trichuris muris, Trichuris suis and Trichinella spiralis. Several splice variants encoding truncated channels were identified in Trichuris spp. Slo-1 channels of trichocephalids form a monophyletic group, showing that duplication occurred after the divergence of Enoplea and Chromadorea. To explore the function of a representative protein, C. elegans Slo-1a was expressed in Xenopus laevis oocytes and studied in electrophysiological (voltage-clamp experiments. Incubation of oocytes with 1-10 µM emodepside caused significantly increased currents over a wide range of step potentials in the absence of experimentally increased intracellular Ca2+, suggesting that emodepside directly opens C. elegans Slo-1a. Emodepside wash-out did not reverse the effect and the Slo-1 inhibitor verruculogen was only effective when applied before, but not after, emodepside. The identification of several splice variants and paralogs in some parasitic nematodes suggests that there are substantial differences in channel properties among species. Most importantly, this study showed for the first time that emodepside directly opens a Slo-1 channel, significantly improving the understanding of the mode of action of this drug class.

  20. Reduced KCNQ4-encoded voltage-dependent potassium channel activity underlies impaired β-adrenoceptor-mediated relaxation of renal arteries in hypertension.

    Science.gov (United States)

    Chadha, Preet S; Zunke, Friederike; Zhu, Hai-Lei; Davis, Alison J; Jepps, Thomas A; Olesen, Søren P; Cole, William C; Moffatt, James D; Greenwood, Iain A

    2012-04-01

    KCNQ4-encoded voltage-dependent potassium (Kv7.4) channels are important regulators of vascular tone that are severely compromised in models of hypertension. However, there is no information as to the role of these channels in responses to endogenous vasodilators. We used a molecular knockdown strategy, as well as pharmacological tools, to examine the hypothesis that Kv7.4 channels contribute to β-adrenoceptor-mediated vasodilation in the renal vasculature and underlie the vascular deficit in spontaneously hypertensive rats. Quantitative PCR and immunohistochemistry confirmed gene and protein expression of KCNQ1, KCNQ3, KCNQ4, KCNQ5, and Kv7.1, Kv7.4, and Kv7.5 in rat renal artery. Isoproterenol produced concentration-dependent relaxation of precontracted renal arteries and increased Kv7 channel currents in isolated smooth muscle cells. Application of the Kv7 blocker linopirdine attenuated isoproterenol-induced relaxation and current. Isoproterenol-induced relaxations were also reduced in arteries incubated with small interference RNAs targeted to KCNQ4 that produced a ≈60% decrease in Kv7.4 protein level. Relaxation to isoproterenol and the Kv7 activator S-1 were abolished in arteries from spontaneously hypertensive rats, which was associated with ≈60% decrease in Kv7.4 abundance. This study provides the first evidence that Kv7 channels contribute to β-adrenoceptor-mediated vasodilation in the renal vasculature and that abrogation of Kv7.4 channels is strongly implicated in the impaired β-adrenoceptor pathway in spontaneously hypertensive rats. These findings may provide a novel pathogenic link between arterial dysfunction and hypertension.

  1. Voltage-dependent potassium currents during fast spikes of rat cerebellar Purkinje neurons: inhibition by BDS-I toxin.

    Science.gov (United States)

    Martina, Marco; Metz, Alexia E; Bean, Bruce P

    2007-01-01

    We characterized the kinetics and pharmacological properties of voltage-activated potassium currents in rat cerebellar Purkinje neurons using recordings from nucleated patches, which allowed high resolution of activation and deactivation kinetics. Activation was exceptionally rapid, with 10-90% activation in about 400 mus at +30 mV, near the peak of the spike. Deactivation was also extremely rapid, with a decay time constant of about 300 mus near -80 mV. These rapid activation and deactivation kinetics are consistent with mediation by Kv3-family channels but are even faster than reported for Kv3-family channels in other neurons. The peptide toxin BDS-I had very little blocking effect on potassium currents elicited by 100-ms depolarizing steps, but the potassium current evoked by action potential waveforms was inhibited nearly completely. The mechanism of inhibition by BDS-I involves slowing of activation rather than total channel block, consistent with the effects described in cloned Kv3-family channels and this explains the dramatically different effects on currents evoked by short spikes versus voltage steps. As predicted from this mechanism, the effects of toxin on spike width were relatively modest (broadening by roughly 25%). These results show that BDS-I-sensitive channels with ultrafast activation and deactivation kinetics carry virtually all of the voltage-dependent potassium current underlying repolarization during normal Purkinje cell spikes.

  2. Voltage-Dependent Anion Channel 1(VDAC1) Participates the Apoptosis of the Mitochondrial Dysfunction in Desminopathy

    Science.gov (United States)

    Mo, Yanqing; Gong, Qi; Jiang, Aihua; Zhao, Jing

    2016-01-01

    Desminopathies caused by the mutation in the gene coding for desmin are genetically protein aggregation myopathies. Mitochondrial dysfunction is one of pathological changes in the desminopathies at the earliest stage. The molecular mechanisms of mitochondria dysfunction in desminopathies remain exclusive. VDAC1 regulates mitochondrial uptake across the outer membrane and mitochondrial outer membrane permeabilization (MOMP). Relationships between desminopathies and Voltage-dependent anion channel 1 (VDAC1) remain unclear. Here we successfully constructed the desminopathy rat model, evaluated with conventional stains, containing hematoxylin and eosin (HE), Gomori Trichrome (MGT), (PAS), red oil (ORO), NADH-TR, SDH staining and immunohistochemistry. Immunofluorescence results showed that VDAC1 was accumulated in the desmin highly stained area of muscle fibers of desminopathy patients or desminopathy rat model compared to the normal ones. Meanwhile apoptosis related proteins bax and ATF2 were involved in desminopathy patients and desminopathy rat model, but not bcl-2, bcl-xl or HK2.VDAC1 and desmin are closely relevant in the tissue splices of deminopathies patients and rats with desminopathy at protein lever. Moreover, apoptotic proteins are also involved in the desminopathies, like bax, ATF2, but not bcl-2, bcl-xl or HK2. This pathological analysis presents the correlation between VDAC1 and desmin, and apoptosis related proteins are correlated in the desminopathy. Furthermore, we provide a rat model of desminopathy for the investigation of desmin related myopathy. PMID:27941998

  3. Inhibitory effect of resveratrol on the proliferation of GH3 pituitary-adenoma cells and voltage-dependent potassium current

    Institute of Scientific and Technical Information of China (English)

    Ming Chu; Lanlan Wei; Chao Wang; Yu Cheng; Kongbin Yang; Baofeng Yang

    2006-01-01

    BACKGROUND:Recent researches indicate that activation of potassium channel is likely to cause many kinds of cells to proliferate and differentiate;using chemical to block the potassium channel can restrain the proliferation of small lung-cancer cells.breast cancer.prostate cancer and human lymphocyte,etc.Previous researches proved that resveratrol(RE),a selective estrogen receptor modulator(SERM).could inhibit growth of GH3 calls,induce apoptosis,and resist tumor through interfering K+ channel.OBJECTIVE:To investigate the effects of RE on Voltage-dependent K+ current [Ik(v)] and cell proliferation in GH3 pituitary-tumor cells.DESIGN:Observational contrast study.SETTING:Department of Neurosurgery.the First Clinical Hospital of Harbin Medical University;Department of Microbiology,Harbin Medical University;Department of Pharmacology,Harbin Medical University.MATERIALS: GH3 pituitary-tumor cell line of rats was purchased from the American Type Culture Collection (ATCC).RE and[3-(4,5-dimethylthiazo1-2-y1)-2.5-diphenyl-tetrazolium bromide](MTT)were obtained from Sigma Chemical CO,St Louis,USA;Ham's F-10 medium from Gibco BRL;Equine serum and fetal bovine serum from Hyclone Laboratories,Logan,UT;FACSCalibur flow cytometer from BD Company,USA.RE was dissolved in ethanol and stored at-20 ℃.It was diluted to different concentrations (10.50,100 μmol/L)with medium and extra cellular solution when needed.rhe final concentration of ethanol was Jess than 0.01%.METHODS:The experiment was carried out in the Department of Microbiology and Pharmacology of Harbin Medical University from March 2005 to January 2006.①Cell preparation:Proliferating indexes affected by 10.50 and 100 μmol/L RE were measured with MTT,respectively.0.0001 volume fraction of ethan ol was added into control group.Inhibitory rate of cellular growth was calculated as the following formula:Inhibitory rate (%)=(1-A value in experimental group/A value in control group)x100%.The experiments mentioned above were

  4. Multiphasic profiles for voltage-dependent K+ channels: Reanalysis of data of MacKinnon and coworkers

    CERN Document Server

    Nissen, Per

    2016-01-01

    In a study of the role that voltage-dependent K+ channels may have in the mechanosensation of living cells (Schmidt et al. Proc Soc Natl Acad Sci USA 109: 10352-10357. 2012), the data were as conventionally done fitted by a Boltzmann function. However, as also found for other data for ion channels, this interpretation must be rejected in favor of a multiphasic profile, a series of straight lines separated by discontinuous transitions, quite often in the form of noncontiguities (jumps). The data points in the present study are often very unevenly distributed around the curvilinear profiles. Thus, for 43 of the 75 profiles, the probability is less than 5% that the uneven distribution is due to chance, for 26 the probability is less than 1%, and for 12 the probability is less than 0.1%, giving a vanishingly low overall probability for all profiles. Especially at low voltages, the differences between the fits to curvilinear and multiphasic profiles may be huge. In the multiphasic profiles, adjacent lines are quit...

  5. Scorpion toxin prolongs an inactivation phase of the voltage-dependent sodium current in rat isolated single hippocampal neurons.

    Science.gov (United States)

    Kaneda, M; Oyama, Y; Ikemoto, Y; Akaike, N

    1989-05-15

    The effects of scorpion toxin on the voltage-dependent sodium current (INa) of CA1 pyramidal neurons isolated from rat hippocampus were studied under the single-electrode voltage-clamp condition using a 'concentration-clamp' technique. The toxin increased the peak amplitude of INa and prolonged its inactivation phase in a time- and dose-dependent manner. Inactivation phase of INa proceeded with two exponential components in the absence (control) and presence of the toxin. In the toxin-treated neurons, both the time constant of slow component and its fractional contribution to the total current increased dose-dependently while the fractional contribution of the fast one decreased in a dose-dependent fashion without changing its time constant. Actions of scorpion toxin on the sodium channels of hippocampal pyramidal neurons were essentially similar to those of peripheral preparations. Therefore, it can be concluded that the sodium channels of mammalian brain neurons have structures and functions similar to peripheral channels.

  6. Inhibition of rat hippocampal excitability by the plant alkaloid 3-acetylaconitine mediated by interaction with voltage-dependent sodium channels.

    Science.gov (United States)

    Ameri, A

    1997-02-01

    The effects of the Aconitum alkaloid 3-acetylaconitine on neuronal activity were investigated in the slice preparation and on cultivated neurons of rat hippocampus by extracellular and patch-clamp recordings, respectively. 3-Acetylaconitine (0.01-1 microM) diminished the orthodromic and antidromic population spike in a concentration-dependent manner. The inhibitory action of the drug was preceded by a transiently enhanced excitability. The latency of onset of the inhibition was accelerated by increased stimulation frequency, whereas recovery during washout of the alkaloid was accelerated by decreased stimulation frequency. Moreover, the inhibitory effect of 3-acetylaconitine was evaluated in two different models of epileptiform activity induced either by blockade of GABA receptors by bicuculline (10 microM) or by a nominal Mg(2+)-free bathing medium. In accordance with the activity-dependent mode of action, this compound abolished the synaptically evoked population spikes in the presence of bicuculline or nominal Mg(2+)-free bathing medium, respectively. Whole-cell patch-clamp recordings revealed an interaction of 3-acetylaconitine with the voltage-dependent sodium channel. At a concentration of 1 microM, 3-acetylaconitine did not affect the peak amplitude of the sodium current, but shifted the current-voltage relationship in the hyperpolarized direction such that sodium currents were already activated at the resting potential.

  7. Voltage-dependent anion channels (VDACs, porin) expressed in the plasma membrane regulate the differentiation and function of human osteoclasts.

    Science.gov (United States)

    Kotake, Shigeru; Yago, Toru; Kawamoto, Manabu; Nanke, Yuki

    2013-01-01

    Fewer molecules have been identified on human than murine osteoclasts, the former differing from murine osteoclasts in many ways. We show that voltage-dependent anion channels (VDACs, porin) are expressed in the plasma membrane of human osteoclasts. A search for novel proteins expressed in the plasma membrane of human osteoclasts identified VDAC. Anti-VDAC antibodies inhibited human osteoclastogenesis in vitro. VDAC expression was detected in membranes by immunoelectron microscopy and immunocytochemical double staining. The VDAC protein functions as a Cl(-) channel. VDACs regulate bone resorption, which show using Osteologic™ plates. The epitope of the antibody lay within a 10-amino acid sequence in the VDAC. The findings suggest that the VDAC is, at least partly, a novel Cl(-) channel regulating the differentiation and function of human osteoclasts. VDACs may play a crucial role in acidifying the resorption lacunae between osteoclasts and bone. Inhibitors of VDACs could be used to treat diseases involving increased resorption, such as osteoporosis, rheumatoid arthritis, and Paget's disease. © 2012 International Federation for Cell Biology.

  8. The voltage-dependent K+ channels Kv1.3 and Kv1.5 in human cancer

    Science.gov (United States)

    Comes, Núria; Bielanska, Joanna; Vallejo-Gracia, Albert; Serrano-Albarrás, Antonio; Marruecos, Laura; Gómez, Diana; Soler, Concepció; Condom, Enric; Ramón y Cajal, Santiago; Hernández-Losa, Javier; Ferreres, Joan C.; Felipe, Antonio

    2013-01-01

    Voltage-dependent K+ channels (Kv) are involved in a number of physiological processes, including immunomodulation, cell volume regulation, apoptosis as well as differentiation. Some Kv channels participate in the proliferation and migration of normal and tumor cells, contributing to metastasis. Altered expression of Kv1.3 and Kv1.5 channels has been found in several types of tumors and cancer cells. In general, while the expression of Kv1.3 apparently exhibits no clear pattern, Kv1.5 is induced in many of the analyzed metastatic tissues. Interestingly, evidence indicates that Kv1.5 channel shows inversed correlation with malignancy in some gliomas and non-Hodgkin's lymphomas. However, Kv1.3 and Kv1.5 are similarly remodeled in some cancers. For instance, expression of Kv1.3 and Kv1.5 correlates with a certain grade of tumorigenicity in muscle sarcomas. Differential remodeling of Kv1.3 and Kv1.5 expression in human cancers may indicate their role in tumor growth and their importance as potential tumor markers. However, despite of this increasing body of information, which considers Kv1.3 and Kv1.5 as emerging tumoral markers, further research must be performed to reach any conclusion. In this review, we summarize what it has been lately documented about Kv1.3 and Kv1.5 channels in human cancer. PMID:24133455

  9. The voltage-dependent K(+) channels Kv1.3 and Kv1.5 in human cancer.

    Science.gov (United States)

    Comes, Núria; Bielanska, Joanna; Vallejo-Gracia, Albert; Serrano-Albarrás, Antonio; Marruecos, Laura; Gómez, Diana; Soler, Concepció; Condom, Enric; Ramón Y Cajal, Santiago; Hernández-Losa, Javier; Ferreres, Joan C; Felipe, Antonio

    2013-10-10

    Voltage-dependent K(+) channels (Kv) are involved in a number of physiological processes, including immunomodulation, cell volume regulation, apoptosis as well as differentiation. Some Kv channels participate in the proliferation and migration of normal and tumor cells, contributing to metastasis. Altered expression of Kv1.3 and Kv1.5 channels has been found in several types of tumors and cancer cells. In general, while the expression of Kv1.3 apparently exhibits no clear pattern, Kv1.5 is induced in many of the analyzed metastatic tissues. Interestingly, evidence indicates that Kv1.5 channel shows inversed correlation with malignancy in some gliomas and non-Hodgkin's lymphomas. However, Kv1.3 and Kv1.5 are similarly remodeled in some cancers. For instance, expression of Kv1.3 and Kv1.5 correlates with a certain grade of tumorigenicity in muscle sarcomas. Differential remodeling of Kv1.3 and Kv1.5 expression in human cancers may indicate their role in tumor growth and their importance as potential tumor markers. However, despite of this increasing body of information, which considers Kv1.3 and Kv1.5 as emerging tumoral markers, further research must be performed to reach any conclusion. In this review, we summarize what it has been lately documented about Kv1.3 and Kv1.5 channels in human cancer.

  10. Actin Dynamics Regulates Voltage-Dependent Calcium-Permeable Channels of the Vicia faba Guard Cell Plasma Membrane

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Liu-Min Fan

    2009-01-01

    Free cytosolic Ca~(2+) ([Ca~(2+)]_(cyt)) is an ubiquitous second messenger in plant cell signaling, and [Ca~(2+)]_(cyt) elevation is associated with Ca~(2+)-permeable channels in the plasma membrane and endomembranes regulated by a wide range of stimuli. However, knowledge regarding Ca~(2+) channels and their regulation remains limited in planta. A type of voltage-dependent Ca~(2+)-permeable channel was identified and characterized for the Vicia faba L. guard cell plasma membrane by using patch-clamp techniques. These channels are permeable to both Ba~(2+) and Ca~(2+), and their activities can be inhibited by micromolar Gd~(3+). The unitary conductance and the reversal potential of the channels depend on the Ca~(2+) or Ba~(2+) gradients across the plasma membrane. The inward whole-cell Ca~(2+) (Ba~(2+)) current, as well as the unitary current amplitude and NP. of the single Ca~(2+) channel, increase along with the membrane hyperpolarization. Pharmacological experiments suggest that actin dynamics may serve as an upstream regulator of this type of calcium channel of the guard cell plasma membrane. Cytochalasin D, an actin polymerization blocker, activated the NP_o of these channels at the single channel level and increased the current amplitude at the whole-cell level. But these channel activations and current increments could be restrained by pretreatment with an F-actin stabilizer, phalloidin. The potential physiological significance of this regulatory mechanism is also discussed.

  11. Voltage-dependent anion channels modulate mitochondrial metabolism in cancer cells: regulation by free tubulin and erastin.

    Science.gov (United States)

    Maldonado, Eduardo N; Sheldon, Kely L; DeHart, David N; Patnaik, Jyoti; Manevich, Yefim; Townsend, Danyelle M; Bezrukov, Sergey M; Rostovtseva, Tatiana K; Lemasters, John J

    2013-04-26

    Respiratory substrates and adenine nucleotides cross the mitochondrial outer membrane through the voltage-dependent anion channel (VDAC), comprising three isoforms--VDAC1, 2, and 3. We characterized the role of individual isoforms in mitochondrial metabolism by HepG2 human hepatoma cells using siRNA. With VDAC3 to the greatest extent, all VDAC isoforms contributed to the maintenance of mitochondrial membrane potential, but only VDAC3 knockdown decreased ATP, ADP, NAD(P)H, and mitochondrial redox state. Cells expressing predominantly VDAC3 were least sensitive to depolarization induced by increased free tubulin. In planar lipid bilayers, free tubulin inhibited VDAC1 and VDAC2 but not VDAC3. Erastin, a compound that interacts with VDAC, blocked and reversed mitochondrial depolarization after microtubule destabilizers in intact cells and antagonized tubulin-induced VDAC blockage in planar bilayers. In conclusion, free tubulin inhibits VDAC1/2 and limits mitochondrial metabolism in HepG2 cells, contributing to the Warburg phenomenon. Reversal of tubulin-VDAC interaction by erastin antagonizes Warburg metabolism and restores oxidative mitochondrial metabolism.

  12. Dopamine Induces LTP Differentially in Apical and Basal Dendrites through BDNF and Voltage-Dependent Calcium Channels

    Science.gov (United States)

    Navakkode, Sheeja; Sajikumar, Sreedharan; Korte, Martin; Soong, Tuck Wah

    2012-01-01

    The dopaminergic modulation of long-term potentiation (LTP) has been studied well, but the mechanism by which dopamine induces LTP (DA-LTP) in CA1 pyramidal neurons is unknown. Here, we report that DA-LTP in basal dendrites is dependent while in apical dendrites it is independent of activation of L-type voltage-gated calcium channels (VDCC).…

  13. Dopamine Induces LTP Differentially in Apical and Basal Dendrites through BDNF and Voltage-Dependent Calcium Channels

    Science.gov (United States)

    Navakkode, Sheeja; Sajikumar, Sreedharan; Korte, Martin; Soong, Tuck Wah

    2012-01-01

    The dopaminergic modulation of long-term potentiation (LTP) has been studied well, but the mechanism by which dopamine induces LTP (DA-LTP) in CA1 pyramidal neurons is unknown. Here, we report that DA-LTP in basal dendrites is dependent while in apical dendrites it is independent of activation of L-type voltage-gated calcium channels (VDCC).…

  14. Expression and localization of voltage dependent potassium channel Kv4.2 in epilepsy associated focal lesions

    NARCIS (Netherlands)

    Aronica, E.; Boer, K.; Doorn, K.J.; Zurolo, E.; Spliet, W.G.M.; van Rijen, P.C.; Baayen, J.C.; Gorter, J.A.; Jeromin, A.

    2009-01-01

    An increasing number of observations suggest an important role for voltage-gated potassium (Kv) channels in epilepsy. We studied the cell-specific distribution of Kv4.2, phosphorylated (p) Kv4.2 and the Kv4.2 interacting protein NCS-1 using immunocytochemistry in different epilepsy-associated focal

  15. Expression and localization of voltage dependent potassium channel Kv4.2 in epilepsy associated focal lesions

    NARCIS (Netherlands)

    Aronica, E.; Boer, K.; Doorn, K.J.; Zurolo, E.; Spliet, W.G.M.; van Rijen, P.C.; Baayen, J.C.; Gorter, J.A.; Jeromin, A.

    2009-01-01

    An increasing number of observations suggest an important role for voltage-gated potassium (Kv) channels in epilepsy. We studied the cell-specific distribution of Kv4.2, phosphorylated (p) Kv4.2 and the Kv4.2 interacting protein NCS-1 using immunocytochemistry in different epilepsy-associated focal

  16. Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart

    NARCIS (Netherlands)

    Schultz, D; Mikala, G; Yatani, A; Engle, D B; Iles, D E; Segers, B; Sinke, R J; Weghuis, D O; Klöckner, U; Wakamori, M

    1993-01-01

    A unique structural variant of the cardiac L-type voltage-dependent calcium channel alpha 1 subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows significant homology to other calcium channel alpha 1 subunits. However, differences from t

  17. Lack of negatively charged residues at the external mouth of Kir2.2 channels enable the voltage-dependent block by external Mg2+.

    Directory of Open Access Journals (Sweden)

    Junwei Li

    Full Text Available Kir channels display voltage-dependent block by cytosolic cations such as Mg2+ and polyamines that causes inward rectification. In fact, cations can regulate K channel activity from both the extracellular and intracellular sides. Previous studies have provided insight into the up-regulation of Kir channel activity by extracellular K+ concentration. In contrast, extracellular Mg2+ has been found to reduce the amplitude of the single-channel current at milimolar concentrations. However, little is known about the molecular mechanism of Kir channel blockade by external Mg2+ and the relationship between the Mg2+ blockade and activity potentiation by permeant K+ ions. In this study, we applied an interactive approach between theory and experiment. Electrophysiological recordings on Kir2.2 and its mutants were performed by heterologous expression in Xenopus laevis oocytes. Our results confirmed that extracellular Mg2+ could reduce heterologously expressed WT Kir2.2 currents in a voltage dependent manner. The kinetics of inhibition and recovery of Mg2+ exhibit a 3∼4s time constant. Molecular dynamics simulation results revealed a Mg2+ binding site located at the extracellular mouth of Kir2.2 that showed voltage-dependent Mg2+ binding. The mutants, G119D, Q126E and H128D, increased the number of permeant K+ ions and reduced the voltage-dependent blockade of Kir2.2 by extracellular Mg2+.

  18. Altered ischemic cerebral injury in mice lacking αIE subunit of the voltage-dependent Ca2+ channel

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective ①To set up a stable and reproducible focal cerebral infarct modelin mice; (②To examine theinvolvement of αIE subunit of voltage-dependent Ca2 + channel in cerebral ischemic injury. Methods Male C57BL/6J Jclmice 8 ~ 12w and F4 ~ F6αIE subunit of Ca2+ channel mutant mice were both used in this study. All animals were allowedto freely access to food and water before and after operation. Animals were anesthetized with pentobarbital sodium 60mg/kg,ip. Rectal temperature was continuously monitored before, during and after operation, and maintained at (36.6 +0.1 )°C by a autoregulating pad. To produce pilot models, the middle cerebral artery (MCA) was occluded either by sur-gical ligation or electrical coagulation and in some models the common carotid artery (CCA) was surgically ligated in tan-dem. In our latter work the MCA was cut off soon after it was ligated or coagulated in order to make sure that the bloodflow was occluded completely. The MCA was coagulated or ligated with a bipolar coagulator or microsurgery suture at thesite just superior to the rhinal fissure. Twenty~four hours after the operation, the mice were anesthetized and decapitated,then their brains were dissected from the skull and put into cold artificial brain spinal fluid as soon as possible. Lmm thickcoronal sections were cut by vibratome and stained with 2% 2,3,5-triphenyltetrazolium chloride (TTC) at 37°C for30min. Every section was photographed positively and the whole infarction volume was calculated by summing up the in-farction volumes of all sections by NIH Image System. Infarction ratio ( % ) was also calculated by the following fommula:(contralateral volume-ipsilateral undamaged volume)/contralateral volume × 100% to eliminate the influence of edema.In brief, the mutant mice were produced with gene targeting technique. F4 ~ F6 mice were used in this experiment. Alloffsprings were genotyped by the polymerase chain reaction (PCR) and the genotypes remained umknown

  19. Voltage dependence of Hodgkin-Huxley rate functions for a multistage K^{+} channel voltage sensor within a membrane.

    Science.gov (United States)

    Vaccaro, S R

    2014-11-01

    The activation of a K^{+} channel sensor in two sequential stages during a voltage clamp may be described as the translocation of a Brownian particle in an energy landscape with two large barriers between states. A solution of the Smoluchowski equation for a square-well approximation to the potential function of the S4 voltage sensor satisfies a master equation and has two frequencies that may be determined from the forward and backward rate functions. When the higher-frequency terms have small amplitude, the solution reduces to the relaxation of a rate equation, where the derived two-state rate functions are dependent on the relative magnitude of the forward rates (α and γ) and the backward rates (β and δ) for each stage. In particular, the voltage dependence of the Hodgkin-Huxley rate functions for a K^{+} channel may be derived by assuming that the rate functions of the first stage are large relative to those of the second stage-α≫γ and β≫δ. For a Shaker IR K^{+} channel, the first forward and backward transitions are rate limiting (αchannel and a noninactivating Na^{+} ion channel is determined by the master equation for K^{+} channel activation and the ionic current equation when the Na^{+} channel activation time is small, and if β≪δ and α≪γ, the system may exhibit a small amplitude oscillation between spikes, or mixed-mode oscillation, in which the slow closed state modulates the K^{+} ion channel conductance in the membrane.

  20. Voltage-dependent ionic channels in differentiating neural precursor cells collected from adult mouse brains six hours post-mortem.

    Science.gov (United States)

    Bellardita, Carmelo; Bolzoni, Francesco; Sorosina, Melissa; Marfia, Giovanni; Carelli, Stephana; Gorio, Alfredo; Formenti, Alessandro

    2012-04-01

    A novel type of adult neural precursor cells (NPCs) has been isolated from the subventricular zone of the mouse 6 hr after animal death (T6-NPCs). This condition is supposed to select hypoxia-resistant cells of scientific and clinical interest. Ionic channels are ultimately the expression of the functional maturation of neurons, so the aim of this research was to characterize the pattern of the main voltage-dependent ionic channels in T6-NPCs differentiating to a neuronal phenotype, comparing it with NPCs isolated soon after death (T0-NPCs). T6- and T0-NPCs grow in medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Differentiation was performed in small wells without the addition of growth factors, in the presence of adhesion molecules, fetal bovine serum, and leukemia inhibitory factor. Ionic currents, recorded by means of whole-cell patch-clamp, namely, I(Ca2+) HVA, both L- and non-L-type, I(K+) delayed rectifying, I(K+) inward rectifier, transient I(K+A) , and TTX-sensitive I(Na+) have been found, although Na(+) currents were found in only a small percentage of cells and after the fifth week of differentiation. No significant differences in current types, density, orcell capacitance were observed between T6-NPCs and T0-NPCs. The sequence in which the markers appear in new neural cells is not necessarily a fixed program, but the discrepancies in morphological, biochemical, and electrophysiological maturation of mouse NPCs to neurons, possibly different in vivo, suggest that the various steps of the differentiation are independently regulated. Therefore, in addition to morphological and biochemical data, functional tests should be considered for characterizing the maturation of neurons.

  1. The Voltage-dependent Anion Channel 1 Mediates Amyloid β Toxicity and Represents a Potential Target for Alzheimer Disease Therapy.

    Science.gov (United States)

    Smilansky, Angela; Dangoor, Liron; Nakdimon, Itay; Ben-Hail, Danya; Mizrachi, Dario; Shoshan-Barmatz, Varda

    2015-12-25

    The voltage-dependent anion channel 1 (VDAC1), found in the mitochondrial outer membrane, forms the main interface between mitochondrial and cellular metabolisms, mediates the passage of a variety of molecules across the mitochondrial outer membrane, and is central to mitochondria-mediated apoptosis. VDAC1 is overexpressed in post-mortem brains of Alzheimer disease (AD) patients. The development and progress of AD are associated with mitochondrial dysfunction resulting from the cytotoxic effects of accumulated amyloid β (Aβ). In this study we demonstrate the involvement of VDAC1 and a VDAC1 N-terminal peptide (VDAC1-N-Ter) in Aβ cell penetration and cell death induction. Aβ directly interacted with VDAC1 and VDAC1-N-Ter, as monitored by VDAC1 channel conductance, surface plasmon resonance, and microscale thermophoresis. Preincubated Aβ interacted with bilayer-reconstituted VDAC1 and increased its conductance ∼ 2-fold. Incubation of cells with Aβ resulted in mitochondria-mediated apoptotic cell death. However, the presence of non-cell-penetrating VDAC1-N-Ter peptide prevented Aβ cellular entry and Aβ-induced mitochondria-mediated apoptosis. Likewise, silencing VDAC1 expression by specific siRNA prevented Aβ entry into the cytosol as well as Aβ-induced toxicity. Finally, the mode of Aβ-mediated action involves detachment of mitochondria-bound hexokinase, induction of VDAC1 oligomerization, and cytochrome c release, a sequence of events leading to apoptosis. As such, we suggest that Aβ-mediated toxicity involves mitochondrial and plasma membrane VDAC1, leading to mitochondrial dysfunction and apoptosis induction. The VDAC1-N-Ter peptide targeting Aβ cytotoxicity is thus a potential new therapeutic strategy for AD treatment.

  2. Thiazolidinedione insulin sensitizers alter lipid bilayer properties and voltage-dependent sodium channel function: implications for drug discovery.

    Science.gov (United States)

    Rusinova, Radda; Herold, Karl F; Sanford, R Lea; Greathouse, Denise V; Hemmings, Hugh C; Andersen, Olaf S

    2011-08-01

    The thiazolidinediones (TZDs) are used in the treatment of diabetes mellitus type 2. Their canonical effects are mediated by activation of the peroxisome proliferator-activated receptor γ (PPARγ) transcription factor. In addition to effects mediated by gene activation, the TZDs cause acute, transcription-independent changes in various membrane transport processes, including glucose transport, and they alter the function of a diverse group of membrane proteins, including ion channels. The basis for these off-target effects is unknown, but the TZDs are hydrophobic/amphiphilic and adsorb to the bilayer-water interface, which will alter bilayer properties, meaning that the TZDs may alter membrane protein function by bilayer-mediated mechanisms. We therefore explored whether the TZDs alter lipid bilayer properties sufficiently to be sensed by bilayer-spanning proteins, using gramicidin A (gA) channels as probes. The TZDs altered bilayer elastic properties with potencies that did not correlate with their affinity for PPARγ. At concentrations where they altered gA channel function, they also altered the function of voltage-dependent sodium channels, producing a prepulse-dependent current inhibition and hyperpolarizing shift in the steady-state inactivation curve. The shifts in the inactivation curve produced by the TZDs and other amphiphiles can be superimposed by plotting them as a function of the changes in gA channel lifetimes. The TZDs' partition coefficients into lipid bilayers were measured using isothermal titration calorimetry. The most potent bilayer modifier, troglitazone, alters bilayer properties at clinically relevant free concentrations; the least potent bilayer modifiers, pioglitazone and rosiglitazone, do not. Unlike other TZDs tested, ciglitazone behaves like a hydrophobic anion and alters the gA monomer-dimer equilibrium by more than one mechanism. Our results provide a possible mechanism for some off-target effects of an important group of drugs, and

  3. Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1.

    Science.gov (United States)

    Budelier, Melissa M; Cheng, Wayland W L; Bergdoll, Lucie; Chen, Zi-Wei; Janetka, James W; Abramson, Jeff; Krishnan, Kathiresan; Mydock-McGrane, Laurel; Covey, Douglas F; Whitelegge, Julian P; Evers, Alex S

    2017-06-02

    Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI-tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr(83) and Glu(73), respectively. When Glu(73) was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr(62) within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu(73) residue. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Voltage-dependent changes in specific membrane capacitance caused by prestin, the outer hair cell lateral membrane motor.

    Science.gov (United States)

    Santos-Sacchi, Joseph; Navarrete, Enrique

    2002-05-01

    In the outer hair cell (OHC), membrane capacitance principally derives from two components - that associated with lateral membrane sensor/motor charge movement, and that proportional to the membrane surface area (C(sa)). We used measures of membrane capacitance to test a model hypothesis that OHC lateral membrane molecular motors, recently identified as the protein prestin, fluctuate between two area states. By measuring membrane capacitance in native OHCs or prestin-transfected HEK cells at extreme voltages (+/-200 mV) where motor-derived charge movement is small or absent, we observed that C(sa) depends on the state of the motors, or correspondingly on membrane voltage. Deiters cells or control HEK cells, which lack motors, do not show this dependence. We modeled the voltage-dependent change in C(sa) as a Boltzmann process with the same parameters that describe the charge movement of the motors' voltage sensors. C(sa) is 3.28+/-0.75 pF (mean +/-SD; n=23) larger during extreme hyperpolarization, and the number of motors in OHCs and prestin-transfected HEK cells correlates with the magnitude of Delta C(sa)( r=0.78). Although these data are consistent with the area motor model, the corresponding area change, assuming 0.5 microF/cm(2) under constant membrane thickness, is unphysiologically large, and indicates that the capacitance change must result from changes not only in lateral membrane area but also specific capacitance. Thus, we conclude that a conformational change in the lateral membrane motor, prestin, additionally alters the dielectric constant and/or thickness of the lateral plasma membrane.

  5. Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats.

    Science.gov (United States)

    Belugin, Sergei; Mifflin, Steve

    2005-12-01

    Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltage-dependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P NTS neurons from NT and HT rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P = 0.016 and P = 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P = 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension.

  6. Ion channel gating a first passage time analysis of the Kramers type

    CERN Document Server

    Goychuk, I; Goychuk, Igor

    2001-01-01

    The opening rate of voltage-gated potassium ion channels exhibits a characteristic, knee-like turnover where the common exponential voltage-dependence changes suddenly into a linear one. An explanation of this puzzling crossover is put forward in terms of a stochastic first passage time analysis. The theory predicts that the exponential voltage-dependence correlates with the exponential distribution of closed residence times. This feature occurs at large negative voltages when the channel is predominantly closed. In contrast, the linear part of voltage-dependence emerges together with a non-exponential distribution of closed dwelling times with increasing voltage, yielding a large opening rate. Depending on the parameter set, the closed-time distribution displays a power law behavior which extends over several decades.

  7. Ion channel gating: A first-passage time analysis of the Kramers type

    Science.gov (United States)

    Goychuk, Igor; Hänggi, Peter

    2002-03-01

    The opening rate of voltage-gated potassium ion channels exhibits a characteristic knee-like turnover where the common exponential voltage dependence changes suddenly into a linear one. An explanation of this puzzling crossover is put forward in terms of a stochastic first passage time analysis. The theory predicts that the exponential voltage dependence correlates with the exponential distribution of closed residence times. This feature occurs at large negative voltages when the channel is predominantly closed. In contrast, the linear part of voltage dependence emerges together with a nonexponential distribution of closed dwelling times with increasing voltage, yielding a large opening rate. Depending on the parameter set, the closed-time distribution displays a power law behavior that extends over several decades.

  8. The ladder-shaped polyether toxin gambierol anchors the gating machinery of Kv3.1 channels in the resting state.

    Science.gov (United States)

    Kopljar, Ivan; Labro, Alain J; de Block, Tessa; Rainier, Jon D; Tytgat, Jan; Snyders, Dirk J

    2013-03-01

    Voltage-gated potassium (Kv) and sodium (Nav) channels are key determinants of cellular excitability and serve as targets of neurotoxins. Most marine ciguatoxins potentiate Nav channels and cause ciguatera seafood poisoning. Several ciguatoxins have also been shown to affect Kv channels, and we showed previously that the ladder-shaped polyether toxin gambierol is a potent Kv channel inhibitor. Most likely, gambierol acts via a lipid-exposed binding site, located outside the K(+) permeation pathway. However, the mechanism by which gambierol inhibits Kv channels remained unknown. Using gating and ionic current analysis to investigate how gambierol affected S6 gate opening and voltage-sensing domain (VSD) movements, we show that the resting (closed) channel conformation forms the high-affinity state for gambierol. The voltage dependence of activation was shifted by >120 mV in the depolarizing direction, precluding channel opening in the physiological voltage range. The (early) transitions between the resting and the open state were monitored with gating currents, and provided evidence that strong depolarizations allowed VSD movement up to the activated-not-open state. However, for transition to the fully open (ion-conducting) state, the toxin first needed to dissociate. These dissociation kinetics were markedly accelerated in the activated-not-open state, presumably because this state displayed a much lower affinity for gambierol. A tetrameric concatemer with only one high-affinity binding site still displayed high toxin sensitivity, suggesting that interaction with a single binding site prevented the concerted step required for channel opening. We propose a mechanism whereby gambierol anchors the channel's gating machinery in the resting state, requiring more work from the VSD to open the channel. This mechanism is quite different from the action of classical gating modifier peptides (e.g., hanatoxin). Therefore, polyether toxins open new opportunities in structure

  9. Effects of electrolyte gating on photoluminescence spectra of large-area WSe2monolayer films

    KAUST Repository

    Matsuki, Keiichiro

    2016-05-24

    We fabricated electric double-layer transistors comprising large-area WSe2 monolayers and investigated the effects of electrolyte gating on their photoluminescence (PL) spectra. Using the efficient gating effects of electric double layers, we succeeded in the application of a large electric field (>107Vcm%1) and the accumulation of high carrier density (>1013cm%2). As a result, we observed PL spectra based on both positively and negatively charged excitons and their gate-voltage-dependent redshifts, suggesting the effects of both an electric field and charge accumulation. © 2016 The Japan Society of Applied Physics.

  10. Temperature and voltage dependence of barrier height and ideality factor in Au/0.07 graphene-doped PVA/n-Si structures

    Science.gov (United States)

    Altındal Yerişkin, S.; Balbaşı, M.; Demirezen, S.

    2017-01-01

    In this study, Au/0.07 graphene-doped PVA/n-Si structures were fabricated and current conduction mechanism in these structures were investigated in the temperature range of 80-380 K through forward bias current-voltage (I-V) measurements. Main electrical parameters were extracted from I-V data. Zero-bias barrier height (overline{Φ}_{B0} ) and ideality factor (n) were found strong functions of temperature and their values ranged from 0.234 eV and 4.98 (at 80 K) to 0.882 eV and 1.15 (at 380 K), respectively. Φ ap versus q/2kT plot was drawn to obtain an evidence of a Gaussian distribution of the barrier heights (BHs) and it revealed two distinct linear regions with different slopes and intercepts. The mean values of BH (Φ Bo) and zero-bias standard deviation (σ s ) were obtained from the intercept and slope of the linear regions of this plot as 1.30 eV and 0.16 V for the first region (280-380 K) and 0.74 eV and 0.085 V for the second region (80-240 K), respectively. Thus, the values of overline{Φ}_{B0} and effective Richardson constant (A*) were also found from the intercept and slope of the modified Richardson plot [ln(I s /T 2) - q 2 σ {/o 2} /2k 2 T 2 vs q/kT] as 1.31 eV and 130 A/cm2 K2 for the first region and 0.76 eV and 922 A/cm2 K2 for the second region, respectively. The value of A* for the first region was very close to the theoretical value for n-Si (112 A/cm2 K2). The energy density distribution profile of surface states (Nss) was also extracted from the forward bias I-V data by taking into account voltage dependent effective BH (Φe) and n.

  11. Electrostatic doping limits and control of magnetism in electrolyte gated LaAlO3(001)/La0.5Sr0.5CoO3-δ thin films

    Science.gov (United States)

    Walter, Jeff; Wang, Helin; Leighton, Chris

    Recently developed ionic liquid/gel gating techniques have proven remarkably expedient in the study of charge density effects in a variety of conductors, ranging from organics to complex oxides. Here we present electrolyte gate control of magnetism in ultrathin (8 u.c.) La0.5Sr0.5CoO3-δ (LSCO) films, using ion gels in electric double layer transistors. The LSCO films are initially metallic and ferromagnetic (Tc ~ 170 K), with anomalous Hall conductivity up to 40 S/cm, and strong perpendicular magnetic anisotropy. Based on extensive temperature and gate voltage dependences we first determined the limits for electrostatic vs. electrochemical operation, concluding that negative bias enables reversible hole accumulation, whereas positive bias irreversibly induces oxygen vacancies. Following this we demonstrated clear voltage-control of resistivity, magnetoresistance, andTc. Utilizing the anomalous Hall conductivity as an exceptional probe of the magnetic order parameter in the gated surface region, a 12 K shift in Tc is obtained. This compares favorably to the state-of-the-art and exhibits potential for much larger modulation in films of lower Sr content. Work supported by NSF MRSEC.

  12. Time-resolved photoluminescence measurements for determining voltage-dependent charge-separation efficiencies of subcells in triple-junction solar cells

    Science.gov (United States)

    Tex, David M.; Ihara, Toshiyuki; Akiyama, Hidefumi; Imaizumi, Mitsuru; Kanemitsu, Yoshihiko

    2015-01-01

    Conventional external quantum-efficiency measurement of solar cells provides charge-collection efficiency for approximate short-circuit conditions. Because this differs from actual operating voltages, the optimization of high-quality tandem solar cells is especially complicated. Here, we propose a contactless method, which allows for the determination of the voltage dependence of charge-collection efficiency for each subcell independently. By investigating the power dependence of photoluminescence decays, charge-separation and recombination-loss time constants are obtained. The upper limit of the charge-collection efficiencies at the operating points is then obtained by applying the uniform field model. This technique may complement electrical characterization of the voltage dependence of charge collection, since subcells are directly accessible.

  13. Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels

    Directory of Open Access Journals (Sweden)

    Mohamed-Yassine eAMAROUCH

    2015-02-01

    Full Text Available Voltage-gated sodium channels (Nav are widely expressed as macro-molecular complexes in both excitable and non-excitable tissues. In excitable tissues, the upstroke of the action potential is the result of the passage of a large and rapid influx of sodium ions through these channels. NaV dysfunction has been associated with an increasingly wide range of neurological, muscular and cardiac disorders. The purpose of this review is to summarize the recently identified sodium channel mutations that are linked to hyper-excitability phenotypes and associated with the alteration of the activation process of voltage gated sodium channels. Indeed, several clinical manifestations that demonstrate an alteration of tissue excitability were recently shown to be strongly associated with the presence of mutations that affect the activation process of the voltage-gated sodium channels. These emerging genotype-phenotype correlations have expanded the clinical spectrum of sodium channelopathies to include disorders which feature a hyper-excitability phenotype that may or may not be associated with a cardiomyopathy. The p.I141V mutation in SCN4A and SCN5A, as well as its homologous p.I136V mutation in SCN9A, are interesting examples of mutations that have been linked to inherited hyperexcitability myotonia, exercise-induced polymorphic ventricular arrhythmias and erythromelalgia, respectively. Regardless of which sodium channel isoform is investigated, the substitution of the isoleucine to valine in the locus 141 induces similar modifications in the biophysical properties of the voltage-gated sodium channels by shifting the voltage-dependence of steady state activation towards more negative potentials.

  14. Allosteric gating mechanism underlies the flexible gating of KCNQ1 potassium channels.

    Science.gov (United States)

    Osteen, Jeremiah D; Barro-Soria, Rene; Robey, Seth; Sampson, Kevin J; Kass, Robert S; Larsson, H Peter

    2012-05-01

    KCNQ1 (Kv7.1) is a unique member of the superfamily of voltage-gated K(+) channels in that it displays a remarkable range of gating behaviors tuned by coassembly with different β subunits of the KCNE family of proteins. To better understand the basis for the biophysical diversity of KCNQ1 channels, we here investigate the basis of KCNQ1 gating in the absence of β subunits using voltage-clamp fluorometry (VCF). In our previous study, we found the kinetics and voltage dependence of voltage-sensor movements are very similar to those of the channel gate, as if multiple voltage-sensor movements are not required to precede gate opening. Here, we have tested two different hypotheses to explain KCNQ1 gating: (i) KCNQ1 voltage sensors undergo a single concerted movement that leads to channel opening, or (ii) individual voltage-sensor movements lead to channel opening before all voltage sensors have moved. Here, we find that KCNQ1 voltage sensors move relatively independently, but that the channel can conduct before all voltage sensors have activated. We explore a KCNQ1 point mutation that causes some channels to transition to the open state even in the absence of voltage-sensor movement. To interpret these results, we adopt an allosteric gating scheme wherein KCNQ1 is able to transition to the open state after zero to four voltage-sensor movements. This model allows for widely varying gating behavior, depending on the relative strength of the opening transition, and suggests how KCNQ1 could be controlled by coassembly with different KCNE family members.

  15. Quantum entanglement in the voltage dependent sodium channel can reproduce the salient features of neuronal action potential initiation

    CERN Document Server

    Summhammer, Johann

    2007-01-01

    We investigate the effects of a quantum entanglement regime within an ion conducting molecule (ion channel) of the neuronal plasma membrane on the onset dynamics of propagating nerve pulses (action potentials). In particular, we model the onset parameters of the sodium current in the Hodgkin Huxley equation as three similar but independent probabilistic mechanisms which become quantum entangled. The underlying physics is general and can involve entanglement between various degrees of freedom underlaying ion transition states or 'gating states' during conduction, e.g. Na$^+$ ions in different channel locations, or different 'affinity' states of ions with atoms lining the sub-regions of the channel protein ('filter-states'). We find that the 'quantum corrected' Hodgkin Huxley equation incorporating entangled systems states can reproduce action potential pulses with the critical onset dynamics observed recently in neocortical neurons in vivo by Naundorf et al. [Nature {\\bf 440}, 1060 (20 April 2006)]. Interestin...

  16. Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13.

    Science.gov (United States)

    Minassian, Natali A; Lin, Meng-Chin A; Papazian, Diane M

    2012-04-01

    Mutations in Kv3.3 cause spinocerebellar ataxia type 13 (SCA13). Depending on the causative mutation, SCA13 is either a neurodevelopmental disorder that is evident in infancy or a progressive neurodegenerative disease that emerges during adulthood. Previous studies did not clarify the relationship between these distinct clinical phenotypes and the effects of SCA13 mutations on Kv3.3 function. The F448L mutation alters channel gating and causes early-onset SCA13. R420H and R423H suppress Kv3 current amplitude by a dominant negative mechanism. However, R420H results in the adult form of the disease whereas R423H produces the early-onset, neurodevelopmental form with significant clinical overlap with F448L. Since individuals with SCA13 have one wild type and one mutant allele of the Kv3.3 gene, we analysed the properties of tetrameric channels formed by mixtures of wild type and mutant subunits. We report that one R420H subunit and at least one R423H subunit can co-assemble with the wild type protein to form active channels. The functional properties of channels containing R420H and wild type subunits strongly resemble those of wild type alone. In contrast, channels containing R423H and wild type subunits show significantly altered gating, including a hyperpolarized shift in the voltage dependence of activation, slower activation, and modestly slower deactivation. Notably, these effects resemble the modified gating seen in channels containing a mixture of F448L and wild type subunits, although the F448L subunit slows deactivation more dramatically than the R423H subunit. Our results suggest that the clinical severity of R423H reflects its dual dominant negative and dominant gain of function effects. However, as shown by R420H, reducing current amplitude without altering gating does not result in infant onset disease. Therefore, our data strongly suggest that changes in Kv3.3 gating contribute significantly to an early age of onset in SCA13.

  17. The position of the fast-inactivation gate during lidocaine block of voltage-gated Na+ channels.

    Science.gov (United States)

    Vedantham, V; Cannon, S C

    1999-01-01

    Lidocaine produces voltage- and use-dependent inhibition of voltage-gated Na+ channels through preferential binding to channel conformations that are normally populated at depolarized potentials and by slowing the rate of Na+ channel repriming after depolarizations. It has been proposed that the fast-inactivation mechanism plays a crucial role in these processes. However, the precise role of fast inactivation in lidocaine action has been difficult to probe because gating of drug-bound channels does not involve changes in ionic current. For that reason, we employed a conformational marker for the fast-inactivation gate, the reactivity of a cysteine substituted at phenylalanine 1304 in the rat adult skeletal muscle sodium channel alpha subunit (rSkM1) with [2-(trimethylammonium)ethyl]methanethiosulfonate (MTS-ET), to determine the position of the fast-inactivation gate during lidocaine block. We found that lidocaine does not compete with fast-inactivation. Rather, it favors closure of the fast-inactivation gate in a voltage-dependent manner, causing a hyperpolarizing shift in the voltage dependence of site 1304 accessibility that parallels a shift in the steady state availability curve measured for ionic currents. More significantly, we found that the lidocaine-induced slowing of sodium channel repriming does not result from a slowing of recovery of the fast-inactivation gate, and thus that use-dependent block does not involve an accumulation of fast-inactivated channels. Based on these data, we propose a model in which transitions along the activation pathway, rather than transitions to inactivated states, play a crucial role in the mechanism of lidocaine action.

  18. Potentiation of glycine-gated NR1/NR3A NMDA receptors relieves Ca2+-dependent outward rectification

    Directory of Open Access Journals (Sweden)

    Christian Madry

    2010-03-01

    Full Text Available Glycine has diverse functions within the mammalian central nervous system. It inhibits postsynaptic neurons via strychnine-sensitive glycine receptors (GlyRs and enhances neuronal excitation through co-activation of N-methyl-D-aspartate (NMDA receptors. Classical Ca2+-permeable NMDA receptors are composed of glycine-binding NR1 and glutamate-binding NR2 subunits, and hence require both glutamate and glycine for efficient activation. In contrast, recombinant receptors composed of NR1 and the glycine binding NR3A and/or NR3B subunits lack glutamate binding sites and can be activated by glycine alone. Therefore these receptors are also named excitatory glycine receptors. Co-application of antagonists of the NR1 glycine-binding site or of the divalent cation Zn2+ markedly enhances the glycine responses of these receptors. To gain further insight into the properties of these glycine-gated NMDA receptors, we investigated their current-voltage (I-V dependence. Whole-cell current-voltage relations of glycine currents recorded from NR1/NR3B and NR1/NR3A/NR3B expressing oocytes were found to be linear under our recording conditions. In contrast, NR1/NR3A receptors displayed a strong outwardly rectifying I-V relation. Interestingly, the voltage-dependent inward current block was abolished in the presence of NR1 antagonists, Zn2+ or a combination of both. Further analysis revealed that Ca2+ (1.8 mM present in our recording solutions was responsible for the voltage-dependent inhibition of ion flux through NR1/NR3A receptors. Since physiological concentrations of the divalent cation Mg2+ did not affect the I-V dependence, our data suggest that relief of the voltage-dependent Ca2+ block of NR1/NR3A receptors by Zn2+ may be important for the regulation of excitatory glycinergic transmission, according to the Mg2+-block of conventional NR1/NR2 NMDA receptors.

  19. Coexpression of voltage-dependent calcium channels Cav1.2, 2.1a, and 2.1b in vascular myocytes

    DEFF Research Database (Denmark)

    Andreasen, Ditte; Friis, Ulla Glenert; Uhrenholt, Torben Rene

    2006-01-01

    , and blocking P-type currents (omega-agatoxin IVA 10 nmol/L) led to 20.2+/-3.0% inhibition, whereas 300 nmol/L of omega agatoxin IVA (blocking P/Q-type) inhibited 45.0+/-7.3%. In rat aortic smooth muscle cells (A7r5), blockade of L-type channels resulted in 28.5+/-6.1% inhibition, simultaneous blockade of L...... microscopy revealed expression of both channels in all of the smooth muscle cells. Whole-cell patch clamp on single preglomerular VSMCs from mice showed L-, P-, and Q-type currents. Blockade of the L-type currents by calciseptine (20 nmol/L) inhibited 35.6+/-3.9% of the voltage-dependent Ca2+ current......-type and P-type channels inhibited 58.0+/-11.8%, and simultaneous inhibition of L-, P-, and Q-type channels led to blockade (88.7+/-5.6%) of the Ca2+ current. We conclude that aortic and renal preglomerular smooth muscle cells express L-, P-, and Q-type voltage-dependent Ca2+ channels in the rat and mouse....

  20. Structural mapping of the voltage-dependent sodium channel. Distance between the tetrodotoxin and Centruroides suffusus suffusus II beta-scorpion toxin receptors.

    Science.gov (United States)

    Darbon, H; Angelides, K J

    1984-05-25

    A 7- dimethylaminocoumarin -4-acetate fluorescent derivative of toxin II from the venom of the scorpion Centruroides suffusus suffusus (Css II) has been prepared to study the structural, conformational, and cellular properties of the beta-neurotoxin receptor site on the voltage-dependent sodium channel. The derivative retains high affinity for its receptor site on the synaptosomal sodium channel with a KD of 7 nM and site capacity of 1.5 pmol/mg of synaptosomal protein. The fluorescent toxin is very environmentally sensitive and the fluorescence emission upon binding indicates that the Css II receptor is largely hydrophobic. Binding of tetrodotoxin or batrachotoxin does not alter the spectroscopic properties of bound Css II, whereas toxin V from Leiurus quinquestriatus effects a 10-nm blue shift to a more hydrophobic environment. This is the first direct indication of conformational coupling between these separate neurotoxin receptor sites. The distance between the tetrodotoxin and Css II scorpion toxin receptors on the sodium channel was measured by fluorescence resonance energy transfer. Efficiencies were measured by both donor quenching and acceptor-sensitized emission. The distance between these two neurotoxin sites is about 34 A. The implications of these receptor locations together with other known molecular distances are discussed in terms of a molecular structure of the voltage-dependent sodium channel.

  1. Altered calcium homeostasis in motor neurons following AMPA receptor but not voltage-dependent calcium channels' activation in a genetic model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Guatteo, Ezia; Carunchio, Irene; Pieri, Massimo; Albo, Federica; Canu, Nadia; Mercuri, Nicola B; Zona, Cristina

    2007-10-01

    Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by a substantial loss of motor neurons in the spinal cord, brain stem and motor cortex. By combining electrophysiological recordings with imaging techniques, clearance/buffering capacity of cultured spinal cord motor neurons after a calcium accumulation has been analyzed in response to AMPA receptors' (AMPARs') activation and to depolarizing stimuli in a genetic mouse model of ALS (G93A). Our studies demonstrate that the amplitude of the calcium signal in response to AMPARs' or voltage-dependent calcium channels' activation is not significantly different in controls and G93A motor neurons. On the contrary, in G93A motor neurons, the [Ca(2+)](i) recovery to basal level is significantly slower compared to control neurons following AMPARs but not voltage-dependent calcium channels' activation. This difference was not observed in G93A cultured cortical neurons. This observation is the first to indicate a specific alteration of the calcium clearance linked to AMPA receptors' activation in G93A motor neurons and the involvement of AMPA receptor regulatory proteins controlling both AMPA receptor functionality and the sequence of events connected to them.

  2. Effects of in vitro and in vivo lead exposure on voltage-dependent calcium channels in central neurons of Lymnaea stagnalis.

    Science.gov (United States)

    Audesirk, G

    1987-01-01

    Currents through calcium channels of members of an identified cluster of neurons (B cells) in the pond snail Lymnaea stagnalis were studied under voltage clamp. The normal physiological saline was modified to maximize the visibility of voltage-dependent calcium currents and minimize contamination by other currents. Barium was used as the charge carrier for the calcium channels. Depolarizing voltage steps induce an inward current, the magnitude of which varies with the barium concentration. In brains taken from animals not exposed in vivo to lead, in vitro addition of lead acetate to the recording medium (0.25 to 14 microM) inhibits the barium current by 59 +/- 14% (mean +/- s.d.), in a manner that is independent of the lead concentration. The magnitude of the residual current still varies with the barium concentration. The voltage dependence of the current appears to be unaffected by lead. In contrast to some other calcium-channel blockers, such as cobalt, the inhibition of barium currents by in vitro lead exposure is irreversible, at least in short-term experiments. Contrary to expectations based on these in vitro results, barium currents in B cells of animals exposed to 5 microM lead for 6 to 12 weeks in vivo were approximately twice as large as barium currents in B cells from unexposed controls, when both were recorded in lead-free saline. It is possible that chronic in vivo lead exposure causes an increase in the number of calcium channels in these neurons.

  3. APETx1 from sea anemone Anthopleura elegantissima is a gating modifier peptide toxin of the human ether-a-go-go- related potassium channel.

    Science.gov (United States)

    Zhang, M; Liu, X-S; Diochot, S; Lazdunski, M; Tseng, G-N

    2007-08-01

    We studied the mechanism of action and the binding site of APETx1, a peptide toxin purified from sea anemone, on the human ether-a-go-go-related gene (hERG) channel. Similar to the effects of gating modifier toxins (hanatoxin and SGTx) on the voltage-gated potassium (Kv) 2.1 channel, APETx1 shifts the voltage-dependence of hERG activation in the positive direction and suppresses its current amplitudes elicited by strong depolarizing pulses that maximally activate the channels. The APETx1 binding site is distinctly different from that of a pore-blocking peptide toxin, BeKm-1. Mutations in the S3b region of hERG have dramatic impact on the responsiveness to APETx1: G514C potentiates whereas E518C abolishes the APETx1 effect. Restoring the negative charge at position 518 (methanethiosulfonate ethylsulfonate modification of 518C) partially restores APETx1 responsiveness, supporting an electrostatic interaction between E518 and APETx1. Among the three hERG isoforms, hERG1 and hERG3 are equally responsive to APETx1, whereas hERG2 is insensitive. The key feature seems to be an arginine residue uniquely present at the 514-equivalent position in hERG2, where the other two isoforms possess a glycine. Our data show that APETx1 is a gating modifier toxin of the hERG channel, and its binding site shares characteristics with those of gating modifier toxin binding sites on other Kv channels.

  4. Electrostatic versus Electrochemical Doping and Control of Ferromagnetism in Ion-Gel-Gated Ultrathin La0.5Sr0.5CoO3-δ.

    Science.gov (United States)

    Walter, Jeff; Wang, Helin; Luo, Bing; Frisbie, C Daniel; Leighton, Chris

    2016-08-23

    Recently, electrolyte gating techniques employing ionic liquids/gels in electric double layer transistors have proven remarkably effective in tuning charge carrier density in a variety of materials. The ability to control surface carrier densities at levels above 10(14) cm(-2) has led to widespread use in the study of superconductivity, insulator-metal transitions, etc. In many cases, controversy remains over the doping mechanism, however (i.e., electrostatic vs electrochemical (e.g., redox-based)), and the technique has been less applied to magnetic materials. Here, we discuss ion gel gating of nanoscale 8-unit-cell-thick hole-doped La0.5Sr0.5CoO3-δ (LSCO) films, probing in detail the critical bias windows and doping mechanisms. The LSCO films, which are under compressive stress on LaAlO3(001) substrates, are metallic and ferromagnetic (Curie temperature, TC ∼ 170 K), with strong anomalous Hall effect and perpendicular magnetic anisotropy. Transport measurements reveal that negative gate biases lead to reversible hole accumulation (i.e., predominantly electrostatic operation) up to some threshold, whereas positive bias immediately induces irreversibility. Experiments in inert/O2 atmospheres directly implicate oxygen vacancies in this irreversibility, supported by atomic force microscopy and X-ray photoelectron spectroscopy. The results are thus of general importance, suggesting that hole- and electron-doped oxides may respond very differently to electrolyte gating. Reversible voltage control of electronic/magnetic properties is then demonstrated under hole accumulation, including resistivity, magnetoresistance, and TC. The sizable anomalous Hall coefficient and perpendicular anisotropy in LSCO provide a particularly powerful probe of magnetism, enabling direct extraction of the voltage-dependent order parameter and TC shift. The latter amounts to ∼7%, with potential for much stronger modulation at lower Sr doping.

  5. Frequency and voltage dependence of electric and dielectric properties of Au/TiO2/n-4H-SiC (metal-insulator-semiconductor) type Schottky barrier diodes

    Science.gov (United States)

    Tanrıkulu, E. E.; Yıldız, D. E.; Günen, A.; Altındal, Ş.

    2015-09-01

    The main electrical and dielectric properties of Au/TiO2/n-4H-SiC (MIS) type Schottky barrier diodes (SBDs) have been investigated as functions of frequency and applied bias voltage. We believe that the use of high dielectric interfacial layer between metal and semiconductor can improve the performance of Schottky diodes. From the experimental data, both electrical and dielectric parameters were found as strong function of frequency and applied bias voltage. The Fermi energy level (EF), the concentration of doping donor atoms (P), barrier height (ΦB) and series resistance (Rs) values were obtained from reverse and forward bias C-V characteristics. The changes in EF and ND with frequency are considerably low. Therefore, their values were taken at about constant. The real and imaginary parts of dielectric constant (\\varepsilon \\prime , \\varepsilon \\prime\\prime ), tangent loss (tanδ), ac electrical conductivity (σac), and real and imaginary parts of electric modulus (M‧ and M″) values were also obtained from reverse and forward bias C-V and G/ω-V characteristics. In addition, the voltage dependent profiles of all these electrical and dielectric parameters were drawn for each frequency. These results confirmed that both electrical and dielectric properties of Au/TiO2/n-4H-SiC (MIS) type SBD are quite sensitive to both the frequency and applied bias voltage due to surface polarization, density distribution of interface traps (Dit), and interfacial layer.

  6. Structure of membrane-active toxin from crab spider Heriaeus melloteei suggests parallel evolution of sodium channel gating modifiers in Araneomorphae and Mygalomorphae.

    Science.gov (United States)

    Berkut, Antonina A; Peigneur, Steve; Myshkin, Mikhail Yu; Paramonov, Alexander S; Lyukmanova, Ekaterina N; Arseniev, Alexander S; Grishin, Eugene V; Tytgat, Jan; Shenkarev, Zakhar O; Vassilevski, Alexander A

    2015-01-01

    We present a structural and functional study of a sodium channel activation inhibitor from crab spider venom. Hm-3 is an insecticidal peptide toxin consisting of 35 amino acid residues from the spider Heriaeus melloteei (Thomisidae). We produced Hm-3 recombinantly in Escherichia coli and determined its structure by NMR spectroscopy. Typical for spider toxins, Hm-3 was found to adopt the so-called "inhibitor cystine knot" or "knottin" fold stabilized by three disulfide bonds. Its molecule is amphiphilic with a hydrophobic ridge on the surface enriched in aromatic residues and surrounded by positive charges. Correspondingly, Hm-3 binds to both neutral and negatively charged lipid vesicles. Electrophysiological studies showed that at a concentration of 1 μm Hm-3 effectively inhibited a number of mammalian and insect sodium channels. Importantly, Hm-3 shifted the dependence of channel activation to more positive voltages. Moreover, the inhibition was voltage-dependent, and strong depolarizing prepulses attenuated Hm-3 activity. The toxin is therefore concluded to represent the first sodium channel gating modifier from an araneomorph spider and features a "membrane access" mechanism of action. Its amino acid sequence and position of the hydrophobic cluster are notably different from other known gating modifiers from spider venom, all of which are described from mygalomorph species. We hypothesize parallel evolution of inhibitor cystine knot toxins from Araneomorphae and Mygalomorphae suborders.

  7. Physics-Based Compact Model for CIGS and CdTe Solar Cells: From Voltage-Dependent Carrier Collection to Light-Enhanced Reverse Breakdown: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xingshu; Alam, Muhammad Ashraful; Raguse, John; Garris, Rebekah; Deline, Chris; Silverman, Timothy

    2015-10-15

    In this paper, we develop a physics-based compact model for copper indium gallium diselenide (CIGS) and cadmium telluride (CdTe) heterojunction solar cells that attributes the failure of superposition to voltage-dependent carrier collection in the absorber layer, and interprets light-enhanced reverse breakdown as a consequence of tunneling-assisted Poole-Frenkel conduction. The temperature dependence of the model is validated against both simulation and experimental data for the entire range of bias conditions. The model can be used to characterize device parameters, optimize new designs, and most importantly, predict performance and reliability of solar panels including the effects of self-heating and reverse breakdown due to partial-shading degradation.

  8. Voltage-Dependent Anion Channel 2 of Arabidopsis thaliana (AtVDAC2 Is Involved in ABA-Mediated Early Seedling Development

    Directory of Open Access Journals (Sweden)

    Xufeng Li

    2009-05-01

    Full Text Available The voltage-dependent anion channel (VDAC is the major transport protein in the outer membrane of mitochondria and plays crucial roles in energy metabolism, apoptosis, and metabolites transport. In plants, the expression of VDACs can be affected by different stresses, including drought, salinity and pathogen defense. In this study, we investigated the expression pattern of AtVDAC2 in A. thaliana and found ABA suppressed the accumulation of AtVDAC2 transcripts. Further, phenotype analysis of this VDAC deregulated-expression transgenic Arabidopsis plants indicated that AtVDAC2 anti-sense line showed an ABA-insensitivity phenotype during the early seedling development under ABA treatment. The results suggested that AtVDAC2 might be involved in ABA signaling in A. thaliana.

  9. Involvement of presynaptic voltage-dependent Kv3 channel in endothelin-1-induced inhibition of noradrenaline release from rat gastric sympathetic nerves.

    Science.gov (United States)

    Nakamura, Kumiko; Shimizu, Takahiro; Tanaka, Kenjiro; Taniuchi, Keisuke; Yokotani, Kunihiko

    2012-11-05

    We previously reported that two types of K(+) channels, the BK type Ca(2+)-activated K(+) channel coupled with phospholipase C (PLC) and the voltage-dependent K(+) channel (Kv channel), are, respectively, involved in the prostanoid TP receptor- and muscarinic M(2) receptor-mediated inhibition of noradrenaline (NA) release from rat gastric sympathetic nerves. In the present study, therefore, we examined whether these K(+) channels are involved in endothelin-1-induced inhibition of NA release, using an isolated, vascularly perfused rat stomach. The gastric sympathetic postganglionic nerves around the left gastric artery were electrically stimulated twice at 2.5 Hz for 1 min, and endothelin-1 was added during the second stimulation. Endothelin-1 (1, 2 and 10 nM) dose-dependently inhibited gastric NA release. Endothelin-1 (2 nM)-induced inhibition of NA release was neither attenuated by PLC inhibitors [U-73122 (3 μM) and ET-18-OCH(3) (3 μM)] nor by Ca(2+)-activated K(+) channel blockers [charybdotoxin (0.1 μM) (a blocker of BK type K(+) channel) and apamin (0.3 μM) (a blocker of SK type K(+) channel)]. The endothelin-1-induced inhibitory response was also not attenuated by α-dendrotoxin (0.1 μM) (a selective inhibitor of Kv1 channel), but abolished by 4-aminopyridine (20 μM) (a selectively inhibitory dose for Kv3 channel). These results suggest the involvement of a voltage-dependent Kv3 channel in the endothelin-1-induced inhibition of NA release from the gastric sympathetic nerves in rats.

  10. Ropivacaine-Induced Contraction Is Attenuated by Both Endothelial Nitric Oxide and Voltage-Dependent Potassium Channels in Isolated Rat Aortae

    Directory of Open Access Journals (Sweden)

    Seong-Ho Ok

    2013-01-01

    Full Text Available This study investigated endothelium-derived vasodilators and potassium channels involved in the modulation of ropivacaine-induced contraction. In endothelium-intact rat aortae, ropivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: the nonspecific nitric oxide synthase (NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, the neuronal NOS inhibitor Nω-propyl-L-arginine hydrochloride, the inducible NOS inhibitor 1400W dihydrochloride, the nitric oxide-sensitive guanylyl cyclase (GC inhibitor ODQ, the NOS and GC inhibitor methylene blue, the phosphoinositide-3 kinase inhibitor wortmannin, the cytochrome p450 epoxygenase inhibitor fluconazole, the voltage-dependent potassium channel inhibitor 4-aminopyridine (4-AP, the calcium-activated potassium channel inhibitor tetraethylammonium (TEA, the inward-rectifying potassium channel inhibitor barium chloride, and the ATP-sensitive potassium channel inhibitor glibenclamide. The effect of ropivacaine on endothelial nitric oxide synthase (eNOS phosphorylation in human umbilical vein endothelial cells was examined by western blotting. Ropivacaine-induced contraction was weaker in endothelium-intact aortae than in endothelium-denuded aortae. L-NAME, ODQ, and methylene blue enhanced ropivacaine-induced contraction, whereas wortmannin, Nω-propyl-L-arginine hydrochloride, 1400W dihydrochloride, and fluconazole had no effect. 4-AP and TEA enhanced ropivacaine-induced contraction; however, barium chloride and glibenclamide had no effect. eNOS phosphorylation was induced by ropivacaine. These results suggest that ropivacaine-induced contraction is attenuated primarily by both endothelial nitric oxide and voltage-dependent potassium channels.

  11. Heparin/heparan sulfates bind to and modulate neuronal L-type (Cav1.2) voltage-dependent Ca(2+) channels.

    Science.gov (United States)

    Garau, Gianpiero; Magotti, Paola; Heine, Martin; Korotchenko, Svetlana; Lievens, Patricia Marie-Jeanne; Berezin, Vladimir; Dityatev, Alexander

    2015-12-01

    Our previous studies revealed that L-type voltage-dependent Ca(2+) channels (Cav1.2 L-VDCCs) are modulated by the neural extracellular matrix backbone, polyanionic glycan hyaluronic acid. Here we used isothermal titration calorimetry and screened a set of peptides derived from the extracellular domains of Cav1.2α1 to identify putative binding sites between the channel and hyaluronic acid or another class of polyanionic glycans, such as heparin/heparan sulfates. None of the tested peptides showed detectable interaction with hyaluronic acid, but two peptides derived from the first pore-forming domain of Cav1.2α1 subunit bound to heparin. At 25 °C the binding of the peptide P7 (MGKMHKTCYN) was at ~50 μM, and that of the peptide P8 (GHGRQCQNGTVCKPGWDGPKHG) was at ~21 μM. The Cav1.2α1 first pore forming segment that contained both peptides maintained a high affinity for heparin (~23 μM), integrating their enthalpic and entropic binding contributions. Interaction between heparin and recombinant as well as native full-length neuronal Cav1.2α1 channels was confirmed using the heparin-agarose pull down assay. Whole cell patch clamp recordings in HEK293 cells transfected with neuronal Cav1.2 channels revealed that enzymatic digestion of highly sulfated heparan sulfates with heparinase 1 affects neither voltage-dependence of channel activation nor the level of steady state inactivation, but did speed up channel inactivation. Treatment of hippocampal cultures with heparinase 1 reduced the firing rate and led to appearance of long-lasting bursts in the same manner as treatment with the inhibitor of L-VDCC diltiazem. Thus, heparan sulfate proteoglycans may bind to and regulate L-VDCC inactivation and network activity.

  12. Cyanocobalamin, vitamin B12, depresses glutamate release through inhibition of voltage-dependent Ca2+ influx in rat cerebrocortical nerve terminals (synaptosomes).

    Science.gov (United States)

    Hung, Kun-Long; Wang, Chia-Chuan; Huang, Chia-Yu; Wang, Su-Jane

    2009-01-14

    The effect of cyanocobalamin, vitamin B12, on glutamate release in isolated nerve terminals (synaptosomes) prepared from rat prefrontal cortex was examined. Cyanocobalamin inhibited the release of glutamate evoked by 4-aminopyridine in a concentration-dependent manner. The inhibitory action of cyanocobalamin was blocked by the vesicular transporter inhibitor bafilomycin A1, not by the glutamate transporter inhibitor L-transpyrrolidine-2,4-dicarboxylic acid or the nontransportable glutamate inhibitor DL-threo-beta-benzyloxyaspartate, indicating that this release inhibition results from a reduction of vesicular exocytosis and not from an inhibition of Ca(2+)-independent efflux via glutamate transporter. Examination of the effect of cyanocobalamin on cytosolic free Ca(2+) concentration revealed that the inhibition of glutamate release could be attributed to a reduction in voltage-dependent Ca(2+) influx. Consistent with this, the N- and P/Q-type Ca(2+) channel blocker omega-conotoxin MVIIC, largely attenuated the inhibitory effect of cyanocobalamin on 4-aminopyridine-evoked glutamate release, but the Ca(2+) release inhibitor dantrolene had no effect. Cyanocobalamin did not alter the resting synaptosomal membrane potential or 4-aminopyridine-mediated depolarization; thus, the inhibition of 4-aminopyridine-evoked Ca(2+) influx and glutamate release produced by cyanocobalamin was not due to its decreasing synaptosomal excitability. In addition, cyanocobalamin-mediated inhibition of 4-aminopyridine-evoked Ca(2+) influx and glutamate release was significantly attenuated by protein kinase C inhibitors GF109203X and Ro318220. Furthermore, 4-aminopyridine-induced phosphorylation of protein kinase C was significantly reduced by cyanocobalamin. These results suggest that cyanocobalamin effects a decrease in protein kinase C activation, which subsequently reduces the Ca(2+) entry through voltage-dependent N- and P/Q-type Ca(2+) channels to cause a decrease in evoked glutamate

  13. Effects of acidic pH on voltage-gated ion channels in rat trigeminal mesencephalic nucleus neurons.

    Science.gov (United States)

    Han, Jin-Eon; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon; Jang, Il-Sung

    2017-03-01

    The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent K(+) and Ca(2+) channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent K(+) currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent K(+) currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker Cs(+) (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent Ca(2+) channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions.

  14. Quantum Gates and Circuits

    CERN Document Server

    Di Vincenzo, D P

    1997-01-01

    A historical review is given of the emergence of the idea of the quantum logic gate from the theory of reversible Boolean gates. I highlight the quantum XOR or controlled NOT as the fundamental two-bit gate for quantum computation. This gate plays a central role in networks for quantum error correction.

  15. Intron retention in mRNA encoding ancillary subunit of insect voltage-gated sodium channel modulates channel expression, gating regulation and drug sensitivity.

    Science.gov (United States)

    Bourdin, Céline M; Moignot, Bénédicte; Wang, Lingxin; Murillo, Laurence; Juchaux, Marjorie; Quinchard, Sophie; Lapied, Bruno; Guérineau, Nathalie C; Dong, Ke; Legros, Christian

    2013-01-01

    Insect voltage-gated sodium (Nav) channels are formed by a well-known pore-forming α-subunit encoded by para-like gene and ancillary subunits related to TipE from the mutation "temperature-induced-paralysis locus E." The role of these ancillary subunits in the modulation of biophysical and pharmacological properties of Na(+) currents are not enough documented. The unique neuronal ancillary subunit TipE-homologous protein 1 of Drosophila melanogaster (DmTEH1) strongly enhances the expression of insect Nav channels when heterologously expressed in Xenopus oocytes. Here we report the cloning and functional expression of two neuronal DmTEH1-homologs of the cockroach, Periplaneta americana, PaTEH1A and PaTEH1B, encoded by a single bicistronic gene. In PaTEH1B, the second exon encoding the last 11-amino-acid residues of PaTEH1A is shifted to 3'UTR by the retention of a 96-bp intron-containing coding-message, thus generating a new C-terminal end. We investigated the gating and pharmacological properties of the Drosophila Nav channel variant (DmNav1-1) co-expressed with DmTEH1, PaTEH1A, PaTEH1B or a truncated mutant PaTEH1Δ(270-280) in Xenopus oocytes. PaTEH1B caused a 2.2-fold current density decrease, concomitant with an equivalent α-subunit incorporation decrease in the plasma membrane, compared to PaTEH1A and PaTEH1Δ(270-280). PaTEH1B positively shifted the voltage-dependences of activation and slow inactivation of DmNav1-1 channels to more positive potentials compared to PaTEH1A, suggesting that the C-terminal end of both proteins may influence the function of the voltage-sensor and the pore of Nav channel. Interestingly, our findings showed that the sensitivity of DmNav1-1 channels to lidocaine and to the pyrazoline-type insecticide metabolite DCJW depends on associated TEH1-like subunits. In conclusion, our work demonstrates for the first time that density, gating and pharmacological properties of Nav channels expressed in Xenopus oocytes can be modulated by an

  16. Edge-on gating effect in molecular wires.

    Science.gov (United States)

    Lo, Wai-Yip; Bi, Wuguo; Li, Lianwei; Jung, In Hwan; Yu, Luping

    2015-02-11

    This work demonstrates edge-on chemical gating effect in molecular wires utilizing the pyridinoparacyclophane (PC) moiety as the gate. Different substituents with varied electronic demands are attached to the gate to simulate the effect of varying gating voltages similar to that in field-effect transistor (FET). It was observed that the orbital energy level and charge carrier's tunneling barriers can be tuned by changing the gating group from strong electron acceptors to strong electron donors. The single molecule conductance and current-voltage characteristics of this molecular system are truly similar to those expected for an actual single molecular transistor.

  17. Graded tunnelling barrier and oxygen concentration in thermally grown ultrathin SiO{sub x} gate oxide

    Energy Technology Data Exchange (ETDEWEB)

    Gitlin, Daniel [Device Physics Laboratory, Xilinx, Inc., 2100 Logic Drive, San Jose, CA 95124-3400 (United States); Karp, James [Device Physics Laboratory, Xilinx, Inc., 2100 Logic Drive, San Jose, CA 95124-3400 (United States); Moyzhes, Boris [Geballe Laboratory for Advanced Materials, McCullough Building, Stanford University, CA 94305-4045 (United States)

    2007-04-07

    Barrier parameters of a thermally grown SiO{sub x} gate oxide are derived by relating the SIMS oxygen concentration profile to the barrier height. Even in the simple analytical form such a graded barrier model agrees with the tunnelling current and its voltage dependence in both directions. Asymmetrical tunnelling I-Vs in the symmetrical n{sup +}Si-SiO{sub x}-n{sup +}Si structure are due to both graded barrier and penetration of carriers into the gate oxide at the SiO{sub x}-Si substrate interface.

  18. A CACNA1C variant associated with reduced voltage-dependent inactivation, increased CaV1.2 channel window current, and arrhythmogenesis.

    Directory of Open Access Journals (Sweden)

    Jessica A Hennessey

    Full Text Available Mutations in CACNA1C that increase current through the CaV1.2 L-type Ca2+ channel underlie rare forms of long QT syndrome (LQTS, and Timothy syndrome (TS. We identified a variant in CACNA1C in a male child of Filipino descent with arrhythmias and extracardiac features by candidate gene sequencing and performed functional expression studies to electrophysiologically characterize the effects of the variant on CaV1.2 channels. As a baby, the subject developed seizures and displayed developmental delays at 30 months of age. At age 5 years, he displayed a QTc of 520 ms and experienced recurrent VT. Physical exam at 17 years of age was notable for microcephaly, short stature, lower extremity weakness and atrophy with hyperreflexia, spastic diplegia, multiple dental caries and episodes of rhabdomyolysis. Candidate gene sequencing identified a G>C transversion at position 5731 of CACNA1C (rs374528680 predicting a glycine>arginine substitution at residue 1911 (p.G1911R of CaV1.2. The allele frequency of this variant is 0.01 in Malays, but absent in 984 Caucasian alleles and in the 1000 genomes project. In electrophysiological analyses, the variant decreased voltage-dependent inactivation, thus causing a gain of function of CaV1.2. We also observed a negative shift of V1/2 of activation and positive shift of V1/2 of channel inactivation, resulting in an increase of the window current. Together, these suggest a gain-of-function effect on CaV1.2 and suggest increased susceptibility for arrhythmias in certain clinical settings. The p.G1911R variant was also identified in a case of sudden unexplained infant death (SUID, for which an increasing number of clinical observations have demonstrated can be associated with arrhythmogenic mutations in cardiac ion channels. In summary, the combined effects of the CACNA1C variant to diminish voltage-dependent inactivation of CaV1.2 and increase window current expand our appreciation of mechanisms by which a gain of

  19. Involvement of inositol 1,4,5-trisphosphate formation in the voltage-dependent regulation of the Ca(2+) concentration in porcine coronary arterial smooth muscle cells.

    Science.gov (United States)

    Yamamura, Hisao; Ohya, Susumu; Muraki, Katsuhiko; Imaizumi, Yuji

    2012-08-01

    The involvement of inositol 1,4,5-trisphosphate (IP(3)) formation in the voltage-dependent regulation of intracellular Ca(2+) concentration ([Ca(2+)](i)) was examined in smooth muscle cells of the porcine coronary artery. Slow ramp depolarization from -90 to 0 mV induced progressive [Ca(2+)](i) increase. The slope was reduced or increased in the presence of Cd(2+) or (±)-1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-[trifluoromethyl]-phenyl)pyridine-3-carboxlic acid methyl ester (Bay K 8644), respectively. The decrease in [Ca(2+)](i) via the membrane hyperpolarization induced by K(+) channel openers (levcromakalim and Evans blue) under current clamp was identical to that under voltage clamp. The step hyperpolarization from -40 to -80 mV reduced [Ca(2+)](i) uniformly over the whole-cell area with a time constant of ∼10 s. The [Ca(2+)](i) at either potential was unaffected by heparin, an inhibitor of IP(3) receptors. Alternatively, [Ca(2+)](i) rapidly increased in the peripheral regions by depolarization from -80 to 0 mV and stayed at that level (∼400 nM) during a 60-s pulse. When the pipette solution contained IP(3) pathway blockers [heparin, 2-aminoethoxydiphenylborate, xestospongin C, or 1-[6-[((17β)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U73122)], the peak [Ca(2+)](i) was unchanged, but the sustained [Ca(2+)](i) was gradually reduced by ∼250 nM within 30 s. In the presence of Cd(2+), a long depolarization period slightly increased the [Ca(2+)](i), which was lower than that in the presence of heparin alone. In coronary arterial myocytes, the sustained increase in the [Ca(2+)](i) during depolarization was partly caused by the Ca(2+) release mediated by the enhanced formation of IP(3). The initial [Ca(2+)](i) elevation triggered by the Ca(2+) influx though voltage-dependent Ca(2+) channels may be predominantly responsible for the activation of phospholipase C for IP(3) formation.

  20. A Microscopic Capacitor Model of Voltage Coupling in Membrane Proteins: Gating Charge Fluctuations in Ci-VSD.

    Science.gov (United States)

    Kim, Ilsoo; Warshel, Arieh

    2016-01-28

    The voltage sensitivity of membrane proteins is reflected in the response of the voltage sensing domains (VSDs) to the changes in membrane potential. This response is implicated in the displacement of positively charged residues, associated with the conformational changes of VSDs. The displaced charges generate nonlinear (i.e., voltage-dependent) capacitance current called the gating current (and its corresponding gating charge), which is a key experimental quantity that characterizes voltage activation in VSMP. However, the relevant theoretical/computational approaches, aimed to correlate the structural information on VSMP to electrophysiological measurements, have been rather limited, posing a broad challenge in computer simulations of VSMP. Concomitant with the development of our coarse-graining (CG) model of voltage coupling, we apply our theoretical framework for the treatments of voltage effects in membrane proteins to modeling the VSMP activation, taking the VSDs (Ci-VSD) derived from the Ciona intestinalis voltage sensitive phosphatase (Ci-VSP) as a model system. Our CG model reproduces the observed gating charge of Ci-VSD activation in several different perspectives. In particular, a new closed-form expression of the gating charge is evaluated in both nonequilibrium and equilibrium ways, while considering the fluctuation-dissipation relation that connects a nonequilibrium measurement of the gating charge to an equilibrium measurement of charge fluctuations (i.e., the voltage-independent linear component of membrane capacitance). In turn, the expression uncovers a novel link that connects an equilibrium measurement of the voltage-independent linear capacitance to a nonequilibrium measurement of the voltage-dependent nonlinear capacitance (whose integral over voltage is equal to the gating charge). In addition, our CG model yields capacitor-like voltage dependent free energy parabolas, resulting in the free energy difference and the free energy barrier for

  1. Frequency response of electrolyte-gated graphene electrodes and transistors

    Science.gov (United States)

    Drieschner, Simon; Guimerà, Anton; Cortadella, Ramon G.; Viana, Damià; Makrygiannis, Evangelos; Blaschke, Benno M.; Vieten, Josua; Garrido, Jose A.

    2017-03-01

    The interface between graphene and aqueous electrolytes is of high importance for applications of graphene in the field of biosensors and bioelectronics. The graphene/electrolyte interface is governed by the low density of states of graphene that limits the capacitance near the Dirac point in graphene and the sheet resistance. While several reports have focused on studying the capacitance of graphene as a function of the gate voltage, the frequency response of graphene electrodes and electrolyte-gated transistors has not been discussed so far. Here, we report on the impedance characterization of single layer graphene electrodes and transistors, showing that due to the relatively high sheet resistance of graphene, the frequency response is governed by the distribution of resistive and capacitive circuit elements along the graphene/electrolyte interface. Based on an analytical solution for the impedance of the distributed circuit elements, we model the graphene/electrolyte interface both for the electrode and the transistor configurations. Using this model, we can extract the relevant material and device parameters such as the voltage-dependent intrinsic sheet and series resistances as well as the interfacial capacitance. The model also provides information about the frequency threshold of electrolyte-gated graphene transistors, above which the device exhibits a non-resistive response, offering an important insight into the suitable frequency range of operation of electrolyte-gated graphene devices.

  2. Forgetting of long-term memory requires activation of NMDA receptors, L-type voltage-dependent Ca2+ channels, and calcineurin

    Science.gov (United States)

    Sachser, Ricardo Marcelo; Santana, Fabiana; Crestani, Ana Paula; Lunardi, Paula; Pedraza, Lizeth Katherine; Quillfeldt, Jorge Alberto; Hardt, Oliver; de Oliveira Alvares, Lucas

    2016-01-01

    In the past decades, the cellular and molecular mechanisms underlying memory consolidation, reconsolidation, and extinction have been well characterized. However, the neurobiological underpinnings of forgetting processes remain to be elucidated. Here we used behavioral, pharmacological and electrophysiological approaches to explore mechanisms controlling forgetting. We found that post-acquisition chronic inhibition of the N-methyl-D-aspartate receptor (NMDAR), L-type voltage-dependent Ca2+ channel (LVDCC), and protein phosphatase calcineurin (CaN), maintains long-term object location memory that otherwise would have been forgotten. We further show that NMDAR activation is necessary to induce forgetting of object recognition memory. Studying the role of NMDAR activation in the decay of the early phase of long-term potentiation (E-LTP) in the hippocampus, we found that ifenprodil infused 30 min after LTP induction in vivo blocks the decay of CA1-evoked postsynaptic plasticity, suggesting that GluN2B-containing NMDARs activation are critical to promote LTP decay. Taken together, these findings indicate that a well-regulated forgetting process, initiated by Ca2+ influx through LVDCCs and GluN2B-NMDARs followed by CaN activation, controls the maintenance of hippocampal LTP and long-term memories over time. PMID:26947131

  3. Evidence for functional interaction of plasma membrane electron transport, voltage-dependent anion channel and volume-regulated anion channel in frog aorta

    Indian Academy of Sciences (India)

    Rashmi P Rao; J Prakasa Rao

    2010-12-01

    Frog aortic tissue exhibits plasma membrane electron transport (PMET) owing to its ability to reduce ferricyanide even in the presence of mitochondrial poisons, such as cyanide and azide. Exposure to hypotonic solution (108 mOsmol/kg H2O) enhanced the reduction of ferricyanide in excised aortic tissue of frog. Increment in ferricyanide reductase activity was also brought about by the presence of homocysteine (100 M dissolved in isotonic frog Ringer solution), a redox active compound and a potent modulator of PMET. Two plasma-membrane-bound channels, the volume regulated anion channel (VRAC) and the voltage-dependent anion channel (VDAC), are involved in the response to hypotonic stress. The presence of VRAC and VDAC antagonists–tamoxifen, glibenclamide, fluoxetine and verapamil, and 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS), respectively–inhibited this enhanced activity brought about by either hypotonic stress or homocysteine. The blockers do not affect the ferricyanide reductase activity under isotonic conditions. Taken together, these findings indicate a functional interaction of the three plasma membrane proteins, namely, ferricyanide reductase (PMET), VDAC and VRAC.

  4. Correlation between Barrier Width, Barrier Height, and DC Bias Voltage Dependences on the Magnetoresistance Ratio in Ir-Mn Exchange Biased Single and Double Tunnel Junctions

    Science.gov (United States)

    Saito, Yoshiaki; Amano, Minoru; Nakajima, Kentaro; Takahashi, Shigeki; Sagoi, Masayuki; Inomata, Koichiro

    2000-10-01

    Dual spin-valve-type double tunnel junctions (DTJs) of Ir-Mn/CoFe/AlOx/Co90Fe10/AlOx/CoFe/Ir-Mn and spin-valve-type single tunnel junctions (STJs) of Ir-Mn/CoFe/AlOx/CoFe/Ni-Fe were fabricated using an ultrahigh vacuum sputtering system, conventional photolithography and ion-beam milling. The STJs could be fabricated with various barrier heights by changing the oxidization conditions during deposition and changing the annealing temperature after deposition, while the AlOx layer thickness remained unchanged. There was a correlation between barrier width, height estimated using Simmons’ expressions, and dc bias voltage dependence on the MR ratio. The VB dependence on the tunneling magnetoresistance (TMR) ratio was mainly related to the barrier width, and the decrease in the TMR ratio with increasing bias voltage is well explained, taking into account the spin-independent two-step tunneling via defect states in the barrier, as a main mechanism, at room temperature. Under optimized oxidization and annealing conditions, the maximum TMR ratio at a low bias voltage, and the dc bias voltage value at which the TMR ratio decreases in value by half (V1/2) were 42.4% and 952 mV in DTJs, and 49.0% and 425 mV in STJs, respectively.

  5. Flow- and voltage-dependent blocking effect of ethosuximide on the inward rectifier K⁺ (Kir2.1) channel.

    Science.gov (United States)

    Huang, Chiung-Wei; Kuo, Chung-Chin

    2015-08-01

    Absence seizures are manifestations of abnormal thalamocortical oscillations characterized by spike-and-wave complexes in EEG. Ethosuximide (ETX) is one of the principal medications against absence seizures. We investigate the effect of ETX on the Kir2.1 channel, a prototypical inward rectifier K(+) channel possibly playing an important role in the setting of neuronal membrane potential. We demonstrate that the outward currents of Kir2.1 channels are significantly inhibited by intracellular ETX. We further show that the movement of neutral molecule ETX in the Kir2.1 channel is accompanied by ∼1.2 K(+), giving rise to the vivid voltage dependence of ETX unbinding rate. Moreover, the apparent affinity (K d ) of ETX in the channels are decreased by single-point mutations involving M183, E224, and S165, and especially by double mutations involving T141/S165, which always also disrupt the flux-coupling feature of ETX block. Molecular dynamics simulation demonstrates narrowing of the pore at ∼D172 by binding of ETX to S165 or T141. ETX block of the Kir2.1 channels may cause a modest but critical depolarization of the relevant neurons, decreasing available T-type Ca(2+) channels and consequently lessening pathological thalamocortical burst discharges.

  6. Forgetting of long-term memory requires activation of NMDA receptors, L-type voltage-dependent Ca2+ channels, and calcineurin.

    Science.gov (United States)

    Sachser, Ricardo Marcelo; Santana, Fabiana; Crestani, Ana Paula; Lunardi, Paula; Pedraza, Lizeth Katherine; Quillfeldt, Jorge Alberto; Hardt, Oliver; Alvares, Lucas de Oliveira

    2016-03-07

    In the past decades, the cellular and molecular mechanisms underlying memory consolidation, reconsolidation, and extinction have been well characterized. However, the neurobiological underpinnings of forgetting processes remain to be elucidated. Here we used behavioral, pharmacological and electrophysiological approaches to explore mechanisms controlling forgetting. We found that post-acquisition chronic inhibition of the N-methyl-D-aspartate receptor (NMDAR), L-type voltage-dependent Ca(2+) channel (LVDCC), and protein phosphatase calcineurin (CaN), maintains long-term object location memory that otherwise would have been forgotten. We further show that NMDAR activation is necessary to induce forgetting of object recognition memory. Studying the role of NMDAR activation in the decay of the early phase of long-term potentiation (E-LTP) in the hippocampus, we found that ifenprodil infused 30 min after LTP induction in vivo blocks the decay of CA1-evoked postsynaptic plasticity, suggesting that GluN2B-containing NMDARs activation are critical to promote LTP decay. Taken together, these findings indicate that a well-regulated forgetting process, initiated by Ca(2+) influx through LVDCCs and GluN2B-NMDARs followed by CaN activation, controls the maintenance of hippocampal LTP and long-term memories over time.

  7. Differential rescue of spatial memory deficits in aged rats by L-type voltage-dependent calcium channel and ryanodine receptor antagonism.

    Science.gov (United States)

    Hopp, S C; D'Angelo, H M; Royer, S E; Kaercher, R M; Adzovic, L; Wenk, G L

    2014-11-01

    Age-associated memory impairments may result as a consequence of neuroinflammatory induction of intracellular calcium (Ca(+2)) dysregulation. Altered L-type voltage-dependent calcium channel (L-VDCC) and ryanodine receptor (RyR) activity may underlie age-associated learning and memory impairments. Various neuroinflammatory markers are associated with increased activity of both L-VDCCs and RyRs, and increased neuroinflammation is associated with normal aging. In vitro, pharmacological blockade of L-VDCCs and RyRs has been shown to be anti-inflammatory. Here, we examined whether pharmacological blockade of L-VDCCs or RyRs with the drugs nimodipine and dantrolene, respectively, could improve spatial memory and reduce age-associated increases in microglia activation. Dantrolene and nimodipine differentially attenuated age-associated spatial memory deficits but were not anti-inflammatory in vivo. Furthermore, RyR gene expression was inversely correlated with spatial memory, highlighting the central role of Ca(+2) dysregulation in age-associated memory deficits.

  8. α-Synuclein Shows High Affinity Interaction with Voltage-dependent Anion Channel, Suggesting Mechanisms of Mitochondrial Regulation and Toxicity in Parkinson Disease.

    Science.gov (United States)

    Rostovtseva, Tatiana K; Gurnev, Philip A; Protchenko, Olga; Hoogerheide, David P; Yap, Thai Leong; Philpott, Caroline C; Lee, Jennifer C; Bezrukov, Sergey M

    2015-07-24

    Participation of the small, intrinsically disordered protein α-synuclein (α-syn) in Parkinson disease (PD) pathogenesis has been well documented. Although recent research demonstrates the involvement of α-syn in mitochondrial dysfunction in neurodegeneration and suggests direct interaction of α-syn with mitochondria, the molecular mechanism(s) of α-syn toxicity and its effect on neuronal mitochondria remain vague. Here we report that at nanomolar concentrations, α-syn reversibly blocks the voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane that controls most of the metabolite fluxes in and out of the mitochondria. Detailed analysis of the blockage kinetics of VDAC reconstituted into planar lipid membranes suggests that α-syn is able to translocate through the channel and thus target complexes of the mitochondrial respiratory chain in the inner mitochondrial membrane. Supporting our in vitro experiments, a yeast model of PD shows that α-syn toxicity in yeast depends on VDAC. The functional interactions between VDAC and α-syn, revealed by the present study, point toward the long sought after physiological and pathophysiological roles for monomeric α-syn in PD and in other α-synucleinopathies.

  9. New gate opening hours

    CERN Multimedia

    GS Department

    2009-01-01

    Please note the new opening hours of the gates as well as the intersites tunnel from the 19 May 2009: GATE A 7h - 19h GATE B 24h/24 GATE C 7h - 9h\t17h - 19h GATE D 8h - 12h\t13h - 16h GATE E 7h - 9h\t17h - 19h Prévessin 24h/24 The intersites tunnel will be opened from 7h30 to 18h non stop. GS-SEM Group Infrastructure and General Services Department

  10. Ion permeation and block of the gating pore in the voltage sensor of NaV1.4 channels with hypokalemic periodic paralysis mutations.

    Science.gov (United States)

    Sokolov, Stanislav; Scheuer, Todd; Catterall, William A

    2010-08-01

    Hypokalemic periodic paralysis and normokalemic periodic paralysis are caused by mutations of the gating charge-carrying arginine residues in skeletal muscle Na(V)1.4 channels, which induce gating pore current through the mutant voltage sensor domains. Inward sodium currents through the gating pore of mutant R666G are only approximately 1% of central pore current, but substitution of guanidine for sodium in the extracellular solution increases their size by 13- +/- 2-fold. Ethylguanidine is permeant through the R666G gating pore at physiological membrane potentials but blocks the gating pore at hyperpolarized potentials. Guanidine is also highly permeant through the proton-selective gating pore formed by the mutant R666H. Gating pore current conducted by the R666G mutant is blocked by divalent cations such as Ba(2+) and Zn(2+) in a voltage-dependent manner. The affinity for voltage-dependent block of gating pore current by Ba(2+) and Zn(2+) is increased at more negative holding potentials. The apparent dissociation constant (K(d)) values for Zn(2+) block for test pulses to -160 mV are 650 +/- 150 microM, 360 +/- 70 microM, and 95.6 +/- 11 microM at holding potentials of 0 mV, -80 mV, and -120 mV, respectively. Gating pore current is blocked by trivalent cations, but in a nearly voltage-independent manner, with an apparent K(d) for Gd(3+) of 238 +/- 14 microM at -80 mV. To test whether these periodic paralyses might be treated by blocking gating pore current, we screened several aromatic and aliphatic guanidine derivatives and found that 1-(2,4-xylyl)guanidinium can block gating pore current in the millimolar concentration range without affecting normal Na(V)1.4 channel function. Together, our results demonstrate unique permeability of guanidine through Na(V)1.4 gating pores, define voltage-dependent and voltage-independent block by divalent and trivalent cations, respectively, and provide initial support for the concept that guanidine-based gating pore blockers

  11. Frequency and voltage dependence dielectric properties, ac electrical conductivity and electric modulus profiles in Al/Co{sub 3}O{sub 4}-PVA/p-Si structures

    Energy Technology Data Exchange (ETDEWEB)

    Bilkan, Çiğdem, E-mail: cigdembilkan@gmail.com [Department of Physics, Faculty of Sciences, The University of Çankırı Karatekin, 18100 Çankırı (Turkey); Azizian-Kalandaragh, Yashar [Department of Physics, Faculty of Science, The University of Mohaghegh Ardabili, Ardabil (Iran, Islamic Republic of); Altındal, Şemsettin [Department of Physics, Faculty of Sciences, The University of Gazi, 06500 Ankara (Turkey); Shokrani-Havigh, Roya [Department of Physics, Faculty of Science, The University of Mohaghegh Ardabili, Ardabil (Iran, Islamic Republic of)

    2016-11-01

    In this research a simple microwave-assisted method have been used for preparation of cobalt oxide nanostructures. The as-prepared sample has been investigated by UV–vis spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM). On the other hand, frequency and voltage dependence of both the real and imaginary parts of dielectric constants (ε′, ε″) and electric modulus (M′ and M″), loss tangent (tanδ), and ac electrical conductivity (σ{sub ac}) values of Al/Co{sub 3}O{sub 4}-PVA/p-Si structures were obtained in the wide range of frequency and voltage using capacitance (C) and conductance (G/ω) data at room temperature. The values of ε′, ε″ and tanδ were found to decrease with increasing frequency almost for each applied bias voltage, but the changes in these parameters become more effective in the depletion region at low frequencies due to the charges at surface states and their relaxation time and polarization effect. While the value of σ is almost constant at low frequency, increases almost as exponentially at high frequency which are corresponding to σ{sub dc} and σ{sub ac}, respectively. The M′ and M″ have low values at low frequencies region and then an increase with frequency due to short-range mobility of charge carriers. While the value of M′ increase with increasing frequency, the value of M″ shows two peak and the peaks positions shifts to higher frequency with increasing applied voltage due to the decrease of the polarization and N{sub ss} effects with increasing frequency.

  12. Alterations of voltage-dependent calcium channel currents in basilar artery smooth muscle cells at early stage of subarachnoid hemorrhage in a rabbit model.

    Directory of Open Access Journals (Sweden)

    Xianqing Shi

    Full Text Available OBJECTIVE: To investigate the changes in the currents of voltage-dependent calcium channels (VDCCs in smooth muscle cells of basilar artery in a rabbit model of subarachnoid hemorrhage (SAH. METHODS: New Zealand white rabbits were randomly divided into five groups: sham (C, normal (N, 24 hours (S1, 48 hours (S2 and 72 hours (S3 after SAH. Non-heparinized autologous arterial blood (1 ml/kg was injected into the cisterna magna to create SAH after intravenous anesthesia, and 1 ml/kg of saline was injected into cisterna magna in the sham group. Rabbits in group N received no injections. Basilar artery in S1, S2, S3 group were isolated at 24, 48, 72 hours after SAH. Basilar artery in group C was isolated at 72 hours after physiological saline injection. Basilar artery smooth muscle cells were isolated for all groups. Whole-cell patch-clamp technique was utilized to record cell membrane capacitance and VDCCs currents. The VDCCs antagonist nifedipine was added to the bath solution to block the Ca(++ channels currents. RESULTS: There were no significant differences in the number of cells isolated, the cell size and membrane capacitance among all the five groups. VDCC currents in the S1-S3 groups had higher amplitudes than those in control and sham groups. The significant change of current amplitude was observed at 72 hours after SAH, which was higher than those of 24 and 48 hours. The VDCCs were shown to expression in human artery smooth muscle cells. CONCLUSIONS: The changes of activation characteristics and voltage-current relationship at 72 hours after SAH might be an important event which leads to a series of molecular events in the microenvironment of the basilar artery smooth muscle cells. This may be the key time point for potential therapeutic intervention against subarachnoid hemorrhage.

  13. Delta receptors are required for full inhibitory coupling of mu-receptors to voltage-dependent Ca(2+) channels in dorsal root ganglion neurons.

    Science.gov (United States)

    Walwyn, Wendy; John, Scott; Maga, Matthew; Evans, Christopher J; Hales, Tim G

    2009-07-01

    Recombinant micro and delta opioid receptors expressed in cell lines can form heterodimers with distinctive properties and trafficking. However, a role for opioid receptor heterodimerization in neurons has yet to be identified. The inhibitory coupling of opioid receptors to voltage-dependent Ca(2+) channels (VDCCs) is a relatively inefficient process and therefore provides a sensitive assay of altered opioid receptor function and expression. We examined micro-receptor coupling to VDCCs in dorsal root ganglion neurons of delta(+/+), delta(+/-), and delta(-/-) mice. Neurons deficient in delta receptors exhibited reduced inhibition of VDCCs by morphine and [D-Ala(2),Phe(4),Gly(5)-ol]-enkephalin (DAMGO). An absence of delta receptors caused reduced efficacy of DAMGO without affecting potency. An absence of delta receptors reduced neither the density of VDCCs nor their inhibition by either the GABA(B) receptor agonist baclofen or intracellular guanosine 5'-O-(3-thio)triphosphate. Flow cytometry revealed a reduction in micro-receptor surface expression in delta(-/-) neurons without altered DAMGO-induced internalization. There was no change in micro-receptor mRNA levels. D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)-sensitive mu-receptor-coupling efficacy was fully restored to delta(+/+) levels in delta(-/-) neurons by expression of recombinant delta receptors. However, the dimerization-deficient delta-15 construct expressed in delta(-/-) neurons failed to fully restore the inhibitory coupling of micro-receptors compared with that seen in delta(+/+) neurons, suggesting that, although not essential for micro-receptor function, micro-delta receptor dimerization contributes to full micro-agonist efficacy. Because DAMGO exhibited a similar potency in delta(+/+) and delta(-/-) neurons and caused similar levels of internalization, the role for heterodimerization is probably at the level of receptor biosynthesis.

  14. 线粒体电压依赖性阴离子通道与心血管疾病%Voltage-dependent Anion Channel and Cardiovascular Diseases

    Institute of Scientific and Technical Information of China (English)

    夏晶

    2013-01-01

    电压依赖性阴离子通道(VDAC)是位于线粒体外膜的通道蛋白,是线粒体与细胞质之间转运ATP以及其他代谢产物的主要通道,在线粒体代谢和细胞生长中发挥重要调控作用.近期研究发现,在心肌缺血再灌、糖尿病、心衰、高血压和动脉粥样硬化时,VDAC表达明显增加,引起细胞内钙离子循环紊乱、氧化应激,进而导致细胞凋亡,已成为心血管疾病研究的新热点.本文就VDAC的分子功能,调控及其在心血管疾病中的作用和相关机制进行综述.%The voltage-dependent anion channel (VDAC),a mitochondrial membrane channel protein located in the outer of mitochondrial membrane,is the main pathway between mitochondria and cytoplasm exchanging ADP,ATP,and other metabolites,and plays an important role in mitochondrial metabolism and cell growth.A growing evidence showed that VDAC was increased in cardiovascular diseases including myocardial ischemia and reperfusion,diabetes,heart failure,hypertension and atherosclerosis.The abnormal state of VDAC will result in cell death by inducing calcium cycling dysfunction and oxidative stress.And VDAC has become a hot topic in the field of cardiovascular diseases research.In this article,we will introduce the molecular function and regulation of VDAC and its role in cardiovascular diseases.

  15. IgG anti-GalNAc-GD1a antibody inhibits the voltage-dependent calcium channel currents in PC12 pheochromocytoma cells.

    Science.gov (United States)

    Nakatani, Yoshihiko; Nagaoka, Takumi; Hotta, Sayako; Utsunomiya, Iku; Yoshino, Hiide; Miyatake, Tadashi; Hoshi, Keiko; Taguchi, Kyoji

    2007-03-01

    We investigated the effects of IgG anti-GalNAc-GD1a antibodies, produced by immunizing rabbits with GalNAc-GD1a, on the voltage-dependent calcium channel (VDCCs) currents in nerve growth factor (NGF)-differentiated PC12 pheochromocytoma cells. VDCCs currents in NGF-differentiated PC12 cells were recorded using the whole-cell patch-clamp technique. Immunized rabbit serum that had a high titer of anti-GalNAc-GD1a antibodies inhibited the VDCCs currents in the NGF-differentiated PC12 cells (36.0+/-9.6% reduction). The inhibitory effect of this serum was reversed to some degree within 3-4 min by washing with bath solution. Similarly, application of purified IgG from rabbit serum immunized with GalNAc-GD1a significantly inhibited the VDCCs currents in PC12 cells (30.6+/-2.5% reduction), and this inhibition was recovered by washing with bath solution. Furthermore, the inhibitory effect was also observed in the GalNAc-GD1a affinity column binding fraction (reduction of 31.1+/-9.85%), while the GalNAc-GD1a affinity column pass-through fraction attenuated the inhibitory effect on VDCCs currents. Normal rabbit serum and normal rabbit IgG did not affect the VDCCs currents in the PC12 cells. In an immunocytochemical study using fluorescence staining, the PC12 cells were stained using GalNAc-GD1a binding fraction. These results indicate that anti-GalNAc-GD1a antibodies inhibit the VDCCs currents in NGF-differentiated PC12 cells.

  16. Voltage-dependent anion channels (VDACs) promote mitophagy to protect neuron from death in an early brain injury following a subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Li, Jian; Lu, Jianfei; Mi, Yongjie; Shi, Zhao; Chen, Chunhua; Riley, John; Zhou, Changman

    2014-07-21

    The term mitophagy is coined to describe the selective removal of mitochondria by autophagy but the process itself is still contentious, especially in the early period following subarachnoid hemorrhage (SAH). In the present study, we investigated the role of mitophagy following 48h after SAH injury in rats. Specifically evaluating whether mitophagy, through voltage dependant anion channels (VDACs) interacting with microtubule-associated protein 1 light chain 3, could orchestrate the induction of apoptotic and necrotic cell death in neurons, a VDAC1siRNA and an activitor Rapamycian (RAPA), were engaged. One hundred and twelve male Sprague-Dawley rats were randomly divided into 4 groups: Sham, SAH, SAH+VDAC1siRNA, and SAH+RAPA. Outcomes measured included mortality rate, brain edema, BBB disruption, and neurobehavioral testing. We also used western blotting techniques to analyze the expressions of key mitophagic/autophagic proteins and pro-apoptotic protein such as ROS, VDAC1, LC-3II and Caspase-3. Rapamycin treatment significantly improved the mortality rate, cerebral edema, and neurobehavioral deficits; apoptotic and necrotic cell death in neurons were reduced by Rapamycin following SAH injury. However, VDAC1siRNA worsened the brain injury following SAH. Immunohistochemical staining and western blot analysis demonstrated a decreased expression of VDAC1, LC3II, and an increase of ROS and Caspase-3 followed by VDAC1siRNA administration. In conclusion, mitophagy induced by VDAC1 following SAH injury may in fact play a significant role in neuroprotection, the mechanism which may be through the attenuation of the apoptosic and necrosic molecular pathways. This translates a preservation of functional integrity and an improvement in mortality.

  17. Frequency and voltage dependence dielectric properties, ac electrical conductivity and electric modulus profiles in Al/Co3O4-PVA/p-Si structures

    Science.gov (United States)

    Bilkan, Çiğdem; Azizian-Kalandaragh, Yashar; Altındal, Şemsettin; Shokrani-Havigh, Roya

    2016-11-01

    In this research a simple microwave-assisted method have been used for preparation of cobalt oxide nanostructures. The as-prepared sample has been investigated by UV-vis spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM). On the other hand, frequency and voltage dependence of both the real and imaginary parts of dielectric constants (ε‧, ε″) and electric modulus (M‧ and M″), loss tangent (tanδ), and ac electrical conductivity (σac) values of Al/Co3O4-PVA/p-Si structures were obtained in the wide range of frequency and voltage using capacitance (C) and conductance (G/ω) data at room temperature. The values of ε‧, ε″ and tanδ were found to decrease with increasing frequency almost for each applied bias voltage, but the changes in these parameters become more effective in the depletion region at low frequencies due to the charges at surface states and their relaxation time and polarization effect. While the value of σ is almost constant at low frequency, increases almost as exponentially at high frequency which are corresponding to σdc and σac, respectively. The M‧ and M″ have low values at low frequencies region and then an increase with frequency due to short-range mobility of charge carriers. While the value of M‧ increase with increasing frequency, the value of M″ shows two peak and the peaks positions shifts to higher frequency with increasing applied voltage due to the decrease of the polarization and Nss effects with increasing frequency.

  18. The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K{sup +} channels in rabbit coronary arterial smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hongliang; Hong, Da Hye; Kim, Han Sol; Kim, Hye Won [Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701 (Korea, Republic of); Jung, Won-Kyo [Department of Biomedical Engineering, Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 608-737 (Korea, Republic of); Na, Sung Hun [Institute of Medical Sciences, Department of Obstetrics and Gynecology, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, 200-701 (Korea, Republic of); Jung, In Duk; Park, Yeong-Min [Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701 (Korea, Republic of); Choi, Il-Whan, E-mail: cihima@inje.ac.kr [Department of Microbiology, Inje University College of Medicine, Busan, 614-735 (Korea, Republic of); Park, Won Sun, E-mail: parkws@kangwon.ac.kr [Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701 (Korea, Republic of)

    2015-06-15

    We investigated the effects of the calmodulin inhibitor CGS 9343B on voltage-dependent K{sup +} (Kv) channels using whole-cell patch clamp technique in freshly isolated rabbit coronary arterial smooth muscle cells. CGS 9343B inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC{sub 50}) value of 0.81 μM. The decay rate of Kv channel inactivation was accelerated by CGS 9343B. The rate constants of association and dissociation for CGS 9343B were 2.77 ± 0.04 μM{sup −1} s{sup −1} and 2.55 ± 1.50 s{sup −1}, respectively. CGS 9343B did not affect the steady-state activation curve, but shifted the inactivation curve toward to a more negative potential. Train pulses (1 or 2 Hz) application progressively increased the CGS 9343B-induced Kv channel inhibition. In addition, the inactivation recovery time constant was increased in the presence of CGS 9343B, suggesting that CGS 9343B-induced inhibition of Kv channel was use-dependent. Another calmodulin inhibitor, W-13, did not affect Kv currents, and did not change the inhibitory effect of CGS 9343B on Kv current. Our results demonstrated that CGS 9343B inhibited Kv currents in a state-, time-, and use-dependent manner, independent of calmodulin inhibition. - Highlights: • We investigated the effects of CGS 9394B on Kv channels. • CGS 9394B inhibited Kv current in a state-, time-, and use-dependent manner. • Caution is required when using CGS 9394B in vascular function studies.

  19. Voltage-dependent BK and Hv1 channels expressed in non-excitable tissues: New therapeutics opportunities as targets in human diseases.

    Science.gov (United States)

    Morera, Francisco J; Saravia, Julia; Pontigo, Juan Pablo; Vargas-Chacoff, Luis; Contreras, Gustavo F; Pupo, Amaury; Lorenzo, Yenisleidy; Castillo, Karen; Tilegenova, Cholpon; Cuello, Luis G; Gonzalez, Carlos

    2015-11-01

    Voltage-gated ion channels are the molecular determinants of cellular excitability. This group of ion channels is one of the most important pharmacological targets in excitable tissues such as nervous system, cardiac and skeletal muscle. Moreover, voltage-gated ion channels are expressed in non-excitable cells, where they mediate key cellular functions through intracellular biochemical mechanisms rather than rapid electrical signaling. This review aims at illustrating the pharmacological impact of these ion channels, highlighting in particular the structural details and physiological functions of two of them - the high conductance voltage- and Ca(2+)-gated K(+) (BK) channels and voltage-gated proton (Hv1) channels- in non-excitable cells. BK channels have been implicated in a variety of physiological processes ranging from regulation of smooth muscle tone to modulation of hormone and neurotransmitter release. Interestingly, BK channels are also involved in modulating K(+) transport in the mammalian kidney and colon epithelium with a potential role in the hyperkalemic phenotype observed in patients with familial hyperkalemic hypertension type 2, and in the pathophysiology of hypertension. In addition, BK channels are responsible for resting and stimulated Ca(2+)-activated K(+) secretion in the distal colon. Hv1 channels have been detected in many cell types, including macrophages, blood cells, lung epithelia, skeletal muscle and microglia. These channels have a central role in the phagocytic system. In macrophages, Hv1 channels participate in the generation of reactive oxygen species in the respiratory burst during the process of phagocytosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Smart gating membranes with in situ self-assembled responsive nanogels as functional gates

    Science.gov (United States)

    Luo, Feng; Xie, Rui; Liu, Zhuang; Ju, Xiao-Jie; Wang, Wei; Lin, Shuo; Chu, Liang-Yin

    2015-10-01

    Smart gating membranes, inspired by the gating function of ion channels across cell membranes, are artificial membranes composed of non-responsive porous membrane substrates and responsive gates in the membrane pores that are able to dramatically regulate the trans-membrane transport of substances in response to environmental stimuli. Easy fabrication, high flux, significant response and strong mechanical strength are critical for the versatility of such smart gating membranes. Here we show a novel and simple strategy for one-step fabrication of smart gating membranes with three-dimensionally interconnected networks of functional gates, by self-assembling responsive nanogels on membrane pore surfaces in situ during a vapor-induced phase separation process for membrane formation. The smart gating membranes with in situ self-assembled responsive nanogels as functional gates show large flux, significant response and excellent mechanical property simultaneously. Because of the easy fabrication method as well as the concurrent enhancement of flux, response and mechanical property, the proposed smart gating membranes will expand the scope of membrane applications, and provide ever better performances in their applications.

  1. Regulation of voltage-gated sodium current by endogenous Src family kinases in cochlear spiral ganglion neurons in culture.

    Science.gov (United States)

    Feng, Shuang; Pflueger, Melissa; Lin, Shuang-Xiu; Groveman, Bradley R; Su, Jiping; Yu, Xian-Min

    2012-04-01

    Voltage-gated sodium (Na+) and potassium (K+)channels have been found to be regulated by Src family kinases(SFKs).However, how these channels are regulated by SFKs in cochlear spiral ganglion neurons (SGNs) remains unknown.Here, we report that altering the activity of endogenous SFKs modulated voltage-gated Na+, but not K+, currents recorded in embryonic SGNs in culture. Voltage-gated Na+ current was suppressed by inhibition of endogenous SFKs or just Src and potentiated by the activation of these enzymes. Detailed investigations showed that under basal conditions, SFK inhibitor application did not significantly affect the voltage-dependent activation, but shifted the steady-state inactivation curves of Na+ currents and delayed the recovery of Na+ currents from inactivation. Application of Src specific inhibitor, Src40–58,not only shifted the inactivation curve but also delayed the recovery of Na+ currents and moved the voltage-dependent activation curve towards the left. The pre-inhibition of SFKs occluded all the effects induced by Src40–58 application, except the left shift of the activation curve. The activation of SFKs did not change either steady-state inactivation or recovery of Na+ currents, but caused the left shift of the activation curve.SFK inhibitor application effectively prevented all the effects induced by SFK activation, suggesting that both the voltage-dependent activation and steady-state inactivation of Na+ current are subjects of SFK regulation. The different effects induced by activation versus inhibition of SFKs implied that under basal conditions, endogenously active and inactive SFKs might be differentially involved in the regulation of voltage-gated Na+ channels in SGNs.

  2. Inflammatory cytokine signaling in insulin producing beta-cells enhances the colocalization correlation coefficient between L-type voltage-dependent calcium channel and calcium-sensing receptor.

    Science.gov (United States)

    Parkash, Jai

    2008-08-01

    The immunological processes in type 1 diabetes and metabolic/inflammatory disorder in type 2 diabetes converge on common signaling pathway(s) leading to beta-cell death in these two diseases. The cytokine-mediated beta-cell death seems to be dependent on voltage-dependent calcium channel (VDCC)-mediated Ca2+ entry. The Ca2+ handling molecular networks control the homeostasis of [Ca2+]i in the beta-cell. The activity and membrane density of VDCC are regulated by several mechanisms including G protein-coupled receptors (GPCRs). CaR is a 123-kDa seven transmembrane extracellular Ca2+ sensing protein that belongs to GPCR family C. Tumor necrosis factor-alpha (TNF-alpha), is a cytokine widely known to activate nuclear factor-kappaB (NF-kappaB) transcription in beta-cells. To obtain a better understanding of TNF-alpha-induced molecular interactions between CaR and VDCC, confocal fluorescence measurements were performed on insulin-producing beta-cells exposed to varying concentrations of TNF-alpha and the results are discussed in the light of increased colocalization correlation coefficient. The insulin producing beta-cells were exposed to 5, 10, 20, 30, and 50 ng/ml TNF-alpha for 24 h at 37 degrees . The cells were then immunolabelled with antibodies directed against CaR, VDCC, and NF-kappaB. The confocal fluorescence imaging data showed enhancement in the colocalization correlation coefficient between CaR and VDCC in beta-cells exposed to TNF-alpha thereby indicating increased membrane delimited spatial interactions between these two membrane proteins. TNF-alpha-induced colocalization of VDCC with CaR was inhibited by nimodipine, an inhibitor of L-type VDCC thereby suggesting that VDCC activity is required for spatial interactions with CaR. The 3-D confocal fluorescence imaging data also demonstrated that addition of TNF-alpha to RIN cells led to the translocation of NF-kappaB from the cytoplasm to the nucleus. Such molecular interactions between CaR and VDCC in tissues

  3. Transcriptional upregulation of α2δ-1 elevates arterial smooth muscle cell voltage-dependent Ca2+ channel surface expression and cerebrovascular constriction in genetic hypertension.

    Science.gov (United States)

    Bannister, John P; Bulley, Simon; Narayanan, Damodaran; Thomas-Gatewood, Candice; Luzny, Patrik; Pachuau, Judith; Jaggar, Jonathan H

    2012-10-01

    A hallmark of hypertension is an increase in arterial myocyte voltage-dependent Ca2+ (CaV1.2) currents that induces pathological vasoconstriction. CaV1.2 channels are heteromeric complexes composed of a pore-forming CaV1.2α1 with auxiliary α2δ and β subunits. Molecular mechanisms that elevate CaV1.2 currents during hypertension and the potential contribution of CaV1.2 auxiliary subunits are unclear. Here, we investigated the pathological significance of α2δ subunits in vasoconstriction associated with hypertension. Age-dependent development of hypertension in spontaneously hypertensive rats was associated with an unequal elevation in α2δ-1 and CaV1.2α1 mRNA and protein in cerebral artery myocytes, with α2δ-1 increasing more than CaV1.2α1. Other α2δ isoforms did not emerge in hypertension. Myocytes and arteries of hypertensive spontaneously hypertensive rats displayed higher surface-localized α2δ-1 and CaV1.2α1 proteins, surface α2δ-1:CaV1.2α1 ratio, CaV1.2 current density and noninactivating current, and pressure- and depolarization-induced vasoconstriction than those of Wistar-Kyoto controls. Pregabalin, an α2δ-1 ligand, did not alter α2δ-1 or CaV1.2α1 total protein but normalized α2δ-1 and CaV1.2α1 surface expression, surface α2δ-1:CaV1.2α1, CaV1.2 current density and inactivation, and vasoconstriction in myocytes and arteries of hypertensive rats to control levels. Genetic hypertension is associated with an elevation in α2δ-1 expression that promotes surface trafficking of CaV1.2 channels in cerebral artery myocytes. This leads to an increase in CaV1.2 current-density and a reduction in current inactivation that induces vasoconstriction. Data also suggest that α2δ-1 targeting is a novel strategy that may be used to reverse pathological CaV1.2 channel trafficking to induce cerebrovascular dilation in hypertension.

  4. A Leucine Zipper Motif Essential for Gating of Hyperpolarization-activated Channels*

    Science.gov (United States)

    Wemhöner, Konstantin; Silbernagel, Nicole; Marzian, Stefanie; Netter, Michael F.; Rinné, Susanne; Stansfeld, Phillip J.; Decher, Niels

    2012-01-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pacemakers in cardiac myocytes and neurons. Although their membrane topology closely resembles that of voltage-gated K+ channels, the mechanism of their unique gating behavior in response to hyperpolarization is still poorly understood. We have identified a highly conserved leucine zipper motif in the S5 segment of HCN family members. In order to study the role of this motif for channel function, the leucine residues of the zipper were individually mutated to alanine, arginine, or glutamine residues. Leucine zipper mutants traffic to the plasma membrane, but the channels lose their sensitivity to open upon hyperpolarization. Thus, our data indicate that the leucine zipper is an important molecular determinant for hyperpolarization-activated channel gating. Residues of the leucine zipper interact with the adjacent S6 segment of the channel. This interaction is essential for voltage-dependent gating of the channel. The lower part of the leucine zipper, at the intracellular mouth of the channel, is important for stabilizing the closed state. Mutations at these sites increase current amplitudes or result in channels with deficient closing and increased min-Po. Our data are further supported by homology models of the open and closed state of the HCN2 channel pore. Thus, we conclude that the leucine zipper of HCN channels is a major determinant for hyperpolarization-activated channel gating. PMID:23048023

  5. Comparative study of the gating motif and C-type inactivation in prokaryotic voltage-gated sodium channels.

    Science.gov (United States)

    Irie, Katsumasa; Kitagawa, Kazuya; Nagura, Hitoshi; Imai, Tomoya; Shimomura, Takushi; Fujiyoshi, Yoshinori

    2010-02-05

    Prokaryotic voltage-gated sodium channels (Na(V)s) are homotetramers and are thought to inactivate through a single mechanism, named C-type inactivation. Here we report the voltage dependence and inactivation rate of the NaChBac channel from Bacillus halodurans, the first identified prokaryotic Na(V), as well as of three new homologues cloned from Bacillus licheniformis (Na(V)BacL), Shewanella putrefaciens (Na(V)SheP), and Roseobacter denitrificans (Na(V)RosD). We found that, although activated by a lower membrane potential, Na(V)BacL inactivates as slowly as NaChBac. Na(V)SheP and Na(V)RosD inactivate faster than NaChBac. Mutational analysis of helix S6 showed that residues corresponding to the "glycine hinge" and "PXP motif" in voltage-gated potassium channels are not obligatory for channel gating in these prokaryotic Na(V)s, but mutations in the regions changed the inactivation rates. Mutation of the region corresponding to the glycine hinge in Na(V)BacL (A214G), Na(V)SheP (A216G), and NaChBac (G219A) accelerated inactivation in these channels, whereas mutation of glycine to alanine in the lower part of helix S6 in NaChBac (G229A), Na(V)BacL (G224A), and Na(V)RosD (G217A) reduced the inactivation rate. These results imply that activation gating in prokaryotic Na(V)s does not require gating motifs and that the residues of helix S6 affect C-type inactivation rates in these channels.

  6. The tyrosine kinase p60c-src regulates the fast gate of the cystic fibrosis transmembrane conductance regulator chloride channel.

    Science.gov (United States)

    Fischer, H; Machen, T E

    1996-12-01

    The role of the tyrosine kinase p60c-src on the gating of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel was investigated with the cell-attached and excised patch clamp technique in conjunction with current noise analysis of recordings containing multiple channels per patch. Spectra of CFTR-generated current noise contained a low-frequency and a high-frequency Lorentzian noise component. In the cell-attached mode, the high-frequency Lorentzian was significantly dependent on the membrane potential, while the low-frequency Lorentzian was unaffected. Excision of forskolin-stimulated patches into ATP-containing solution significantly reduced the amplitude of the voltage-dependent high-frequency Lorentzian. Addition of the tyrosine kinase p60c-src to excised, active, CFTR-containing membrane patches increased mean currents by 54%, increased the corner frequency of the low-frequency Lorentzian, and recovered the high-frequency Lorentzian and its characteristics. Treatment with lambda-phosphatase inactivated src-induced currents and changes in gating. When active patches were excised under conditions in which patch-associated tyrosine phosphatases were blocked with sodium vanadate, the high-frequency gating remained relatively unchanged. The results suggest that CFTR's open probability and its voltage-dependent fast gate are dependent on tyrosine phosphorylation, and that membrane-associated tyrosine phosphatases are responsible for inactivation of the fast gate after patch excision.

  7. Gates controlled parallel-coupled bilayer graphene double quantum dot

    CERN Document Server

    Wang, Lin-Jun; Wei, Da; Cao, Gang; Tu, Tao; Xiao, Ming; Guo, Guang-Can; Chang, A M

    2011-01-01

    Here we report the fabrication and quantum transport measurements of gates controlled parallel-coupled bilayer graphene double quantum dot. It is shown that the interdot coupling strength of the parallel double dots can be effectively tuned from weak to strong regime by both the in-plane plunger gates and back gate. All the relevant energy scales and parameters of the bilayer graphene parallel-coupled double dot can be extracted from the honeycomb charge stability diagrams revealed through the transport measurements.

  8. Gαi2- and Gαi3-specific regulation of voltage-dependent L-type calcium channels in cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Sara Dizayee

    Full Text Available BACKGROUND: Two pertussis toxin sensitive G(i proteins, G(i2 and G(i3, are expressed in cardiomyocytes and upregulated in heart failure. It has been proposed that the highly homologous G(i isoforms are functionally distinct. To test for isoform-specific functions of G(i proteins, we examined their role in the regulation of cardiac L-type voltage-dependent calcium channels (L-VDCC. METHODS: Ventricular tissues and isolated myocytes were obtained from mice with targeted deletion of either Gα(i2 (Gα(i2 (-/- or Gα(i3 (Gα(i3 (-/-. mRNA levels of Gα(i/o isoforms and L-VDCC subunits were quantified by real-time PCR. Gα(i and Ca(vα(1 protein levels as well as protein kinase B/Akt and extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation levels were assessed by immunoblot analysis. L-VDCC function was assessed by whole-cell and single-channel current recordings. RESULTS: In cardiac tissue from Gα(i2 (-/- mice, Gα(i3 mRNA and protein expression was upregulated to 187 ± 21% and 567 ± 59%, respectively. In Gα(i3 (-/- mouse hearts, Gα(i2 mRNA (127 ± 5% and protein (131 ± 10% levels were slightly enhanced. Interestingly, L-VDCC current density in cardiomyocytes from Gα(i2 (-/- mice was lowered (-7.9 ± 0.6 pA/pF, n = 11, p<0.05 compared to wild-type cells (-10.7 ± 0.5 pA/pF, n = 22, whereas it was increased in myocytes from Gα(i3 (-/- mice (-14.3 ± 0.8 pA/pF, n = 14, p<0.05. Steady-state inactivation was shifted to negative potentials, and recovery kinetics slowed in the absence of Gα(i2 (but not of Gα(i3 and following treatment with pertussis toxin in Gα(i3 (-/-. The pore forming Ca(vα(1 protein level was unchanged in all mouse models analyzed, similar to mRNA levels of Ca(vα(1 and Ca(vβ(2 subunits. Interestingly, at the cellular signalling level, phosphorylation assays revealed abolished carbachol-triggered activation of ERK1/2 in mice lacking Gα(i2. CONCLUSION: Our data provide novel evidence for an isoform

  9. Arrangement and mobility of the voltage sensor domain in prokaryotic voltage-gated sodium channels.

    Science.gov (United States)

    Shimomura, Takushi; Irie, Katsumasa; Nagura, Hitoshi; Imai, Tomoya; Fujiyoshi, Yoshinori

    2011-03-04

    Prokaryotic voltage-gated sodium channels (Na(V)s) form homotetramers with each subunit contributing six transmembrane α-helices (S1-S6). Helices S5 and S6 form the ion-conducting pore, and helices S1-S4 function as the voltage sensor with helix S4 thought to be the essential element for voltage-dependent activation. Although the crystal structures have provided insight into voltage-gated K channels (K(V)s), revealing a characteristic domain arrangement in which the voltage sensor domain of one subunit is close to the pore domain of an adjacent subunit in the tetramer, the structural and functional information on Na(V)s remains limited. Here, we show that the domain arrangement in NaChBac, a firstly cloned prokaryotic Na(V), is similar to that in K(V)s. Cysteine substitutions of three residues in helix S4, Q107C, T110C, and R113C, effectively induced intersubunit disulfide bond formation with a cysteine introduced in helix S5, M164C, of the adjacent subunit. In addition, substituting two acidic residues with lysine, E43K and D60K, shifted the activation of the channel to more positive membrane potentials and consistently shifted the preferentially formed disulfide bond from T110C/M164C to Q107C/M164C. Because Gln-107 is located closer to the extracellular side of helix S4 than Thr-110, this finding suggests that the functional shift in the voltage dependence of activation is related to a restriction of the position of helix S4 in the lipid bilayer. The domain arrangement and vertical mobility of helix S4 in NaChBac indicate that the structure and the mechanism of voltage-dependent activation in prokaryotic Na(V)s are similar to those in canonical K(V)s.

  10. A reduced mechanical model for cAMP-modulated gating in HCN channels

    Science.gov (United States)

    Weißgraeber, Stephanie; Saponaro, Andrea; Thiel, Gerhard; Hamacher, Kay

    2017-01-01

    We developed an in silico mechanical model to analyze the process of cAMP-induced conformational modulations in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which conduct cations across the membrane of mammalian heart and brain cells. The structural analysis reveals a quaternary twist in the cytosolic parts of the four subunits in the channel tetramer. This motion augments the intrinsic dynamics of the very same protein structure. The pronounced differences between the cAMP bound and unbound form include a mutual interaction between the C-linker of the cyclic nucleotide binding domain (CNBD) and the linker between the S4 and S5 transmembrane domain of the channel. This allows a mechanistic annotation of the twisting motion in relation to the allosteric modulation of voltage-dependent gating of this channel by cAMP. PMID:28074902

  11. A reduced mechanical model for cAMP-modulated gating in HCN channels

    Science.gov (United States)

    Weißgraeber, Stephanie; Saponaro, Andrea; Thiel, Gerhard; Hamacher, Kay

    2017-01-01

    We developed an in silico mechanical model to analyze the process of cAMP-induced conformational modulations in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which conduct cations across the membrane of mammalian heart and brain cells. The structural analysis reveals a quaternary twist in the cytosolic parts of the four subunits in the channel tetramer. This motion augments the intrinsic dynamics of the very same protein structure. The pronounced differences between the cAMP bound and unbound form include a mutual interaction between the C-linker of the cyclic nucleotide binding domain (CNBD) and the linker between the S4 and S5 transmembrane domain of the channel. This allows a mechanistic annotation of the twisting motion in relation to the allosteric modulation of voltage-dependent gating of this channel by cAMP.

  12. Molecular mechanism of voltage sensing in voltage-gated proton channels

    Science.gov (United States)

    Rebolledo, Santiago; Perez, Marta E.

    2013-01-01

    Voltage-gated proton (Hv) channels play an essential role in phagocytic cells by generating a hyperpolarizing proton current that electrically compensates for the depolarizing current generated by the NADPH oxidase during the respiratory burst, thereby ensuring a sustained production of reactive oxygen species by the NADPH oxidase in phagocytes to neutralize engulfed bacteria. Despite the importance of the voltage-dependent Hv current, it is at present unclear which residues in Hv channels are responsible for the voltage activation. Here we show that individual neutralizations of three charged residues in the fourth transmembrane domain, S4, all reduce the voltage dependence of activation. In addition, we show that the middle S4 charged residue moves from a position accessible from the cytosolic solution to a position accessible from the extracellular solution, suggesting that this residue moves across most of the membrane electric field during voltage activation of Hv channels. Our results show for the first time that the charge movement of these three S4 charges accounts for almost all of the measured gating charge in Hv channels. PMID:23401575

  13. Strong decoherence

    CERN Document Server

    Gell-Mann, Murray; Gell-Mann, Murray; Hartle, James B

    1997-01-01

    We introduce a condition for the strong decoherence of a set of alternative histories of a closed quantum-mechanical system such as the universe. The condition applies, for a pure initial state, to sets of homogeneous histories that are chains of projections, generally branch-dependent. Strong decoherence implies the consistency of probability sum rules but not every set of consistent or even medium decoherent histories is strongly decoherent. Two conditions characterize a strongly decoherent set of histories: (1) At any time the operators that effectively commute with generalized records of history up to that moment provide the pool from which --- with suitable adjustment for elapsed time --- the chains of projections extending history to the future may be drawn. (2) Under the adjustment process, generalized record operators acting on the initial state of the universe are approximately unchanged. This expresses the permanence of generalized records. The strong decoherence conditions (1) and (2) guarantee wha...

  14. Gating-by-Tilt of Mechanically Sensitive Membrane Channels

    Science.gov (United States)

    Turner, Matthew S.; Sens, Pierre

    2004-09-01

    We propose an alternative mechanism for the gating of biological membrane channels in response to membrane tension that involves a change in the slope of the membrane near the channel. Under biological membrane tensions we show that the energy difference between the closed (tilted) and open (untilted) states can far exceed kBT and is comparable to what is available under simple dilational gating. Recent experiments demonstrate that membrane leaflet asymmetries (spontaneous curvature) can strongly affect the gating of some channels. Such a phenomenon would be easier to explain under gating-by-tilt, given its novel intrinsic sensitivity to such asymmetry.

  15. Methodology of Resonant Equiangular Composite Quantum Gates

    Science.gov (United States)

    Low, Guang Hao; Yoder, Theodore J.; Chuang, Isaac L.

    2016-10-01

    The creation of composite quantum gates that implement quantum response functions U ^(θ ) dependent on some parameter of interest θ is often more of an art than a science. Through inspired design, a sequence of L primitive gates also depending on θ can engineer a highly nontrivial U ^ (θ ) that enables myriad precision metrology, spectroscopy, and control techniques. However, discovering new, useful examples of U ^(θ ) requires great intuition to perceive the possibilities, and often brute force to find optimal implementations. We present a systematic and efficient methodology for composite gate design of arbitrary length, where phase-controlled primitive gates all rotating by θ act on a single spin. We fully characterize the realizable family of U ^ (θ ) , provide an efficient algorithm that decomposes a choice of U ^ (θ ) into its shortest sequence of gates, and show how to efficiently choose an achievable U ^(θ ) that, for fixed L , is an optimal approximation to objective functions on its quadratures. A strong connection is forged with classical discrete-time signal processing, allowing us to swiftly construct, as examples, compensated gates with optimal bandwidth that implement arbitrary single-spin rotations with subwavelength spatial selectivity.

  16. A leucine zipper motif essential for gating of hyperpolarization-activated channels.

    Science.gov (United States)

    Wemhöner, Konstantin; Silbernagel, Nicole; Marzian, Stefanie; Netter, Michael F; Rinné, Susanne; Stansfeld, Phillip J; Decher, Niels

    2012-11-23

    It is poorly understood how hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) function. We have identified a leucine zipper in the S5 segment of HCNs, regulating hyperpolarization-activated and instantaneous current components. The leucine zipper is essential for HCN channel gating. The identification and functional characterization of the leucine zipper is an important step toward the understanding of HCN channel function. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pacemakers in cardiac myocytes and neurons. Although their membrane topology closely resembles that of voltage-gated K(+) channels, the mechanism of their unique gating behavior in response to hyperpolarization is still poorly understood. We have identified a highly conserved leucine zipper motif in the S5 segment of HCN family members. In order to study the role of this motif for channel function, the leucine residues of the zipper were individually mutated to alanine, arginine, or glutamine residues. Leucine zipper mutants traffic to the plasma membrane, but the channels lose their sensitivity to open upon hyperpolarization. Thus, our data indicate that the leucine zipper is an important molecular determinant for hyperpolarization-activated channel gating. Residues of the leucine zipper interact with the adjacent S6 segment of the channel. This interaction is essential for voltage-dependent gating of the channel. The lower part of the leucine zipper, at the intracellular mouth of the channel, is important for stabilizing the closed state. Mutations at these sites increase current amplitudes or result in channels with deficient closing and increased min-P(o). Our data are further supported by homology models of the open and closed state of the HCN2 channel pore. Thus, we conclude that the leucine zipper of HCN channels is a major determinant for hyperpolarization-activated channel gating.

  17. Strong Force

    CERN Document Server

    Without the strong force, there could be no life. The carbon in living matter is synthesised in stars via the strong force. Lighter atomic nuclei become bound together in a process called nuclear fusion. A minor change in this interaction would make life impossible. As its name suggests, the strong force is the most powerful of the 4 forces, yet its sphere of influence is limited to within the atomic nucleus. Indeed it is the strong force that holds together the quarks inside the positively charged protons. Without this glue, the quarks would fly apart repulsed by electromagnetism. In fact, it is impossible to separate 2 quarks : so much energy is needed, that a second pair of quarks is produced. Text for the interactive: Can you pull apart the quarks inside a proton?

  18. Allowable Generalized Quantum Gates

    Institute of Scientific and Technical Information of China (English)

    LONG Gui-Lu; LIU Yang; WANG Chuan

    2009-01-01

    In this paper, we give the most general duality gates, or generalized quantum gates in duality quantum computers. Here we show by explicit construction that a n-bit duality quantum computer with d slits can be simulated perfectly with an ordinary quantum computer with n qubits and one auxiliary qudit. Using this model, we give the most general form of duality gates which is of the form Σ(d-1)(i=0)piUi, and the Pi's are complex numbers with module less or equal to I and constrained by |Σipi|≤1.

  19. Beta-scorpion toxin effects suggest electrostatic interactions in domain II of voltage-dependent sodium channels. : Electrostatic interactions between segments IIS2, IIS3 and IIS4 of Na+ channel.

    OpenAIRE

    Mantegazza, Massimo; Cestèle, Sandrine

    2005-01-01

    International audience; Beta-scorpion toxins specifically modulate the voltage dependence of sodium channel activation by acting through a voltage-sensor trapping model. We used mutagenesis, functional analysis and the action of beta-toxin as tools to investigate the existence and role in channel activation of molecular interactions between the charged residues of the S2, S3 and S4 segments in domain II of sodium channels. Mutating to arginine the acidic residues of the S2 and S3 transmembran...

  20. Automatic parameter extraction technique for gate leakage current modeling in double gate MOSFET

    Science.gov (United States)

    Darbandy, Ghader; Gneiting, Thomas; Alius, Heidrun; Alvarado, Joaquín; Cerdeira, Antonio; Iñiguez, Benjamin

    2013-11-01

    Direct Tunneling (DT) and Trap Assisted Tunneling (TAT) gate leakage current parameters have been extracted and verified considering automatic parameter extraction approach. The industry standard package IC-CAP is used to extract our leakage current model parameters. The model is coded in Verilog-A and the comparison between the model and measured data allows to obtain the model parameter values and parameters correlations/relations. The model and parameter extraction techniques have been used to study the impact of parameters in the gate leakage current based on the extracted parameter values. It is shown that the gate leakage current depends on the interfacial barrier height more strongly than the barrier height of the dielectric layer. There is almost the same scenario with respect to the carrier effective masses into the interfacial layer and the dielectric layer. The comparison between the simulated results and available measured gate leakage current transistor characteristics of Trigate MOSFETs shows good agreement.

  1. Slide Gate Bricks

    Institute of Scientific and Technical Information of China (English)

    Wang Jing; Peng Xigao

    2010-01-01

    @@ 1 Scope This standard specifies the classification,shape,dimension,technical requirements,test methods,quality appraisal procedures,packing,marking,transportation,storage,and quality certificate of slide gate bricks.

  2. Ultrafast Quantum Gates in Circuit QED

    CERN Document Server

    Romero, G; Wang, Y M; Scarani, V; Solano, E

    2011-01-01

    We present a method of implementing ultrafast two-qubit gates valid for the ultrastrong coupling (USC) and deep strong coupling (DSC) regimes of light-matter interaction, considering state-of-the-art circuit quantum electrodynamics (QED) technology. Our proposal includes a suitable qubit architecture and is based on a four-step sequential displacement of an intracavity mode, operating at a time proportional to the inverse of the resonator frequency. Through ab initio calculations, we show that these quantum gates can be performed at subnanosecond time scales, while keeping the fidelity above 99%.

  3. Advantages of gated silicon single photon detectors

    CERN Document Server

    Lunghi, T; Barreiro, C; Stucki, D; Sanguinetti, B; Zbinden, H

    2012-01-01

    We present a gated silicon single photon detector based on a commercially available avalanche photodiode. Our detector achieves a photon detection efficiency of 45\\pm5% at 808 nm with 2x 10^-6 dark count per ns at -30V of excess bias and -30{\\deg}C. We compare gated and free-running detectors and show that this mode of operation has significant advantages in two representative experimental scenarios: detecting a single photon either hidden in faint continuous light or after a strong pulse. We also explore, at different temperatures and incident light intensities, the "charge persistence" effect, whereby a detector clicks some time after having been illuminated.

  4. Being flexible: the voltage-controllable activation gate of Kv channels

    Directory of Open Access Journals (Sweden)

    Alain J. Labro

    2012-09-01

    Full Text Available Kv channels form voltage-dependent potassium selective pores in the outer cell membrane and are composed out of four -subunits, each having six membrane-spanning -helices (S1-S6. The -subunits tetramerize such that the S5-S6 pore domains co-assemble into a centrally located K+ pore which is surrounded by four operational voltage sensing domains (VSD that are each formed by the S1-S4 segments. Consequently, each subunit is capable of responding to changes in membrane potential and dictates whether the pore should be conductive or not. K+ permeation through the pore can be sealed off by two separate gates in series: (a at the inner S6 bundle crossing (BC gate and (b at the level of the selectivity-filter (SF gate located at the extracellular entrance of the pore. Within the last years a general consensus emerged that a direct communication between the S4S5-linker and the bottom part of S6 (S6c constitutes the coupling with the VSD thus making the BC gate the main voltage-controllable activation gate. While the BC gate listens to the VSD, the SF changes its conformation depending on the status of the BC gate. Through the eyes of an entering K+ ion, the operation of the BC gate apparatus can be compared with the iris-like motion of the diaphragm from a camera whereby its diameter widens. Two main gating motions have been proposed to create this BC gate widening: (1 tilting of the helix whereby the S6 converts from a straight -helix to a tilted one or (2 swiveling of the S6c whereby the S6 remains bent. Such motions require a flexible hinge that decouples the pre- and post-hinge segment. Roughly at the middle of the S6 there exists a highly conserved glycine residue and a tandem proline motif that seem to fulfill the role of a gating hinge which allows for tilting/swiveling/rotations of the post-hinge S6 segment. In this review we delineate our current view on the operation of the BC gate for controlling K+ permeation in Kv channels.

  5. Advanced insulated gate bipolar transistor gate drive

    Science.gov (United States)

    Short, James Evans; West, Shawn Michael; Fabean, Robert J.

    2009-08-04

    A gate drive for an insulated gate bipolar transistor (IGBT) includes a control and protection module coupled to a collector terminal of the IGBT, an optical communications module coupled to the control and protection module, a power supply module coupled to the control and protection module and an output power stage module with inputs coupled to the power supply module and the control and protection module, and outputs coupled to a gate terminal and an emitter terminal of the IGBT. The optical communications module is configured to send control signals to the control and protection module. The power supply module is configured to distribute inputted power to the control and protection module. The control and protection module outputs on/off, soft turn-off and/or soft turn-on signals to the output power stage module, which, in turn, supplies a current based on the signal(s) from the control and protection module for charging or discharging an input capacitance of the IGBT.

  6. Potentiation of prolactin secretion following lactotrope escape from dopamine action. II. Phosphorylation of the alpha(1) subunit of L-type, voltage-dependent calcium channels.

    Science.gov (United States)

    Hernández, M E; del Mar Hernández, M; Díaz-Muñoz, M; Clapp, C; de la Escalera, G M

    1999-07-01

    Modulation of Ca(2+) channels has been shown to alter cellular functions. It can play an important role in the amplification of signals in the endocrine system, including the pleiotropically regulated pituitary lactotropes. Prolactin (PRL) secretion is tonically inhibited by dopamine (DA), the escape from which triggers acute episodes of hormone secretion. The magnitude of these episodes is explained by a potentiation of the PRL-releasing action of secretagogues such as thyrotropin-releasing hormone (TRH). While the mechanisms of this potentiation are not fully understood, it is known to be mimicked by the dihydropyridine, L-type Ca(2+) channel agonist Bay K 8644 and blocked by nifedipine and methoxyverapamil. The potentiation is also blocked by inhibitors of cyclic AMP-dependent protein kinase and protein kinase C. We recently described that the escape from tonic actions of DA results in increased macroscopic Ca(2+) currents in GH(4)C(1) lactotropic clonal cells transfected with a cDNA encoding the long form of the human D(2)-DA receptor. Here we show that the withdrawal from DA potentiates the PRL-releasing action of TRH in GH(4)C(1)/D(2)-DAR cells to the same extent as in enriched lactotropes in primary culture. In both experimental models a low density of dihydropyridine receptors was shown by (+)-[(3)H]PN200-110 binding. Photoaffinity labelling with the dihydropyridine [(3)H]azidopine revealed a protein consistent with the alpha(1) subunit of L-type Ca(2+) channels of 165-170 kDa. In both experimental models, the facilitation of TRH action triggered by the escape from DA was correlated with an enhanced rate of phosphorylation of this putative alpha(1) subunit, the nature of which was further supported by immunoprecipitation with selective antibodies directed against the alpha(1C) and alpha(1D) subunit of voltage-gated calcium channels. We propose that PKA- and PKC-dependent phosphorylation of the alpha(1) subunit of high voltage activated, L-type Ca(2

  7. The sea anemone Bunodosoma caissarum toxin BcIII modulates the sodium current kinetics of rat dorsal root ganglia neurons and is displaced in a voltage-dependent manner.

    Science.gov (United States)

    Salceda, Emilio; López, Omar; Zaharenko, André J; Garateix, Anoland; Soto, Enrique

    2010-03-01

    Sea anemone toxins bind to site 3 of the sodium channels, which is partially formed by the extracellular linker connecting S3 and S4 segments of domain IV, slowing down the inactivation process. In this work we have characterized the actions of BcIII, a sea anemone polypeptide toxin isolated from Bunodosoma caissarum, on neuronal sodium currents using the patch clamp technique. Neurons of the dorsal root ganglia of Wistar rats (P5-9) in primary culture were used for this study (n=65). The main effects of BcIII were a concentration-dependent increase in the sodium current inactivation time course (IC(50)=2.8 microM) as well as an increase in the current peak amplitude. BcIII did not modify the voltage at which 50% of the channels are activated or inactivated, nor the reversal potential of sodium current. BcIII shows a voltage-dependent action. A progressive acceleration of sodium current fast inactivation with longer conditioning pulses was observed, which was steeper as more depolarizing were the prepulses. The same was observed for other two anemone toxins (CgNa, from Condylactis gigantea and ATX-II, from Anemonia viridis). These results suggest that the binding affinity of sea anemone toxins may be reduced in a voltage-dependent manner, as has been described for alpha-scorpion toxins.

  8. Chronic electroconvulsive stimulation but not chronic restraint stress modulates mRNA expression of voltage-dependent potassium channels Kv7.2 and Kv11.1 in the rat piriform cortex

    DEFF Research Database (Denmark)

    Hjæresen, Marie-Louise; Hageman, Ida; Plenge, Per

    2008-01-01

    The mechanisms by which stress and electroconvulsive therapy exert opposite effects on the course of major depression are not known. Potential candidates might include the voltage-dependent potassium channels. Potassium channels play an important role in maintaining the resting membrane potential...... and controlling neuronal excitability. To explore this hypothesis, we examined the effects of one or several electroconvulsive stimulations and chronic restraint stress (6 h/day for 21 days) on the expression of voltage-dependent potassium channel Kv7.2, Kv11.1, and Kv11.3 mRNA in the rat brain using in situ...... hybridization. Repeated, but not acute, electroconvulsive stimulation increased Kv7.2 and Kv11.1 mRNA levels in the piriform cortex. In contrast, restraint stress had no significant effect on mRNA expression of Kv7.2, Kv11.1, or Kv11.3 in any of the brain regions examined. Thus, it appears that the investigated...

  9. State-dependent blocker interactions with the CFTR chloride channel: implications for gating the pore.

    Science.gov (United States)

    Linsdell, Paul

    2014-12-01

    Chloride permeation through the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is subject to voltage-dependent open-channel block by a diverse range of cytoplasmic anions. However, in most cases the ability of these blocking substances to influence the pore opening and closing process has not been reported. In the present work, patch clamp recording was used to investigate the state-dependent block of CFTR by cytoplasmic Pt(NO2)4(2-) ions. Two major effects of Pt(NO2)4(2-) were identified. First, this anion caused fast, voltage-dependent block of open channels, leading to an apparent decrease in single-channel current amplitude. Secondly, Pt(NO2)4(2-) also decreased channel open probability due to an increase in interburst closed times. Interestingly, mutations in the pore that weakened (K95Q) or strengthened (I344K, V345K) interactions with Pt(NO2)4(2-) altered blocker effects both on Cl(-) permeation and on channel gating, suggesting that both these effects are a consequence of Pt(NO2)4(2-) interaction with a single site within the pore. Experiments at reduced extracellular Cl(-) concentration hinted that Pt(NO2)4(2-) may have a third effect, possibly increasing channel activity by interfering with channel closure. These results suggest that Pt(NO2)4(2-) can enter from the cytoplasm into the pore inner vestibule of both open and closed CFTR channels, and that Pt(NO2)4(2-) bound in the inner vestibule blocks Cl(-) permeation as well as interfering with channel opening and, perhaps, channel closure. Implications for the location of the channel gate in the pore, and the operation of this gate, are discussed.

  10. A nanomechanical Fredkin gate.

    Science.gov (United States)

    Wenzler, Josef-Stefan; Dunn, Tyler; Toffoli, Tommaso; Mohanty, Pritiraj

    2014-01-08

    Irreversible logic operations inevitably discard information, setting fundamental limitations on the flexibility and the efficiency of modern computation. To circumvent the limit imposed by the von Neumann-Landauer (VNL) principle, an important objective is the development of reversible logic gates, as proposed by Fredkin, Toffoli, Wilczek, Feynman, and others. Here, we present a novel nanomechanical logic architecture for implementing a Fredkin gate, a universal logic gate from which any reversible computation can be built. In addition to verifying the truth table, we demonstrate operation of the device as an AND, OR, NOT, and FANOUT gate. Excluding losses due to resonator dissipation and transduction, which will require significant improvement in order to minimize the overall energy cost, our device requires an energy of order 10(4) kT per logic operation, similar in magnitude to state-of-the-art transistor-based technologies. Ultimately, reversible nanomechanical logic gates could play a crucial role in developing highly efficient reversible computers, with implications for efficient error correction and quantum computing.

  11. The Gates at Pipe Spring National Monument, Arizona (gates)

    Data.gov (United States)

    National Park Service, Department of the Interior — This is an Arc/Info coverage consisting of 7 points representing gates at Pipe Spring National Monument, Arizona. The gates were collected by a Trimble GeoXT GPS...

  12. Amplifying genetic logic gates.

    Science.gov (United States)

    Bonnet, Jerome; Yin, Peter; Ortiz, Monica E; Subsoontorn, Pakpoom; Endy, Drew

    2013-05-03

    Organisms must process information encoded via developmental and environmental signals to survive and reproduce. Researchers have also engineered synthetic genetic logic to realize simpler, independent control of biological processes. We developed a three-terminal device architecture, termed the transcriptor, that uses bacteriophage serine integrases to control the flow of RNA polymerase along DNA. Integrase-mediated inversion or deletion of DNA encoding transcription terminators or a promoter modulates transcription rates. We realized permanent amplifying AND, NAND, OR, XOR, NOR, and XNOR gates actuated across common control signal ranges and sequential logic supporting autonomous cell-cell communication of DNA encoding distinct logic-gate states. The single-layer digital logic architecture developed here enables engineering of amplifying logic gates to control transcription rates within and across diverse organisms.

  13. Switching teraherz waves with gate-controlled active graphene metamaterials

    CERN Document Server

    Lee, Seung Hoon; Kim, Teun-Teun; Lee, Seungwoo; Liu, Ming; Yin, Xiaobo; Choi, Hong Kyw; Lee, Seung S; Choi, Choon-Gi; Choi, Sung-Yool; Zhang, Xiang; Min, Bumki

    2012-01-01

    The extraordinary electronic properties of graphene, such as its continuously gate-variable ambipolar field effect and the resulting steep change in resistivity, provided the main thrusts for the rapid advance of graphene electronics. The gate-controllable electronic properties of graphene provide a route to efficiently manipulate the interaction of low-energy photons with massless Dirac fermions, which has recently sparked keen interest in graphene plasmonics. However, the electro-optic tuning capability of unpatterned graphene alone is still not strong enough for practical optoelectronic applications due to its nonresonant Drude-like behaviour. Here, we experimentally demonstrate that substantial gate-induced persistent switching and linear modulation of terahertz waves can be achieved in a two-dimensional artificial material, referred to as a metamaterial, into which an atomically thin, gated two-dimensional graphene layer is integrated. The gate-controllable light-matter interaction in the graphene layer ...

  14. <strong>Mini-project>

    DEFF Research Database (Denmark)

    Katajainen, Jyrki

    2008-01-01

    In this project the goal is to develop the safe * family of containers for the CPH STL. The containers to be developed should be safer and more reliable than any of the existing implementations. A special focus should be put on strong exception safety since none of the existing prototypes available...... at the CPH STL can give this guarantee for all operations. In spite of the safety requirements, the strict running-time requirements specified in the C++ standard, and additional requirements specified in the CPH STL design documents, must be fulfilled....

  15. Plasmonic response of partially gated field effect transistors

    Science.gov (United States)

    Rudin, S.; Rupper, G.; Reed, M. L.; Shur, M.

    2016-09-01

    Electron density oscillations in the transistor channels - plasma waves in the two-dimensional electron gas - determine the high frequency device response. Plasmonic field effect transistors have emerged as very sensitive, tunable, and extremely fast detectors of THz radiation. They have been implemented using silicon (CMOS), AlGaAs/InGaAs HEMTs, and AlGaAs/InGaAs HEMTs, with the HEMTs shown to operate more efficiently at higher THz frequencies. These HEMTs have both gated and ungated sections of the device channel between the source and drain, and the photovoltaic regime of operation requires an asymmetric gate placement in the device channel. The interactions of the plasma waves in the gated and ungated channel regions strongly affect the overall response and have been investigated in numerous publications. This work addresses a new aspect of such interaction - the effect of the relative position of the gated and ungated section. We show this previously unexplored effect plays a dominant role in determining the response. The results of the numerical simulation based on the solution of the complete system of the hydrodynamic equations describing the electron fluid in the device channel show that the inverse response frequency could be approximated by the sum of the gated plasmon transit time in the gated section of the device, the ungated plasmon transit time in the ungated section of the device between the gate and the drain, and the RC gate-to-source constant. Here R and C are the resistance and capacitance of the gate to source section. Hence, the highest speed is achieved when the gate is as close to the source as possible. This suggests a novel plasmonic detector design, where the gate and source electrode overlap, which is shown to have a superior frequency response for the same distance between the source and the drain.

  16. Gated currents in isolated olfactory receptor neurons of the larval tiger salamander.

    Science.gov (United States)

    Firestein, S; Werblin, F S

    1987-09-01

    The electrical properties of enzymatically isolated olfactory receptor cells were studied with whole-cell patch clamp. Voltage-dependent currents could be separated into three ionic components: a transient inward sodium current, a sustained inward calcium current, and an outward potassium current. Three components of the outward current could be identified by their gating and kinetics: a calcium-dependent potassium current [IK(Ca)], a voltage-dependent potassium current [IK(V)], and a transient potassium current (Ia). Typical resting potentials were near -54 mV, and typical input resistance was 3-6 G omega. Thus, only 3 pA of injected current was required to depolarize the cell to spike threshold near -45 mV. The response to a current step consisted of either a single spike regardless of stimulus strength, or a train of less than 8 spikes, decrementing in amplitude and frequency over approximately equal to 250 msec. Thus, the receptor response cannot be finely graded with stimulus intensity.

  17. Scanning Gate Spectroscopy on Nanoclusters

    OpenAIRE

    Gurevich, L.; Canali, L.; Kouwenhoven, L.P.

    1999-01-01

    A gated probe for scanning tunnelling microscopy (STM) has been developed. The probe extends normal STM operations by means of an additional electrode fabricated next to the tunnelling tip. The extra electrode does not make contact with the sample and can be used as a gate. We report on the recipe used for fabricating the tunnelling tip and the gate electrode on a silicon nitride cantilever. We demonstrate the functioning of the scanning gate probes by performing single-electron tunnelling sp...

  18. Voltage-dependent capacitance behavior and underlying mechanisms in metal-insulator-metal capacitors with Al2O3-ZrO2-SiO2 nano-laminates

    Science.gov (United States)

    Zhu, Bao; Liu, Wen-Jun; Wei, Lei; Ding, Shi-Jin

    2016-04-01

    Nano-laminates consisting of high-permittivity dielectrics and SiO2 have been extensively studied for radio frequency metal-insulator-metal (MIM) capacitors because of their superior voltage linearity and low leakage current. However, there are no reports on the capacitance-voltage (C-V) characteristics at a high sweep voltage range. In this work, an interesting variation in the voltage-dependent capacitance that forms a ‘ω’-like shape is demonstrated for the MIM capacitors with Al2O3/ZrO2/SiO2 nano-laminates. As the thickness ratio of the SiO2 film to the total insulator increases to around 0.15, the C-V curve changes from an upward parabolic shape to a ‘ω’ shape. This can be explained based on the competition between the orientation polarization from SiO2 and the electrode polarization from Al2O3 and ZrO2. When the SiO2 film is very thin, the electrode polarization dominates in the MIM capacitor, generating a positive curvature C-V curve. When the thickness of SiO2 is increased, the orientation polarization is enhanced and thus both polarizations are operating in the MIM capacitors. This leads to the appearance of a multiple domain C-V curve containing positive and negative curvatures. Therefore, good consistency between the experimental results and the theoretical simulations is demonstrated. Such voltage-dependent capacitance behavior is not determined by the stack structure of the insulator, measurement frequency and oscillator voltage, but by the thickness ratio of the SiO2 film to the whole insulator. These findings are helpful to engineer MIM capacitors with good voltage linearity.

  19. Stanford, Duke, Rice,... and Gates?

    Science.gov (United States)

    Carey, Kevin

    2009-01-01

    This article presents an open letter to Bill Gates. In his letter, the author suggests that Bill Gates should build a brand-new university, a great 21st-century institution of higher learning. This university will be unlike anything the world has ever seen. He asks Bill Gates not to stop helping existing colleges create the higher-education system…

  20. Stanford, Duke, Rice,... and Gates?

    Science.gov (United States)

    Carey, Kevin

    2009-01-01

    This article presents an open letter to Bill Gates. In his letter, the author suggests that Bill Gates should build a brand-new university, a great 21st-century institution of higher learning. This university will be unlike anything the world has ever seen. He asks Bill Gates not to stop helping existing colleges create the higher-education system…

  1. The four-gate transistor

    Science.gov (United States)

    Mojarradi, M. M.; Cristoveanu, S.; Allibert, F.; France, G.; Blalock, B.; Durfrene, B.

    2002-01-01

    The four-gate transistor or G4-FET combines MOSFET and JFET principles in a single SOI device. Experimental results reveal that each gate can modulate the drain current. Numerical simulations are presented to clarify the mechanisms of operation. The new device shows enhanced functionality, due to the combinatorial action of the four gates, and opens rather revolutionary applications.

  2. Influence of back-gate stress on the back-gate threshold voltage of a LOCOS-isolated SOI MOSFET

    Institute of Scientific and Technical Information of China (English)

    梅博; 毕津顺; 李多力; 刘思南; 韩郑生

    2012-01-01

    The performance of a LOCOS-isolated SOI MOSFET heavily depends on its back-gate characteristic, which can be affected by back-gate stress,A large voltage stress was applied to the back gate of SOI devices for at least 30 s at room temperature,which could effectively modify the back-gate threshold voltage of these devices.This modification is stable and time invariant.In order to improve the back-gate threshold voltage,positive substrate bias was applied to NMOS devices and negative substrate bias was applied to PMOS devices,These results suggest that there is a leakage path between source and drain along the silicon island edge,and the application of large backgate bias with the source,drain and gate grounded can strongly affect this leakage path.So we draw the conclusion that the back-gate threshold voltage,which is directly related to the leakage current,can be influenced by back-gate stress.

  3. Advantages of gated silicon single photon detectors

    Science.gov (United States)

    Legré, Matthieu; Lunghi, Tommaso; Stucki, Damien; Zbinden, Hugo

    2013-05-01

    We present gated silicon single photon detectors based on two commercially available avalanche photodiodes (APDs) and one customised APD from ID Quantique SA. This customised APD is used in a commercially available device called id110. A brief comparison of the two commercial APDs is presented. Then, the charge persistence effect of all of those detectors that occurs just after a strong illumination is shown and discussed.

  4. Deciphering voltage-gated Na(+) and Ca(2+) channels by studying prokaryotic ancestors.

    Science.gov (United States)

    Catterall, William A; Zheng, Ning

    2015-09-01

    Voltage-gated sodium channels (NaVs) and calcium channels (CaVs) are involved in electrical signaling, contraction, secretion, synaptic transmission, and other physiological processes activated in response to depolarization. Despite their physiological importance, the structures of these closely related proteins have remained elusive because of their size and complexity. Bacterial NaVs have structures analogous to a single domain of eukaryotic NaVs and CaVs and are their likely evolutionary ancestor. Here we review recent work that has led to new understanding of NaVs and CaVs through high-resolution structural studies of their prokaryotic ancestors. New insights into their voltage-dependent activation and inactivation, ion conductance, and ion selectivity provide realistic structural models for the function of these complex membrane proteins at the atomic level. Published by Elsevier Ltd.

  5. Dysfunctional Hyperpolarization-Activated Cyclic Nucleotide-gated Ion Channels in Cardiac Diseases

    Directory of Open Access Journals (Sweden)

    Xiaoqi Zhao

    Full Text Available Abstract Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are reverse voltage-dependent, and their activation depends on the hyperpolarization of the membrane and may be directly or indirectly regulated by the cyclic adenosine monophosphate (cAMP or other signal-transduction cascades. The distribution, quantity and activation states of HCN channels differ in tissues throughout the body. Evidence exhibits that HCN channels play critical roles in the generation and conduction of the electrical impulse and the physiopathological process of some cardiac diseases. They may constitute promising drug targets in the treatment of these cardiac diseases. Pharmacological treatment targeting HCN channels is of benefit to these cardiac conditions.

  6. High permittivity gate dielectric materials

    CERN Document Server

    2013-01-01

    "The book comprehensively covers all the current and the emerging areas of the physics and the technology of high permittivity gate dielectric materials, including, topics such as MOSFET basics and characteristics, hafnium-based gate dielectric materials, Hf-based gate dielectric processing, metal gate electrodes, flat-band and threshold voltage tuning, channel mobility, high-k gate stack degradation and reliability, lanthanide-based high-k gate stack materials, ternary hafnia and lanthania based high-k gate stack films, crystalline high-k oxides, high mobility substrates, and parameter extraction. Each chapter begins with the basics necessary for understanding the topic, followed by a comprehensive review of the literature, and ultimately graduating to the current status of the technology and our scientific understanding and the future prospects."

  7. Hetero-gate-Dielectric Symmetric U-shaped gate tunnel FET

    Science.gov (United States)

    Tajally, Mohammad Bagher; Karami, Mohammad Azim

    2017-10-01

    Heterogeneous gate dielectric is used in a nanoscale symmetric U-shaped gate tunnel FET (SUTFET), which resulted in ION, IOFF, subthreshold swing (SS), and Iambipolar enhancement. ION of 1.5 × 10-5 A/μm, IOFF of 6 × 10-12 A/μm, average subthreshold swing of (SS) 19.83 mV/decade from 0 V high-k dielectric close to the source and low-k dielectric in the vicinity of drain. The gate dielectric engineering shows characteristic enhancement in compare to SUTFET with single gate dielectric material. The strong coupling between the gate and transistor channel near the source results in reduced potential barrier width in tunnel junction, which leads to higher ION and lower subthreshold swing. Moreover, the presence of low-k dielectric near the drain reduces ambipolar current by increasing potential barrier height. This improved SUTFET characteristics makes it suitable for the usage in digital circuits due to reduced ambipolar response.

  8. Gating currents from a Kv3 subfamily potassium channel: charge movement and modification by BDS-II toxin.

    Science.gov (United States)

    Wang, Zhuren; Robertson, Brian; Fedida, David

    2007-11-01

    Kv3 channels have a major role in determining neuronal excitability, and are characterized by ultra-rapid kinetics of gating and a high activation threshold. However, the gating currents, which occur as a result of positional changes of the charged elements in the channel structure during activation, are not well understood. Here we report a study of gating currents from wild-type Kv3.2b channels, expressed in human embryonic kidney (HEK) cells to facilitate high time-resolution recording. On-gating currents (I(g,on)) had extremely rapid kinetics such that at +80 mV, the time constant for the decay of I(g,on) was only approximately 0.3 ms. Decay of I(g,on) appeared mono-exponential at all potentials studied, and in support of this, the charge-voltage (Q-V) relationship was fitted with a single Boltzmann function, supporting the idea that only one charge system is required to account for the time course of I(g,on) and the voltage dependence of Q(on). The voltage (V((1/2))) for half movement of gating charge was -8.4 +/- 4.0 mV (n = 6), which closely matches the voltage dependence of activation of Kv3.2b ionic currents reported before. Depolarizations to more positive potentials than 0 mV decreased the amplitude and slowed the decay of the off-gating currents (I(g,off)), suggesting that a rate-limiting step in opening was present in Kv3 channels as in Shaker and other Kv channels. Return of charge was negatively shifted along the potential axis with a V((1/2)) of Q(off) of -80.9 +/- 0.8 mV (n = 3), which allowed approximately 90% charge return upon repolarization to -100 mV. BDS-II toxin apparently reduced I(g,on), and greatly slowed the kinetics of I(g,on), while shifting the Q-V relationship in the depolarizing direction. However, the Q-V relationship remained well fitted by a single Boltzmann function. These data provide the first description of Kv3 gating currents and give further insight into the interaction of BDS toxins and Kv3 channels.

  9. Dihydropyridine receptors actively control gating of ryanodine receptors in resting mouse skeletal muscle fibres

    Science.gov (United States)

    Robin, Gaëlle; Allard, Bruno

    2012-01-01

    Contraction of skeletal muscle is triggered by the release of Ca2+ from the sarcoplasmic reticulum (SR) in response to depolarization of the muscle membrane. Depolarization is known to elicit a conformational change of the dihydropyridine receptor (DHPR) in the tubular membrane that controls in a time- and voltage-dependent manner the opening of the ryanodine receptor (RyR), the SR Ca2+ release channel. At rest, it is assumed that RyRs are kept in a closed state imposed by the repressive action of DHPRs; however, a direct control of the RyR gating by the DHPR has up to now never been demonstrated in resting adult muscle. In this study, we monitored slow changes in SR Ca2+ content using the Ca2+ indicator fluo-5N loaded in the SR of voltage-clamped mouse muscle fibres. We first show that external Ca2+ removal induced a reversible SR Ca2+ efflux at −80 mV and prevented SR Ca2+ refilling following depolarization-evoked SR Ca2+ depletion. The dihydropyridine compound nifedipine induced similar effects. The rate of SR Ca2+ efflux was also shown to be controlled in a time- and voltage-dependent manner within a membrane potential range more negative than −50 mV. Finally, intracellular addition of ryanodine produced an irreversible SR Ca2+ efflux and kept the SR in a highly depleted state following depolarization-evoked SR Ca2+ depletion. The fact that resting SR Ca2+ efflux is modulated by conformational changes of DHPRs induced by external Ca2+, nifedipine and voltage demonstrates that DHPRs exert an active control on gating of RyRs in resting skeletal muscle. PMID:23006480

  10. Transient Receptor Potential Vanilloid 4-Induced Modulation of Voltage-Gated Sodium Channels in Hippocampal Neurons.

    Science.gov (United States)

    Hong, Zhiwen; Jie, Pinghui; Tian, Yujing; Chen, Tingting; Chen, Lei; Chen, Ling

    2016-01-01

    Transient receptor potential vanilloid 4 (TRPV4) is reported to control the resting membrane potential and increase excitability in many types of cells. Voltage-gated sodium channels (VGSCs) play an important role in initiating action potentials in neurons. However, whether VGSCs can be modulated by the activation of TRPV4 in hippocampal pyramidal neurons remains unknown. In this study, we tested the effect of TRPV4 agonists (GSK1016790A and 4α-PDD) on voltage-gated sodium current (I Na) in hippocampal CA1 pyramidal neurons and the protein levels of α/β-subunit of VGSCs in the hippocampus of mice subjected to intracerebroventricular (icv.) injection of GSK1016790A (GSK-injected mice). Herein, we report that I Na was inhibited by acute application of GSK1016790A or 4α-PDD. In the presence of TRPV4 agonists, the voltage-dependent inactivation curve shifted to the hyperpolarization, whereas the voltage-dependent activation curve remained unchanged. The TRPV4 agonist-induced inhibition of I Na was blocked by the TRPV4 antagonist or tetrodotoxin. Moreover, blocking protein kinase A (PKA) markedly attenuated the GSK1016790A-induced inhibition of I Na, whereas antagonism of protein kinase C or p38 mitogen-activated protein kinase did not change GSK1016790A action. Finally, the protein levels of Nav1.1, Nav1.2, and Nav1.6 in the hippocampus increased in GSK-injected mice, whereas those of Nav1.3 and Navβ1 remained nearly unchanged. We conclude that I Na is inhibited by the acute activation of TRPV4 through PKA signaling pathway in hippocampal pyramidal neurons, but protein expression of α-subunit of VGSCs is increased by sustained TRPV4 activation, which may compensate for the acute inhibition of I Na and provide a possibility for hyper-excitability upon sustained TRPV4 activation.

  11. Photocontrol of Voltage-Gated Ion Channel Activity by Azobenzene Trimethylammonium Bromide in Neonatal Rat Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Sheyda R Frolova

    Full Text Available The ability of azobenzene trimethylammonium bromide (azoTAB to sensitize cardiac tissue excitability to light was recently reported. The dark, thermally relaxed trans- isomer of azoTAB suppressed spontaneous activity and excitation propagation speed, whereas the cis- isomer had no detectable effect on the electrical properties of cardiomyocyte monolayers. As the membrane potential of cardiac cells is mainly controlled by activity of voltage-gated ion channels, this study examined whether the sensitization effect of azoTAB was exerted primarily via the modulation of voltage-gated ion channel activity. The effects of trans- and cis- isomers of azoTAB on voltage-dependent sodium (INav, calcium (ICav, and potassium (IKv currents in isolated neonatal rat cardiomyocytes were investigated using the whole-cell patch-clamp technique. The experiments showed that azoTAB modulated ion currents, causing suppression of sodium (Na+ and calcium (Ca2+ currents and potentiation of net potassium (K+ currents. This finding confirms that azoTAB-effect on cardiac tissue excitability do indeed result from modulation of voltage-gated ion channels responsible for action potential.

  12. Ephaptic coupling rescues conduction failure in weakly coupled cardiac tissue with voltage-gated gap junctions

    Science.gov (United States)

    Weinberg, S. H.

    2017-09-01

    Electrical conduction in cardiac tissue is usually considered to be primarily facilitated by gap junctions, providing a pathway between the intracellular spaces of neighboring cells. However, recent studies have highlighted the role of coupling via extracellular electric fields, also known as ephaptic coupling, particularly in the setting of reduced gap junction expression. Further, in the setting of reduced gap junctional coupling, voltage-dependent gating of gap junctions, an oft-neglected biophysical property in computational studies, produces a positive feedback that promotes conduction failure. We hypothesized that ephaptic coupling can break the positive feedback loop and rescue conduction failure in weakly coupled cardiac tissue. In a computational tissue model incorporating voltage-gated gap junctions and ephaptic coupling, we demonstrate that ephaptic coupling can rescue conduction failure in weakly coupled tissue. Further, ephaptic coupling increased conduction velocity in weakly coupled tissue, and importantly, reduced the minimum gap junctional coupling necessary for conduction, most prominently at fast pacing rates. Finally, we find that, although neglecting gap junction voltage-gating results in negligible differences in well coupled tissue, more significant differences occur in weakly coupled tissue, greatly underestimating the minimal gap junctional coupling that can maintain conduction. Our study suggests that ephaptic coupling plays a conduction-preserving role, particularly at rapid heart rates.

  13. Noise Gating Solar Images

    Science.gov (United States)

    DeForest, Craig; Seaton, Daniel B.; Darnell, John A.

    2017-08-01

    I present and demonstrate a new, general purpose post-processing technique, "3D noise gating", that can reduce image noise by an order of magnitude or more without effective loss of spatial or temporal resolution in typical solar applications.Nearly all scientific images are, ultimately, limited by noise. Noise can be direct Poisson "shot noise" from photon counting effects, or introduced by other means such as detector read noise. Noise is typically represented as a random variable (perhaps with location- or image-dependent characteristics) that is sampled once per pixel or once per resolution element of an image sequence. Noise limits many aspects of image analysis, including photometry, spatiotemporal resolution, feature identification, morphology extraction, and background modeling and separation.Identifying and separating noise from image signal is difficult. The common practice of blurring in space and/or time works because most image "signal" is concentrated in the low Fourier components of an image, while noise is evenly distributed. Blurring in space and/or time attenuates the high spatial and temporal frequencies, reducing noise at the expense of also attenuating image detail. Noise-gating exploits the same property -- "coherence" -- that we use to identify features in images, to separate image features from noise.Processing image sequences through 3-D noise gating results in spectacular (more than 10x) improvements in signal-to-noise ratio, while not blurring bright, resolved features in either space or time. This improves most types of image analysis, including feature identification, time sequence extraction, absolute and relative photometry (including differential emission measure analysis), feature tracking, computer vision, correlation tracking, background modeling, cross-scale analysis, visual display/presentation, and image compression.I will introduce noise gating, describe the method, and show examples from several instruments (including SDO

  14. A quantum Fredkin gate.

    Science.gov (United States)

    Patel, Raj B; Ho, Joseph; Ferreyrol, Franck; Ralph, Timothy C; Pryde, Geoff J

    2016-03-01

    Minimizing the resources required to build logic gates into useful processing circuits is key to realizing quantum computers. Although the salient features of a quantum computer have been shown in proof-of-principle experiments, difficulties in scaling quantum systems have made more complex operations intractable. This is exemplified in the classical Fredkin (controlled-SWAP) gate for which, despite theoretical proposals, no quantum analog has been realized. By adding control to the SWAP unitary, we use photonic qubit logic to demonstrate the first quantum Fredkin gate, which promises many applications in quantum information and measurement. We implement example algorithms and generate the highest-fidelity three-photon Greenberger-Horne-Zeilinger states to date. The technique we use allows one to add a control operation to a black-box unitary, something that is impossible in the standard circuit model. Our experiment represents the first use of this technique to control a two-qubit operation and paves the way for larger controlled circuits to be realized efficiently.

  15. Self-aligned local electrolyte gating of 2D materials with nanoscale resolution

    CERN Document Server

    Peng, Cheng; Nanot, Sebastien; Shiue, Ren-Jye; Grosso, Gabriele; Yang, Yafang; Hempel, Marek; Jarillo-Herrero, Pablo; Kong, Jing; Koppens, Frank H L; Englund, Dirk

    2016-01-01

    In the effort to make 2D materials-based devices smaller, faster, and more efficient, it is important to control charge carrier at lengths approaching the nanometer scale. Traditional gating techniques based on capacitive coupling through a gate dielectric cannot generate strong and uniform electric fields at this scale due to divergence of the fields in dielectrics. This field divergence limits the gating strength, boundary sharpness, and pitch size of periodic structures, and restricts possible geometries of local gates (due to wire packaging), precluding certain device concepts, such as plasmonics and transformation optics based on metamaterials. Here we present a new gating concept based on a dielectric-free self-aligned electrolyte technique that allows spatially modulating charges with nanometer resolution. We employ a combination of a solid-polymer electrolyte gate and an ion-impenetrable e-beam-defined resist mask to locally create excess charges on top of the gated surface. Electrostatic simulations ...

  16. Gated Si nanowires for large thermoelectric power factors

    Energy Technology Data Exchange (ETDEWEB)

    Neophytou, Neophytos, E-mail: N.Neophytou@warwick.ac.uk [School of Engineering, University of Warwick, Coventry CV4 7AL (United Kingdom); Kosina, Hans [Institute for Microelectronics, Vienna University of Technology, Gusshausstrasse 27-29/E360, Vienna A-1040 (Austria)

    2014-08-18

    We investigate the effect of electrostatic gating on the thermoelectric power factor of p-type Si nanowires (NWs) of up to 20 nm in diameter in the [100], [110], and [111] crystallographic transport orientations. We use atomistic tight-binding simulations for the calculation of the NW electronic structure, coupled to linearized Boltzmann transport equation for the calculation of the thermoelectric coefficients. We show that gated NW structures can provide ∼5× larger thermoelectric power factor compared to doped channels, attributed to their high hole phonon-limited mobility, as well as gating induced bandstructure modifications which further improve mobility. Despite the fact that gating shifts the charge carriers near the NW surface, surface roughness scattering is not strong enough to degrade the transport properties of the accumulated hole layer. The highest power factor is achieved for the [111] NW, followed by the [110], and finally by the [100] NW. As the NW diameter increases, the advantage of the gated channel is reduced. We show, however, that even at 20 nm diameters (the largest ones that we were able to simulate), a ∼3× higher power factor for gated channels is observed. Our simulations suggest that the advantage of gating could still be present in NWs with diameters of up to ∼40 nm.

  17. Impact of gate geometry on ionic liquid gated ionotronic systems

    Science.gov (United States)

    Wong, A. T.; Noh, J. H.; Pudasaini, P. R.; Wolf, B.; Balke, N.; Herklotz, A.; Sharma, Y.; Haglund, A. V.; Dai, S.; Mandrus, D.; Rack, P. D.; Ward, T. Z.

    2017-04-01

    Ionic liquid electrolytes are gaining widespread application as a gate dielectric used to control ion transport in functional materials. This letter systematically examines the important influence that device geometry in standard "side gate" 3-terminal geometries plays in device performance of a well-known oxygen ion conductor. We show that the most influential component of device design is the ratio between the area of the gate electrode and the active channel, while the spacing between these components and their individual shapes has a negligible contribution. These findings provide much needed guidance in device design intended for ionotronic gating with ionic liquids.

  18. Characterization of voltage-gated K+ currents contributing to subthreshold membrane potential oscillations in hippocampal CA1 interneurons.

    Science.gov (United States)

    Morin, France; Haufler, Darrell; Skinner, Frances K; Lacaille, Jean-Claude

    2010-06-01

    CA1 inhibitory interneurons at the stratum lacunosum-moleculare and radiatum junction (LM/RAD-INs) display subthreshold membrane potential oscillations (MPOs) involving voltage-dependent Na(+) and A-type K(+) currents. LM/RAD-INs also express other voltage-gated K(+) currents, although their properties and role in MPOs remain unclear. Here, we characterized these voltage-gated K(+) currents and investigated their role in MPOs. Using outside-out patch recordings from LM/RAD-IN somata, we distinguished four voltage-gated K(+) currents based on their pharmacology and activation/inactivation properties: a fast delayed rectifier current (I(Kfast)), a slow delayed rectifier current (I(Kslow)), a rapidly inactivating A-type current (I(A)), and a slowly inactivating current (I(D)). Their relative contribution to the total K(+) current was I(A) > I(Kfast) > I(Kslow) = I(D). The presence of I(D) and the relative contributions of K(+) currents in LM/RAD-INs are different from those of other CA1 interneurons, suggesting the presence of differential complement of K(+) currents in subgroups of interneurons. We next determined whether these K(+) currents were sufficient for MPO generation using a single-compartment model of LM/RAD-INs. The model captured the subthreshold voltage dependence of MPOs. Moreover, all K(+) currents were active at subthreshold potentials but I(D), I(A), and the persistent sodium current (I(NaP)) were most active near threshold. Using impedance analysis, we found that I(A) and I(NaP) contribute to MPO generation by modulating peak spectral frequency during MPOs and governing the voltage range over which MPOs occur. Our findings uncover a differential expression of a complement of K(+) channels that underlies intrinsic rhythmic activity in inhibitory interneurons.

  19. The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel

    Science.gov (United States)

    Marsakova, Lenka; Barvik, Ivan; Zima, Vlastimil; Zimova, Lucie; Vlachova, Viktorie

    2017-01-01

    Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works. Here we use molecular dynamics simulations combined with electrophysiological measurements and systematic mutagenesis to predict and explore the conformational changes coupled to the expansion of the presumptive channel's lower gate. We show that, upon opening, the upper part of the sensor module approaches the pore domain of an adjacent subunit and the conformational dynamics of the first extracellular flexible loop may govern the voltage-dependence of multimodal gating, thereby serving to stabilize the open state of the channel. These results are generally important in understanding the structure and function of TRPA1 and offer new insights into the gating mechanism of TRPA1 and related channels. PMID:28197074

  20. The impact of the C-terminal domain on the gating properties of MscCG from Corynebacterium glutamicum.

    Science.gov (United States)

    Nakayama, Yoshitaka; Becker, Michael; Ebrahimian, Haleh; Konishi, Tomoyuki; Kawasaki, Hisashi; Krämer, Reinhard; Martinac, Boris

    2016-01-01

    The mechanosensitive (MS) channel MscCG from the soil bacterium Corynebacterium glutamicum functions as a major glutamate exporter. MscCG belongs to a subfamily of the bacterial MscS-like channels, which play an important role in osmoregulation. To understand the structural and functional features of MscCG, we investigated the role of the carboxyl-terminal domain, whose relevance for the channel gating has been unknown. The chimeric channel MscS-(C-MscCG), which is a fusion protein between the carboxyl terminal domain of MscCG and the MscS channel, was examined by the patch clamp technique. We found that the chimeric channel exhibited MS channel activity in Escherichia coli spheroplasts characterized by a lower activation threshold and slow closing compared to MscS. The chimeric channel MscS-(C-MscCG) was successfully reconstituted into azolectin liposomes and exhibited gating hysteresis in a voltage-dependent manner, especially at high pipette voltages. Moreover, the channel remained open after releasing pipette pressure at membrane potentials physiologically relevant for C. glutamicum. This contribution to the gating hysteresis of the C-terminal domain of MscCG confers to the channel gating properties highly suitable for release of intracellular solutes.

  1. Gate complexity using Dynamic Programming

    OpenAIRE

    Sridharan, Srinivas; Gu, Mile; James, Matthew R.

    2008-01-01

    The relationship between efficient quantum gate synthesis and control theory has been a topic of interest in the quantum control literature. Motivated by this work, we describe in the present article how the dynamic programming technique from optimal control may be used for the optimal synthesis of quantum circuits. We demonstrate simulation results on an example system on SU(2), to obtain plots related to the gate complexity and sample paths for different logic gates.

  2. Localizing a gate in CFTR

    OpenAIRE

    Gao, Xiaolong; Hwang, Tzyh-Chang

    2015-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR), albeit a bona fide member of the ATP-binding cassette (ABC) transporter superfamily, is an ATP-gated chloride channel. However, phylogenetic analysis has led to a popular conjecture that CFTR evolves from a primordial ABC exporter by simply degenerating the cytoplasmic gate. This degraded transporter hypothesis predicts that CFTR’s gate is located at the external end of the substrate translocation pathway as the one documented in the...

  3. GATE TYPE SELECTION BASED ON FUZZY MAPPING

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Gate type selection is very important for mould design. Improper gate type may lead to poor product quality and low production efficiency. Although numerical simulation approach could be used to optimize gate location, the determination of gate type is still up to designers' experience. A novel method for selecting gate type based on fuzzy logic is proposed. The proposed methodology follows three steps:Design requirements for gate is extracted and generalized; Possible gate types (design schemes) are presented; The fuzzy mapping relationship between gate design requirements and gate design scheme is established based on fuzzy composition and fuzzy relation transition matrices that are assigned by domain experts.

  4. Expert Oracle GoldenGate

    CERN Document Server

    Prusinski, Ben; Chung, Richard

    2011-01-01

    Expert Oracle GoldenGate is a hands-on guide to creating and managing complex data replication environments using the latest in database replication technology from Oracle. GoldenGate is the future in replication technology from Oracle, and aims to be best-of-breed. GoldenGate supports homogeneous replication between Oracle databases. It supports heterogeneous replication involving other brands such as Microsoft SQL Server and IBM DB2 Universal Server. GoldenGate is high-speed, bidirectional, highly-parallelized, and makes only a light impact on the performance of databases involved in replica

  5. Genotypic to expression profiling of bovine calcium channel, voltage-dependent, alpha-2/delta subunit 1 gene, and their association with bovine mastitis among Frieswal (HFX Sahiwal) crossbred cattle of Indian origin.

    Science.gov (United States)

    Deb, Rajib; Singh, Umesh; Kumar, Sushil; Kumar, Arun; Singh, Rani; Sengar, Gyanendra; Mann, Sandeep; Sharma, Arjava

    2014-04-01

    Calcium channel, voltage-dependent, alpha-2/delta subunit 1 (CACNA2D1) gene is considered to be an important noncytokine candidate gene influencing mastitis. Scanty of reports are available until today regarding the role play of CACNA2D1 gene on the susceptibility of bovine mastitis. We interrogated the CACNA2D1 G519663A [A>G] SNP by PCR-RFLP among two hundreds Frieswal (HF X Sahiwal) crossbred cattle of Indian origin. Genotypic frequency of AA (51.5, n=101) was comparatively higher than AG (35, n=70) and GG (14.5, n=29). Association of Somatic cell score (SCS) with genotypes revealed that, GG genotypes showing lesser count (less susceptible to mastitis) compare to AA and AG. Relative expression of CACNA2D1 transcript (in milk samples) was significantly higher among GG than AG and AA. Further we have also isolated blood sample from the all groups and PBMCs were cultured from each blood sample as per the standard protocol. They were treated with Calcium channel blocker and the expression level of the CACNA2D1 gene was evaluated by Real Time PCR. Results show that expression level decline in each genotypic group after treatment and expression level of GG are again significantly higher than AA and AG. Thus, it may be concluded that GG genotypic animals are favorable for selecting disease resistant breeds.

  6. The Voltage-Dependent Anion Channel 1 (AtVDAC1 Negatively Regulates Plant Cold Responses during Germination and Seedling Development in Arabidopsis and Interacts with Calcium Sensor CBL1

    Directory of Open Access Journals (Sweden)

    Zhi-Yong Li

    2013-01-01

    Full Text Available The voltage-dependent anion channel (VDAC, a highly conserved major mitochondrial outer membrane protein, plays crucial roles in energy metabolism and metabolite transport. However, knowledge about the roles of the VDAC family in plants is limited. In this study, we investigated the expression pattern of VDAC1 in Arabidopsis and found that cold stress promoted the accumulation of VDAC1 transcripts in imbibed seeds and mature plants. Overexpression of VDAC1 reduced tolerance to cold stress in Arabidopsis. Phenotype analysis of VDAC1 T-DNA insertion mutant plants indicated that a vdac1 mutant line had faster germination kinetics under cold treatment and showed enhanced tolerance to freezing. The yeast two-hybrid system revealed that VDAC1 interacts with CBL1, a calcium sensor in plants. Like the vdac1, a cbl1 mutant also exhibited a higher seed germination rate. We conclude that both VDAC1 and CBL1 regulate cold stress responses during seed germination and plant development.

  7. Piezoconductivity of gated suspended graphene

    NARCIS (Netherlands)

    Medvedyeva, M.V.; Blanter, Y.M.

    2011-01-01

    We investigate the conductivity of graphene sheet deformed over a gate. The effect of the deformation on the conductivity is twofold: The lattice distortion can be represented as pseudovector potential in the Dirac equation formalism, whereas the gate causes inhomogeneous density redistribution. We

  8. Works close to gate B

    CERN Multimedia

    GS Department

    2011-01-01

    In connection to the TRAM project, drainage works will be carried out close to gate B until the end of next week. In order to avoid access problems, if arriving by car, please use gates A and E. Department of General Infrastructure Services (GS) GS-SE Group

  9. Cooperative gating between ion channels.

    Science.gov (United States)

    Choi, Kee-Hyun

    2014-01-01

    Cooperative gating between ion channels, i.e. the gating of one channel directly coupled to the gating of neighboring channels, has been observed in diverse channel types at the single-channel level. Positively coupled gating could enhance channel-mediated signaling while negative coupling may effectively reduce channel gating noise. Indeed, the physiological significance of cooperative channel gating in signal transduction has been recognized in several in vivo studies. Moreover, coupled gating of ion channels was reported to be associated with some human disease states. In this review, physiological roles for channel cooperativity and channel clustering observed in vitro and in vivo are introduced, and stimulation-induced channel clustering and direct channel cross linking are suggested as the physical mechanisms of channel assembly. Along with physical clustering, several molecular mechanisms proposed as the molecular basis for functional coupling of neighboring channels are covered: permeant ions as a channel coupling mediator, concerted channel activation through the membrane, and allosteric mechanisms. Also, single-channel analysis methods for cooperative gating such as the binomial analysis, the variance analysis, the conditional dwell time density analysis, and the maximum likelihood fitting analysis are reviewed and discussed.

  10. Penn State DOE GATE Program

    Energy Technology Data Exchange (ETDEWEB)

    Anstrom, Joel

    2012-08-31

    The Graduate Automotive Technology Education (GATE) Program at The Pennsylvania State University (Penn State) was established in October 1998 pursuant to an award from the U.S. Department of Energy (U.S. DOE). The focus area of the Penn State GATE Program is advanced energy storage systems for electric and hybrid vehicles.

  11. Logic Gates with Ion Transistors

    CERN Document Server

    Grebel, Haim

    2016-01-01

    Electronic logic gates are the basic building blocks of every computing and micro controlling system. Logic gates are made of switches, such as diodes and transistors. Ion-selective, ionic switches may emulate electronic switches [1-8]. If we ever want to create artificial bio-chemical circuitry, then we need to move a step further towards ion-logic circuitry. Here we demonstrate ion XOR and OR gates with electrochemical cells, and specifically, with two wet-cell batteries. In parallel to vacuum tubes, the batteries were modified to include a third, permeable and conductive mid electrode (the gate), which was placed between the anode and cathode in order to affect the ion flow through it. The key is to control the cell output with a much smaller biasing power, as demonstrated here. A successful demonstration points to self-powered ion logic gates.

  12. Entangling quantum gate in trapped ions via Rydberg blockade

    CERN Document Server

    Li, Weibin

    2013-01-01

    We present a theoretical analysis of the implementation of an entangling quantum gate between two trapped Ca$^+$ ions which is based on the dipolar interaction among ionic Rydberg states. In trapped ions the Rydberg excitation dynamics is usually strongly affected by mechanical forces due to the strong couplings between electronic and vibrational degrees of freedom in inhomogeneous electric fields. We demonstrate that this harmful effect can be overcome by using dressed states that emerge from the microwave coupling of nearby Rydberg states. At the same time these dressed states exhibit long range dipolar interactions which we use to implement a controlled adiabatic phase gate. Our study highlights a route towards a trapped ion quantum processor in which quantum gates are realized independently of the vibrational modes.

  13. Gate Stack Engineering and Thermal Treatment on Electrical and Interfacial Properties of Ti/Pt/HfO2/InAs pMOS Capacitors

    Directory of Open Access Journals (Sweden)

    Chung-Yen Chien

    2012-01-01

    Full Text Available Effects of gate stack engineering and thermal treatment on electrical and interfacial properties of Ti/Pt/HfO2/InAs metal insulator semiconductor (MIS capacitors were systematically evaluated in terms of transmission electron microscopy, energy dispersive X-ray spectroscopy, current-voltage, and capacitance-voltage characterizations. A 10 nm thick Pt metal effectively suppresses the formation of interfacial oxide, TiO2, between the Ti gate and HfO2 gate dielectric layer, enhancing the gate modulation on the surface potential of InAs. An in situ HfO2 deposition onto the n-InAs channel with an interfacial layer (IL of one-monolayer InP followed by a 300°C post-metal-anneal produces a high-quality HfO2/InAs interface and thus unravels the annoying Fermi-level pinning, which is evidenced by the distinct capacitance dips in the high-/low-frequency C-V characteristics. The interface trap states could be further suppressed by replacing the InP IL by an As-rich InAs, which is substantiated by a gate leakage reduction and a steep voltage-dependent depletion capacitance.

  14. Towards an experimentally feasible controlled-phase gate on two blockaded Rydberg atoms

    CERN Document Server

    Murphy, Michael; Calarco, Tommaso; Grangier, Philippe; Browaeys, Antoine

    2011-01-01

    We investigate the implementation of a controlled-Z gate on a pair of Rydberg atoms in spatially separated dipole traps where the joint excitation of both atoms into the Rydberg level is strongly suppressed (the Rydberg blockade). We follow the adiabatic gate scheme of Jaksch et al. [1], where the pair of atoms are coherently excited using lasers, and apply it to the experimental setup outlined in Ga\\"etan et al. [2]. We apply optimisation to the experimental parameters to improve gate fidelity, and consider the impact of several experimental constraints on the gate success.

  15. Switching terahertz waves with gate-controlled active graphene metamaterials.

    Science.gov (United States)

    Lee, Seung Hoon; Choi, Muhan; Kim, Teun-Teun; Lee, Seungwoo; Liu, Ming; Yin, Xiaobo; Choi, Hong Kyw; Lee, Seung S; Choi, Choon-Gi; Choi, Sung-Yool; Zhang, Xiang; Min, Bumki

    2012-11-01

    The extraordinary electronic properties of graphene provided the main thrusts for the rapid advance of graphene electronics. In photonics, the gate-controllable electronic properties of graphene provide a route to efficiently manipulate the interaction of photons with graphene, which has recently sparked keen interest in graphene plasmonics. However, the electro-optic tuning capability of unpatterned graphene alone is still not strong enough for practical optoelectronic applications owing to its non-resonant Drude-like behaviour. Here, we demonstrate that substantial gate-induced persistent switching and linear modulation of terahertz waves can be achieved in a two-dimensional metamaterial, into which an atomically thin, gated two-dimensional graphene layer is integrated. The gate-controllable light-matter interaction in the graphene layer can be greatly enhanced by the strong resonances of the metamaterial. Although the thickness of the embedded single-layer graphene is more than six orders of magnitude smaller than the wavelength (metamaterial, can modulate both the amplitude of the transmitted wave by up to 47% and its phase by 32.2° at room temperature. More interestingly, the gate-controlled active graphene metamaterials show hysteretic behaviour in the transmission of terahertz waves, which is indicative of persistent photonic memory effects.

  16. Regulatory role of voltage-gated sodium channel β subunits in sensory neurons

    Directory of Open Access Journals (Sweden)

    Mohamed eChahine

    2011-11-01

    Full Text Available Voltage-gated Na+ channels are transmembrane-bound proteins incorporating aqueous conduction pores that are highly selective for Na+. The opening of these channels results in the rapid influx of Na+ ions that depolarize the cell and drive the rapid upstroke of nerve and muscle action potentials. While the concept of a Na+-selective ion channel had been formulated in the 1940s, it was not until the 1980s that the biochemical properties of the 260-kDa and 36-kDa auxiliary β subunits (β1, β2 were first described. Subsequent cloning and heterologous expression studies revealed that the  subunit forms the core of the channel and is responsible for both voltage-dependent gating and ionic selectivity. To date, ten isoforms of the Na+ channel α subunit have been identified that vary in their primary structures, tissue distribution, biophysical properties, and sensitivity to neurotoxins. Four β subunits (β1-β4 and two splice variants (β1A, β1B have been identified that modulate the subcellular distribution, cell surface expression, and functional properties of the α subunits. The purpose of this review is to provide a broad overview of β subunit expression and function in peripheral sensory neurons and examine their contributions to neuropathic pain.

  17. PROPERTIES OF VOLTAGE-GATED SODIUM CHANNELS IN DEVELOPING AUDITORY NEURONS OF THE MOUSE IN VITRO

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective. To investigate the properties of voltage-gated sodium (Na+) channels in developing auditoryneurons during early postnatal stages in the mammalian central nervous system.Methods. Using the whole-cell voltage-clamp technique, we have studied changes in the electrophysi-ological properties of Na+ channels in the principal neurons of the medial nucleus of the trapezoid body (MNTB).Results. We found that MNTB neurons already express functional Na+ channels at postnatal day 1 (P1),and that channel density begins to increase at P5 when the neurons receive synaptic innervation andreach its maximum (~3 fold) at P11 when functional hearing onsets. These changes were paralleled byan age-dependent acceleration in both inactivation and recovery from inactivation. In contrast, there wasvery little alteration in the voltage-dependence of inactivation.Conclusion. These profound changes in the properties of voltage-gated Na+ channels may increase theexcitability of MNTB neurons and enhance their phase-locking fidelity and capacity during high-frequencysynaptic transmission.

  18. Modification of sodium and potassium channel gating kinetics by ether and halothane

    Energy Technology Data Exchange (ETDEWEB)

    Bean, B.P.; Shrager, P.; Goldstein, D.A.

    1981-03-01

    The effects of ether and halothane on the kinetics of sodium and potassium currents were investigated in the crayfish giant axon. Both general anesthetics produced a reversible, dose-dependent speeding up of sodium current inactivation at all membrane potentials, with no change in the rising phase of the currents. Double-pulse inactivation experiments with ether also showed faster inactivation, but the rate of recovery from inactivation at negative potentials was not affected. Ether shifted the midpoint of the steady-state fast inactivation curve in the hyperpolarizing direction and made the curve steeper. The activation of potassium currents was faster with ether present, with no change in the voltage dependence of steady-state potassium currents. Ether and halothane are known to perturb the structure of lipid bilayer membranes; the alterations in sodium and potassium channel gating kinetics are consistent with the hypothesis that the rats of the gating processes of the channels can be affected by the state of the lipids surrounding the channels, but a direct effect of ether and halothane on the protein part of the channels cannot be ruled out.

  19. Voltage-gated proton (H(v)1) channels, a singular voltage sensing domain.

    Science.gov (United States)

    Castillo, Karen; Pupo, Amaury; Baez-Nieto, David; Contreras, Gustavo F; Morera, Francisco J; Neely, Alan; Latorre, Ramon; Gonzalez, Carlos

    2015-11-14

    The main role of voltage-gated proton channels (Hv1) is to extrude protons from the intracellular milieu when, mediated by different cellular processes, the H(+) concentration increases. Hv1 are exquisitely selective for protons and their structure is homologous to the voltage sensing domain (VSD) of other voltage-gated ion channels like sodium, potassium, and calcium channels. In clear contrast to the classical voltage-dependent channels, Hv1 lacks a pore domain and thus permeation necessarily occurs through the voltage sensing domain. Hv1 channels are activated by depolarizing voltages, and increases in internal proton concentration. It has been proposed that local conformational changes of the transmembrane segment S4, driven by depolarization, trigger the molecular rearrangements that open Hv1. However, it is still unclear how the electromechanical coupling is achieved between the VSD and the potential pore, allowing the proton flux from the intracellular to the extracellular side. Here we provide a revised view of voltage activation in Hv1 channels, offering a comparative scenario with other voltage sensing channels domains.

  20. Comprehensive behavioral model of dual-gate high voltage JFET and pinch resistor

    Science.gov (United States)

    Banáš, Stanislav; Paňko, Václav; Dobeš, Josef; Hanyš, Petr; Divín, Jan

    2016-09-01

    Many analog technologies operate in large voltage range and therefore include at least one or more high voltage devices built from low doped layers. Such devices exhibit effects not covered by standard compact models, namely pinching (depletion) effects, in high voltage FETs often called quasisaturation. For example, the conventional compact JFET model is insufficient and oversimplified. Its scalability is controlled by the area factor, which only multiplies currents and capacitances but does not take into account existing 3-D effects. Also the optional second independent gate is missing. Therefore, the customized four terminal (4T) model written in Verilog-A (FitzPatrick and Miller, 2007; Sagdeo, 2007) was developed. It converges very well, its simulation speed is comparable with conventional compact models, and contains all required phenomena, including parasitic effects as, for example, impact ionization. This model has universal usage for many types of devices in various high voltage technologies such as stand-alone voltage dependent resistor, pinch resistor, drift area of power FET, part of special high side or start-up devices, and dual-gate JFET.

  1. Calmodulin is essential for cardiac IKS channel gating and assembly: impaired function in long-QT mutations

    DEFF Research Database (Denmark)

    Shamgar, Liora; Ma, Lijuan; Schmitt, Nicole;

    2006-01-01

    The slow IKS K+ channel plays a major role in repolarizing the cardiac action potential and consists of the assembly of KCNQ1 and KCNE1 subunits. Mutations in either KCNQ1 or KCNE1 genes produce the long-QT syndrome, a life-threatening ventricular arrhythmia. Here, we show that long-QT mutations...... located in the KCNQ1 C terminus impair calmodulin (CaM) binding, which affects both channel gating and assembly. The mutations produce a voltage-dependent macroscopic inactivation and dramatically alter channel assembly. KCNE1 forms a ternary complex with wild-type KCNQ1 and Ca(2+)-CaM that prevents...... the risk of ventricular arrhythmias. Udgivelsesdato: 2006-Apr-28...

  2. A circuit QED controlled-Z ``AMP'' gate (Adiabatic MultiPole gate)

    Science.gov (United States)

    McKay, David C.; Naik, Ravi; Bishop, Lev S.; Schuster, David I.

    2014-03-01

    Circuit quantum electrodynamics -- superconducting Josephson junction ``transmon'' qubits coupled via microwave cavities -- is a promising route towards scalable quantum computing. Here we report on experiments coupling two transmon qubits through multiple strongly coupled planar superconducting cavities -- the multipole cavity QED architecture. This design enables large interactions (mediated by real cavity photons) when the transmons are resonant with the cavities, and low off rates when the qubits are tuned away from the cavity resonance. In this talk we will discuss our gate protocol -- the AMP gate -- and report on producing a high fidelity Bell state (| gg > + | ee >) measured from state and process tomography. We will discuss future plans for scaling this architecture beyond two qubits.

  3. Reversible logic gates on Physarum Polycephalum

    Energy Technology Data Exchange (ETDEWEB)

    Schumann, Andrew [University of Information Technology and Management, Sucharskiego 2, Rzeszow, 35-225 (Poland)

    2015-03-10

    In this paper, we consider possibilities how to implement asynchronous sequential logic gates and quantum-style reversible logic gates on Physarum polycephalum motions. We show that in asynchronous sequential logic gates we can erase information because of uncertainty in the direction of plasmodium propagation. Therefore quantum-style reversible logic gates are more preferable for designing logic circuits on Physarum polycephalum.

  4. Demonstration of a Quantum Nondemolition Sum Gate

    DEFF Research Database (Denmark)

    Yoshikawa, J.; Miwa, Y.; Huck, Alexander;

    2008-01-01

    The sum gate is the canonical two-mode gate for universal quantum computation based on continuous quantum variables. It represents the natural analogue to a qubit C-NOT gate. In addition, the continuous-variable gate describes a quantum nondemolition (QND) interaction between the quadrature compo...

  5. The insecticidal neurotoxin Aps III is an atypical knottin peptide that potently blocks insect voltage-gated sodium channels.

    Science.gov (United States)

    Bende, Niraj S; Kang, Eunji; Herzig, Volker; Bosmans, Frank; Nicholson, Graham M; Mobli, Mehdi; King, Glenn F

    2013-05-15

    One of the most potent insecticidal venom peptides described to date is Aps III from the venom of the trapdoor spider Apomastus schlingeri. Aps III is highly neurotoxic to lepidopteran crop pests, making it a promising candidate for bioinsecticide development. However, its disulfide-connectivity, three-dimensional structure, and mode of action have not been determined. Here we show that recombinant Aps III (rAps III) is an atypical knottin peptide; three of the disulfide bridges form a classical inhibitor cystine knot motif while the fourth disulfide acts as a molecular staple that restricts the flexibility of an unusually large β hairpin loop that often houses the pharmacophore in this class of toxins. We demonstrate that the irreversible paralysis induced in insects by rAps III results from a potent block of insect voltage-gated sodium channels. Channel block by rAps III is voltage-independent insofar as it occurs without significant alteration in the voltage-dependence of channel activation or steady-state inactivation. Thus, rAps III appears to be a pore blocker that plugs the outer vestibule of insect voltage-gated sodium channels. This mechanism of action contrasts strikingly with virtually all other sodium channel modulators isolated from spider venoms that act as gating modifiers by interacting with one or more of the four voltage-sensing domains of the channel. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Randomized benchmarking of multiqubit gates.

    Science.gov (United States)

    Gaebler, J P; Meier, A M; Tan, T R; Bowler, R; Lin, Y; Hanneke, D; Jost, J D; Home, J P; Knill, E; Leibfried, D; Wineland, D J

    2012-06-29

    We describe an extension of single-qubit gate randomized benchmarking that measures the error of multiqubit gates in a quantum information processor. This platform-independent protocol evaluates the performance of Clifford unitaries, which form a basis of fault-tolerant quantum computing. We implemented the benchmarking protocol with trapped ions and found an error per random two-qubit Clifford unitary of 0.162±0.008, thus setting the first benchmark for such unitaries. By implementing a second set of sequences with an extra two-qubit phase gate inserted after each step, we extracted an error per phase gate of 0.069±0.017. We conducted these experiments with transported, sympathetically cooled ions in a multizone Paul trap-a system that can in principle be scaled to larger numbers of ions.

  7. Bill Gates vil redde Folkeskolen

    DEFF Research Database (Denmark)

    Fejerskov, Adam Moe

    2014-01-01

    Det amerikanske uddannelsessystem bliver for tiden udsat for hård kritik, ledt an af Microsoft stifteren Bill Gates. Gates har indtil videre brugt 3 mia. kroner på at skabe opbakning til tiltag som præstationslønning af lærere og strømlining af pensum på tværs af alle skoler i landet......Det amerikanske uddannelsessystem bliver for tiden udsat for hård kritik, ledt an af Microsoft stifteren Bill Gates. Gates har indtil videre brugt 3 mia. kroner på at skabe opbakning til tiltag som præstationslønning af lærere og strømlining af pensum på tværs af alle skoler i landet...

  8. Back-gate effects and mobility characterization in junctionless transistor

    Science.gov (United States)

    Parihar, Mukta Singh; Liu, Fanyu; Navarro, Carlos; Barraud, Sylvain; Bawedin, Maryline; Ionica, Irina; Kranti, Abhinav; Cristoloveanu, Sorin

    2016-11-01

    This work addresses the effect of inter-gate coupling on back-channel characteristics of planar accumulation-mode junctionless (JL) MOSFETs, fabricated with advanced Fully Depleted Silicon-on-Insulator (FDSOI) technology. A systematic methodology to extract and distinguish the contributions of bulk and accumulation-mode mobility has been developed. Front-gate voltage strongly controls the transport properties of back channel in ultra-thin heavily doped JL devices. It is demonstrated that both volume and accumulation-layer mobility values increase when the front interface is in accumulation.

  9. Bill Gates vil redde Folkeskolen

    DEFF Research Database (Denmark)

    Fejerskov, Adam Moe

    2014-01-01

    Det amerikanske uddannelsessystem bliver for tiden udsat for hård kritik, ledt an af Microsoft stifteren Bill Gates. Gates har indtil videre brugt 3 mia. kroner på at skabe opbakning til tiltag som præstationslønning af lærere og strømlining af pensum på tværs af alle skoler i landet...

  10. Quantum gates with topological phases

    CERN Document Server

    Ionicioiu, R

    2003-01-01

    We investigate two models for performing topological quantum gates with the Aharonov-Bohm (AB) and Aharonov-Casher (AC) effects. Topological one- and two-qubit Abelian phases can be enacted with the AB effect using charge qubits, whereas the AC effect can be used to perform all single-qubit gates (Abelian and non-Abelian) for spin qubits. Possible experimental setups suitable for a solid state implementation are briefly discussed.

  11. Gating a ferromagnetic semiconductor

    Science.gov (United States)

    Bove, A.; Altomare, F.; Kundtz, N.; Chang, A. M.; Cho, Y. J.; Liu, X.; Furdyna, J.

    2007-03-01

    Ferromagnetic semiconductors have the potential of revolutionizing the way current electronic devices work: more so, because they are compatible with current fabrication lines and can easily be integrated with today's technology. Particular interest lies in III-V Diluted Magnetic Semiconductor (DMS), where the ferromagnetism is hole-mediated and the Curie temperature can therefore be tuned by changing the concentration of free carriers. In these systems, most of the effort is currently applied toward the fabrication of devices working at room-temperature: this implies high carrier density accompanied by low mobility and short mean free path. We will report our results for a ferromagnetic 2DHG system with low carrier density (˜3.4E12 cm-2) and mobility (˜ 1000 cm^2/(Vs)), and we will discuss the effects of local gating in light of possible applications to the fabrication of ferromagnetic quantum dots. T. Dietl et al., Phys. Rev. B 63, 195205 (2001). H. Ohno et al., Nature 408, 944 (2000)

  12. Latest design of gate valves

    Energy Technology Data Exchange (ETDEWEB)

    Kurzhofer, U.; Stolte, J.; Weyand, M.

    1996-12-01

    Babcock Sempell, one of the most important valve manufacturers in Europe, has delivered valves for the nuclear power industry since the beginning of the peaceful application of nuclear power in the 1960s. The latest innovation by Babcock Sempell is a gate valve that meets all recent technical requirements of the nuclear power technology. At the moment in the United States, Germany, Sweden, and many other countries, motor-operated gate and globe valves are judged very critically. Besides the absolute control of the so-called {open_quotes}trip failure,{close_quotes} the integrity of all valve parts submitted to operational forces must be maintained. In case of failure of the limit and torque switches, all valve designs have been tested with respect to the quality of guidance of the gate. The guidances (i.e., guides) shall avoid a tilting of the gate during the closing procedure. The gate valve newly designed by Babcock Sempell fulfills all these characteristic criteria. In addition, the valve has cobalt-free seat hardfacing, the suitability of which has been proven by friction tests as well as full-scale blowdown tests at the GAP of Siemens in Karlstein, West Germany. Babcock Sempell was to deliver more than 30 gate valves of this type for 5 Swedish nuclear power stations by autumn 1995. In the presentation, the author will report on the testing performed, qualifications, and sizing criteria which led to the new technical design.

  13. Robustness against parametric noise of non ideal holonomic gates

    CERN Document Server

    Lupo, C; Florio, G; Napolitano, M; Aniello, Paolo; Florio, Giuseppe; Lupo, Cosmo; Napolitano, Mario

    2006-01-01

    Holonomic gates for quantum computation are commonly considered to be robust against certain kinds of parametric noise, the very motivation for this robustness being the geometric character of the transformation achieved in the adiabatic limit. On the other hand, the effects of decoherence are expected to become more and more relevant when the adiabatic limit is approached. Starting from the system described by Florio et al. [Phys. Rev. A 73, 022327 (2006)], here we discuss the behavior of non ideal holonomic gates at finite operational time, i.e., far before the adiabatic limit is reached. We have considered several models of parametric noise and studied the robustness of finite time gates. The main result is that the issue of robustness is problematic and may strongly depend on some features of the noise such as its symmetries and typical frequencies.

  14. Electrolyte-Gated Graphene Ambipolar Frequency Multipliers for Biochemical Sensing.

    Science.gov (United States)

    Fu, Wangyang; Feng, Lingyan; Mayer, Dirk; Panaitov, Gregory; Kireev, Dmitry; Offenhäusser, Andreas; Krause, Hans-Joachim

    2016-04-13

    In this Letter, the ambipolar properties of an electrolyte-gated graphene field-effect transistor (GFET) have been explored to fabricate frequency-doubling biochemical sensor devices. By biasing the ambipolar GFETs in a common-source configuration, an input sinusoidal voltage at frequency f applied to the electrolyte gate can be rectified to a sinusoidal wave at frequency 2f at the drain electrode. The extraordinary high carrier mobility of graphene and the strong electrolyte gate coupling provide the graphene ambipolar frequency doubler an unprecedented unity gain, as well as a detection limit of ∼4 pM for 11-mer single strand DNA molecules in 1 mM PBS buffer solution. Combined with an improved drift characteristics and an enhanced low-frequency 1/f noise performance by sampling at doubled frequency, this good detection limit suggests the graphene ambipolar frequency doubler a highly promising biochemical sensing platform.

  15. Dynamic Partitioning of GATE Monte-Carlo Simulations on EGEE

    CERN Document Server

    Camarasu-Pop, S; Benoit-Cattin, Hugues; Glatard, Tristan; Sarrut, David; Camarasu-Pop, Sorina

    2010-01-01

    The EGEE Grid offers the necessary infrastructure and resources for reducing the running time of particle tracking Monte-Carlo applications like GATE. However, efforts are required to achieve reliable and efficient execution and to provide execution frameworks to end-users. This paper presents results obtained with porting the GATE software on the EGEE Grid, our ultimate goal being to provide reliable, user-friendly and fast execution of GATE to radiation therapy researchers. To address these requirements, we propose a new parallelization scheme based on a dynamic partitioning and its implementation in two different frameworks using pilot jobs and workflows. Results show that pilot jobs bring strong improvement w.r.t. regular gLite submission, that the proposed dynamic partitioning algorithm further reduces execution time by a factor of two and that the genericity and user-friendliness offered by the workflow implementation do not introduce significant overhead.

  16. Desensitization mechanism in prokaryotic ligand-gated ion channel.

    Science.gov (United States)

    Velisetty, Phanindra; Chakrapani, Sudha

    2012-05-25

    Crystal structures of Gloeobacter violaceus ligand-gated ion channel (GLIC), a proton-gated prokaryotic homologue of pentameric ligand-gated ion channel (LGIC) from G. violaceus, have provided high-resolution models of the channel architecture and its role in selective ion conduction and drug binding. However, it is still unclear which functional states of the LGIC gating scheme these crystal structures represent. Much of this uncertainty arises from a lack of thorough understanding of the functional properties of these prokaryotic channels. To elucidate the molecular events that constitute gating, we have carried out an extensive characterization of GLIC function and dynamics in reconstituted proteoliposomes by patch clamp measurements and EPR spectroscopy. We find that GLIC channels show rapid activation upon jumps to acidic pH followed by a time-dependent loss of conductance because of desensitization. GLIC desensitization is strongly coupled to activation and is modulated by voltage, permeant ions, pore-blocking drugs, and membrane cholesterol. Many of these properties are parallel to functions observed in members of eukaryotic LGIC. Conformational changes in loop C, measured by site-directed spin labeling and EPR spectroscopy, reveal immobilization during desensitization analogous to changes in LGIC and acetylcholine binding protein. Together, our studies suggest conservation of mechanistic aspects of desensitization among LGICs of prokaryotic and eukaryotic origin.

  17. Transparent conducting oxide induced by liquid electrolyte gating

    Science.gov (United States)

    ViolBarbosa, Carlos; Karel, Julie; Kiss, Janos; Gordan, Ovidiu-dorin; Altendorf, Simone G.; Utsumi, Yuki; Samant, Mahesh G.; Wu, Yu-Han; Tsuei, Ku-Ding; Felser, Claudia; Parkin, Stuart S. P.

    2016-10-01

    Optically transparent conducting materials are essential in modern technology. These materials are used as electrodes in displays, photovoltaic cells, and touchscreens; they are also used in energy-conserving windows to reflect the infrared spectrum. The most ubiquitous transparent conducting material is tin-doped indium oxide (ITO), a wide-gap oxide whose conductivity is ascribed to n-type chemical doping. Recently, it has been shown that ionic liquid gating can induce a reversible, nonvolatile metallic phase in initially insulating films of WO3. Here, we use hard X-ray photoelectron spectroscopy and spectroscopic ellipsometry to show that the metallic phase produced by the electrolyte gating does not result from a significant change in the bandgap but rather originates from new in-gap states. These states produce strong absorption below ˜1 eV, outside the visible spectrum, consistent with the formation of a narrow electronic conduction band. Thus WO3 is metallic but remains colorless, unlike other methods to realize tunable electrical conductivity in this material. Core-level photoemission spectra show that the gating reversibly modifies the atomic coordination of W and O atoms without a substantial change of the stoichiometry; we propose a simple model relating these structural changes to the modifications in the electronic structure. Thus we show that ionic liquid gating can tune the conductivity over orders of magnitude while maintaining transparency in the visible range, suggesting the use of ionic liquid gating for many applications.

  18. Use of the GATE Monte Carlo package for dosimetry applications

    Energy Technology Data Exchange (ETDEWEB)

    Visvikis, D. [INSERM U650, LaTIM, University Hospital Medical School, F 29609 Brest (France)]. E-mail: Visvikis.Dimitris@univ-brest.fr; Bardies, M. [INSERM U601, CHU Nantes, F 44093 Nantes (France); Chiavassa, S. [INSERM U601, CHU Nantes, F 44093 Nantes (France); Danford, C. [Department of Medical Physics, MSKCC, New York (United States); Kirov, A. [Department of Medical Physics, MSKCC, New York (United States); Lamare, F. [INSERM U650, LaTIM, University Hospital Medical School, F 29609 Brest (France); Maigne, L. [Departement de Curietherapie-Radiotherapie, Centre Jean Perrin, F 63000 Clemont-Ferrand (France); Staelens, S. [UGent-ELIS, St-Pietersnieuwstraat, 41, B 9000 Gent (Belgium); Taschereau, R. [CRUMP Institute for Molecular Imaging, UCLA, Los Angeles (United States)

    2006-12-20

    One of the roles for Monte Carlo (MC) simulation studies is in the area of dosimetry. A number of different codes dedicated to dosimetry applications are available and widely used today, such as MCNP, EGSnrc and PTRAN. However, such codes do not easily facilitate the description of complicated 3D sources or emission tomography systems and associated data flow, which may be useful in different dosimetry application domains. Such problems can be overcome by the use of specific MC codes such as GATE (GEANT4 Application to Tomographic Emission), which is based on Geant4 libraries, providing a scripting interface with a number of advantages for the simulation of SPECT and PET systems. Despite this potential, its major disadvantage is in terms of efficiency involving long execution times for applications such as dosimetry. The strong points and disadvantages of GATE in comparison to other dosimetry specific codes are discussed and illustrated in terms of accuracy, efficiency and flexibility. A number of features, such as the use of voxelised and moving sources, as well as developments such as advanced visualization tools and the development of dose estimation maps allowing GATE to be used for dosimetry applications are presented. In addition, different examples from dosimetry applications with GATE are given. Finally, future directions with respect to the use of GATE for dosimetry applications are outlined.

  19. New opening hours of the gates

    CERN Multimedia

    GS Department

    2009-01-01

    Please note the new opening hours of the gates as well as the intersites tunnel from the 19 May 2009: GATE A 7h - 19h GATE B 24h/24 GATE C 7h - 9h\t17h - 19h GATE D 8h - 12h\t13h - 16h GATE E 7h - 9h\t17h - 19h Prévessin 24h/24 The intersites tunnel will be opened from 7h30 to 18h non stop. GS-SEM Group Infrastructure and General Services Department

  20. Ionic thermoelectric gating organic transistors

    Science.gov (United States)

    Zhao, Dan; Fabiano, Simone; Berggren, Magnus; Crispin, Xavier

    2017-01-01

    Temperature is one of the most important environmental stimuli to record and amplify. While traditional thermoelectric materials are attractive for temperature/heat flow sensing applications, their sensitivity is limited by their low Seebeck coefficient (∼100 μV K−1). Here we take advantage of the large ionic thermoelectric Seebeck coefficient found in polymer electrolytes (∼10,000 μV K−1) to introduce the concept of ionic thermoelectric gating a low-voltage organic transistor. The temperature sensing amplification of such ionic thermoelectric-gated devices is thousands of times superior to that of a single thermoelectric leg in traditional thermopiles. This suggests that ionic thermoelectric sensors offer a way to go beyond the limitations of traditional thermopiles and pyroelectric detectors. These findings pave the way for new infrared-gated electronic circuits with potential applications in photonics, thermography and electronic-skins. PMID:28139738

  1. Ionic thermoelectric gating organic transistors

    Science.gov (United States)

    Zhao, Dan; Fabiano, Simone; Berggren, Magnus; Crispin, Xavier

    2017-01-01

    Temperature is one of the most important environmental stimuli to record and amplify. While traditional thermoelectric materials are attractive for temperature/heat flow sensing applications, their sensitivity is limited by their low Seebeck coefficient (~100 μV K-1). Here we take advantage of the large ionic thermoelectric Seebeck coefficient found in polymer electrolytes (~10,000 μV K-1) to introduce the concept of ionic thermoelectric gating a low-voltage organic transistor. The temperature sensing amplification of such ionic thermoelectric-gated devices is thousands of times superior to that of a single thermoelectric leg in traditional thermopiles. This suggests that ionic thermoelectric sensors offer a way to go beyond the limitations of traditional thermopiles and pyroelectric detectors. These findings pave the way for new infrared-gated electronic circuits with potential applications in photonics, thermography and electronic-skins.

  2. Localizing a gate in CFTR.

    Science.gov (United States)

    Gao, Xiaolong; Hwang, Tzyh-Chang

    2015-02-24

    Experimental and computational studies have painted a picture of the chloride permeation pathway in cystic fibrosis transmembrane conductance regulator (CFTR) as a short narrow tunnel flanked by wider inner and outer vestibules. Although these studies also identified a number of transmembrane segments (TMs) as pore-lining, the exact location of CFTR's gate(s) remains unknown. Here, using a channel-permeant probe, [Au(CN)2](-), we provide evidence that CFTR bears a gate that coincides with the predicted narrow section of the pore defined as residues 338-341 in TM6. Specifically, cysteines introduced cytoplasmic to the narrow region (i.e., positions 344 in TM6 and 1148 in TM12) can be modified by intracellular [Au(CN)2](-) in both open and closed states, corroborating the conclusion that the internal vestibule does not harbor a gate. However, cysteines engineered to positions external to the presumed narrow region (e.g., 334, 335, and 337 in TM6) are all nonreactive toward cytoplasmic [Au(CN)2](-) in the absence of ATP, whereas they can be better accessed by extracellular [Au(CN)2](-) when the open probability is markedly reduced by introducing a second mutation, G1349D. As [Au(CN)2](-) and chloride ions share the same permeation pathway, these results imply a gate is situated between amino acid residues 337 and 344 along TM6, encompassing the very segment that may also serve as the selectivity filter for CFTR. The unique position of a gate in the middle of the ion translocation pathway diverges from those seen in ATP-binding cassette (ABC) transporters and thus distinguishes CFTR from other members of the ABC transporter family.

  3. Respiratory gating in cardiac PET

    DEFF Research Database (Denmark)

    Lassen, Martin Lyngby; Rasmussen, Thomas; Christensen, Thomas E

    2017-01-01

    BACKGROUND: Respiratory motion due to breathing during cardiac positron emission tomography (PET) results in spatial blurring and erroneous tracer quantification. Respiratory gating might represent a solution by dividing the PET coincidence dataset into smaller respiratory phase subsets. The aim...... stress (82)RB-PET. Respiratory rates and depths were measured by a respiratory gating system in addition to registering actual respiratory rates. Patients undergoing adenosine stress showed a decrease in measured respiratory rate from initial to later scan phase measurements [12.4 (±5.7) vs 5.6 (±4.......7) min(-1), P PET...

  4. Alcohol modulation of BK channel gating depends on β subunit composition.

    Science.gov (United States)

    Kuntamallappanavar, Guruprasad; Dopico, Alex M

    2016-11-01

    In most mammalian tissues, Ca(2+)i/voltage-gated, large conductance K(+) (BK) channels consist of channel-forming slo1 and auxiliary (β1-β4) subunits. When Ca(2+)i (3-20 µM) reaches the vicinity of BK channels and increases their activity at physiological voltages, β1- and β4-containing BK channels are, respectively, inhibited and potentiated by intoxicating levels of ethanol (50 mM). Previous studies using different slo1s, lipid environments, and Ca(2+)i concentrations-all determinants of the BK response to ethanol-made it impossible to determine the specific contribution of β subunits to ethanol action on BK activity. Furthermore, these studies measured ethanol action on ionic current under a limited range of stimuli, rendering no information on the gating processes targeted by alcohol and their regulation by βs. Here, we used identical experimental conditions to obtain single-channel and macroscopic currents of the same slo1 channel ("cbv1" from rat cerebral artery myocytes) in the presence and absence of 50 mM ethanol. First, we assessed the role five different β subunits (1,2,2-IR, 3-variant d, and 4) in ethanol action on channel function. Thus, two phenotypes were identified: (1) ethanol potentiated cbv1-, cbv1+β3-, and cbv1+β4-mediated currents at low Ca(2+)i while inhibiting current at high Ca(2+)i, the potentiation-inhibition crossover occurring at 20 µM Ca(2+)i; (2) for cbv1+β1, cbv1+wt β2, and cbv1+β2-IR, this crossover was shifted to ∼3 µM Ca(2+)i Second, applying Horrigan-Aldrich gating analysis on both phenotypes, we show that ethanol fails to modify intrinsic gating and the voltage-dependent parameters under examination. For cbv1, however, ethanol (a) drastically increases the channel's apparent Ca(2+) affinity (nine-times decrease in Kd) and (b) very mildly decreases allosteric coupling between Ca(2+) binding and channel opening (C). The decreased Kd leads to increased channel activity. For cbv1+β1, ethanol (a) also decreases Kd

  5. Reversible logic gate using adiabatic superconducting devices

    National Research Council Canada - National Science Library

    Takeuchi, N; Yamanashi, Y; Yoshikawa, N

    2014-01-01

    .... However, until now, no practical reversible logic gates have been demonstrated. One of the problems is that reversible logic gates must be built by using extremely energy-efficient logic devices...

  6. BEARING FORCES OF EMERGENCY GATE DURING SHUTOFF

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    For an emergency gate in a surge tank, forces acting on the gate were systematically tested and analyzed, including pulling forces resulted from water hammer because of the sudden rejection of all loads in turbine units under different gate levels, and forces during the process of gate shutoff under the conditions of different number of running turbine units. Besides, for the pulling force on the top of gate, their variation processes with time and extent of gate opening were also tested. It is shown that the calculated value of gate pulling force agrees on the whole with the tested one. The results indicate that the emergency gate in the extraordinary large surge tank of WWS hydropower station is safe under the above testing conditions. The related data in the present paper are helpful for the study on an emergency in a sure tank.

  7. Gating Technology for Vertically Parted Green Sand Moulds

    DEFF Research Database (Denmark)

    Larsen, Per

    Gating technology for vertically parted green sand moulds. Literature study of different ways of designing gating systems.......Gating technology for vertically parted green sand moulds. Literature study of different ways of designing gating systems....

  8. Kv channel gating requires a compatible S4-S5 linker and bottom part of S6, constrained by non-interacting residues.

    Science.gov (United States)

    Labro, Alain J; Raes, Adam L; Grottesi, Alessandro; Van Hoorick, Diane; Sansom, Mark S P; Snyders, Dirk J

    2008-12-01

    Voltage-dependent K(+) channels transfer the voltage sensor movement into gate opening or closure through an electromechanical coupling. To test functionally whether an interaction between the S4-S5 linker (L45) and the cytoplasmic end of S6 (S6(T)) constitutes this coupling, the L45 in hKv1.5 was replaced by corresponding hKv2.1 sequence. This exchange was not tolerated but could be rescued by also swapping S6(T). Exchanging both L45 and S6(T) transferred hKv2.1 kinetics to an hKv1.5 background while preserving the voltage dependence. A one-by-one residue substitution scan of L45 and S6(T) in hKv1.5 further shows that S6(T) needs to be alpha-helical and forms a "crevice" in which residues I422 and T426 of L45 reside. These residues transfer the mechanical energy onto the S6(T) crevice, whereas other residues in S6(T) and L45 that are not involved in the interaction maintain the correct structure of the coupling.

  9. Fabrication and characteristics of high-K HfO2 gate dielectrics on n-germanium

    Institute of Scientific and Technical Information of China (English)

    Han De-Dong; Kang Jin-Feng; Liu Xiao-Yan; Sun Lei; Luo Hao; Han Ru-Qi

    2007-01-01

    This paper reports that the high-K HfO2 gate dielectrics are fabricated on n-germanium substrates by sputtering Hf on Ge and following by a furnace annealing. The impacts of sputtering ambient, annealing ambient and annealing temperature on the electrical properties of high-K HfO2 gate dielectrics on germanium substrates are investigated.Experimental results indicate that high-K HfO2 gate dielectrics on germanium substrates with good electrical characteristics are obtained, the electrical properties of high-K HfO2 gate dielectrics is strongly correlated with sputtering ambient, annealing ambient and annealing temperature.

  10. Corticolimbic gating of emotion-driven punishment.

    Science.gov (United States)

    Treadway, Michael T; Buckholtz, Joshua W; Martin, Justin W; Jan, Katharine; Asplund, Christopher L; Ginther, Matthew R; Jones, Owen D; Marois, René

    2014-09-01

    Determining the appropriate punishment for a norm violation requires consideration of both the perpetrator's state of mind (for example, purposeful or blameless) and the strong emotions elicited by the harm caused by their actions. It has been hypothesized that such affective responses serve as a heuristic that determines appropriate punishment. However, an actor's mental state often trumps the effect of emotions, as unintended harms may go unpunished, regardless of their magnitude. Using fMRI, we found that emotionally graphic descriptions of harmful acts amplify punishment severity, boost amygdala activity and strengthen amygdala connectivity with lateral prefrontal regions involved in punishment decision-making. However, this was only observed when the actor's harm was intentional; when harm was unintended, a temporoparietal-medial-prefrontal circuit suppressed amygdala activity and the effect of graphic descriptions on punishment was abolished. These results reveal the brain mechanisms by which evaluation of a transgressor's mental state gates our emotional urges to punish.

  11. Interactions between S4-S5 linker and S6 transmembrane domain modulate gating of HERG K+ channels.

    Science.gov (United States)

    Tristani-Firouzi, Martin; Chen, Jun; Sanguinetti, Michael C

    2002-05-24

    Outward movement of the voltage sensor is coupled to activation in voltage-gated ion channels; however, the precise mechanism and structural basis of this gating event are poorly understood. Potential insight into the coupling mechanism was provided by our previous finding that mutation to Lys of a single residue (Asp(540)) located in the S4-S5 linker endowed HERG (human ether-a-go-go-related gene) K(+) channels with the unusual ability to open in response to membrane depolarization and hyperpolarization in a voltage-dependent manner. We hypothesized that the unusual hyperpolarization-induced gating occurred through an interaction between Lys(540) and the C-terminal end of the S6 domain, the region proposed to form the activation gate. Therefore, we mutated six residues located in this region of S6 (Ile(662)-Tyr(667)) to Ala in D540K HERG channels. Mutation of Arg(665), but not the other five residues, prevented hyperpolarization-dependent reopening of D540K HERG channels. Mutation of Arg(665) to Gln or Asp also prevented reopening. In addition, D540R and D540K/R665K HERG reopened in response to hyperpolarization. Together these findings suggest that a single residue (Arg(665)) in the S6 domain interacts with Lys(540) by electrostatic repulsion to couple voltage sensing to hyperpolarization-dependent opening of D540K HERG K(+) channels. Moreover, our findings suggest that the C-terminal ends of S4 and S6 are in close proximity at hyperpolarized membrane potentials.

  12. Gate-enclosed NMOS transistors

    Institute of Scientific and Technical Information of China (English)

    Fan Xue; Li Ping; Li Wei; Zhang Bin; Xie Xiaodong; Wang Gang; Hu Bin; Zhai Yahong

    2011-01-01

    In order to quantitatively compare the design cost and performance of various gate styles,NMOS transistors with two-edged,annular and ring gate layouts were designed and fabricated by a commercial 0.35 μm CMOS process.By comparing the minimum W/L ratios and transistor areas,it was found that either the annular layout or its ring counterpart incurs a higher area penalty that depends on the W/L ratio of the transistor to be designed.Furthermore,by comparing the output and transfer characteristics of the transistors and analyzing the popular existing methods for extracting the effective W/L ratio,it was shown that the mid-line approximation for annular NMOS could incur an error of more than 10%.It was also demonstrated that the foundry-provided extraction tool needs significant adaptation when being applied to the enclosed-gate transistors,since it is targeted only toward the two-edged transistor.A simple approach for rough extraction of the W/L ratio for the ring-gate NMOS was presented and its effectiveness was confirmed by the experimental results with an error up to 8%.

  13. Bill Gates eyes healthcare market.

    Science.gov (United States)

    Dunbar, C

    1995-02-01

    The entrepreneurial spirit is still top in Bill Gates' mind as he look toward healthcare and other growth industries. Microsoft's CEO has not intention of going the way of other large technology companies that became obsolete before they could compete today.

  14. Quantum Circuit Synthesis using a New Quantum Logic Gate Library of NCV Quantum Gates

    Science.gov (United States)

    Li, Zhiqiang; Chen, Sai; Song, Xiaoyu; Perkowski, Marek; Chen, Hanwu; Zhu, Wei

    2017-04-01

    Since Controlled-Square-Root-of-NOT (CV, CV‡) gates are not permutative quantum gates, many existing methods cannot effectively synthesize optimal 3-qubit circuits directly using the NOT, CNOT, Controlled-Square-Root-of-NOT quantum gate library (NCV), and the key of effective methods is the mapping of NCV gates to four-valued quantum gates. Firstly, we use NCV gates to create the new quantum logic gate library, which can be directly used to get the solutions with smaller quantum costs efficiently. Further, we present a novel generic method which quickly and directly constructs this new optimal quantum logic gate library using CNOT and Controlled-Square-Root-of-NOT gates. Finally, we present several encouraging experiments using these new permutative gates, and give a careful analysis of the method, which introduces a new idea to quantum circuit synthesis.

  15. Quantum Circuit Synthesis using a New Quantum Logic Gate Library of NCV Quantum Gates

    Science.gov (United States)

    Li, Zhiqiang; Chen, Sai; Song, Xiaoyu; Perkowski, Marek; Chen, Hanwu; Zhu, Wei

    2016-12-01

    Since Controlled-Square-Root-of-NOT (CV, CV‡) gates are not permutative quantum gates, many existing methods cannot effectively synthesize optimal 3-qubit circuits directly using the NOT, CNOT, Controlled-Square-Root-of-NOT quantum gate library (NCV), and the key of effective methods is the mapping of NCV gates to four-valued quantum gates. Firstly, we use NCV gates to create the new quantum logic gate library, which can be directly used to get the solutions with smaller quantum costs efficiently. Further, we present a novel generic method which quickly and directly constructs this new optimal quantum logic gate library using CNOT and Controlled-Square-Root-of-NOT gates. Finally, we present several encouraging experiments using these new permutative gates, and give a careful analysis of the method, which introduces a new idea to quantum circuit synthesis.

  16. Controlled phase gates based on two nonidentical quantum dots trapped in separate cavities

    Institute of Scientific and Technical Information of China (English)

    Wang Xiao-Xia; Zhang Jian-Qi; Yu Ya-Fei; Zhang Zhi-Ming

    2011-01-01

    We propose a scheme for realizing two-qubit controlled phase gates on two nonidentical quantum dots trapped in separate cavities.In our scheme,each dot simultaneously interacts with one highly detuned cavity mode and two strong driven classical fields.During the gate operation,the quantum dots undergo no transition,while the system can acquire different phases conditional on different states of the quantum dots.With the application of the single-qubit operations,two-qubit controlled phase gates can be realized.

  17. Total ionizing dose effects in multiple-gate field-effect transistor

    Science.gov (United States)

    Gaillardin, Marc; Marcandella, Claude; Martinez, Martial; Raine, Mélanie; Paillet, Philippe; Duhamel, Olivier; Richard, Nicolas

    2017-08-01

    This paper focuses on total ionizing dose (TID) effects induced in multiple-gate field-effect transistors. The impact of device architecture, geometry and scaling on the TID response of multiple-gate transistors is reviewed in both bulk and silicon-on-insulator (SOI) complementary metal-oxide-semiconductor (CMOS) technologies. These innovating devices exhibit specific ionizing dose responses which strongly depend on their three-dimensional nature. Their TID responses may look like the one usually observed in planar two-dimensional bulk or SOI transistors, but multiple-gate devices can also behave like any other CMOS device.

  18. Gate-induced blueshift and quenching of photoluminescence in suspended single-walled carbon nanotubes

    OpenAIRE

    Yasukochi, S.; Murai, T.; Moritsubo, S.; Shimada, T.; Chiashi, S.; Maruyama, S.; Kato, Y. K.

    2011-01-01

    Gate-voltage effects on photoluminescence spectra of suspended single-walled carbon nanotubes are investigated. Photoluminescence microscopy and excitation spectroscopy are used to identify individual nanotubes and to determine their chiralities. Under an application of gate voltage, we observe slight blueshifts in the emission energy and strong quenching of photoluminescence. The blueshifts are similar for different chiralities investigated, suggesting extrinsic mechanisms. In addition, we f...

  19. Differential effects of TipE and a TipE-homologous protein on modulation of gating properties of sodium channels from Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Lingxin Wang

    Full Text Available β subunits of mammalian sodium channels play important roles in modulating the expression and gating of mammalian sodium channels. However, there are no orthologs of β subunits in insects. Instead, an unrelated protein, TipE in Drosophila melanogaster and its orthologs in other insects, is thought to be a sodium channel auxiliary subunit. In addition, there are four TipE-homologous genes (TEH1-4 in D. melanogaster and three to four orthologs in other insect species. TipE and TEH1-3 have been shown to enhance the peak current of various insect sodium channels expressed in Xenopus oocytes. However, limited information is available on how these proteins modulate the gating of sodium channels, particularly sodium channel variants generated by alternative splicing and RNA editing. In this study, we compared the effects of TEH1 and TipE on the function of three Drosophila sodium channel splice variants, DmNav9-1, DmNav22, and DmNav26, in Xenopus oocytes. Both TipE and TEH1 enhanced the amplitude of sodium current and accelerated current decay of all three sodium channels tested. Strikingly, TEH1 caused hyperpolarizing shifts in the voltage-dependence of activation, fast inactivation and slow inactivation of all three variants. In contrast, TipE did not alter these gating properties except for a hyperpolarizing shift in the voltage-dependence of fast inactivation of DmNav26. Further analysis of the gating kinetics of DmNav9-1 revealed that TEH1 accelerated the entry of sodium channels into the fast inactivated state and slowed the recovery from both fast- and slow-inactivated states, thereby, enhancing both fast and slow inactivation. These results highlight the differential effects of TipE and TEH1 on the gating of insect sodium channels and suggest that TEH1 may play a broader role than TipE in regulating sodium channel function and neuronal excitability in vivo.

  20. Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25

    Directory of Open Access Journals (Sweden)

    Medler Kathryn F

    2006-03-01

    Full Text Available Abstract Background Taste receptor cells are responsible for transducing chemical stimuli from the environment and relaying information to the nervous system. Bitter, sweet and umami stimuli utilize G-protein coupled receptors which activate the phospholipase C (PLC signaling pathway in Type II taste cells. However, it is not known how these cells communicate with the nervous system. Previous studies have shown that the subset of taste cells that expresses the T2R bitter receptors lack voltage-gated Ca2+ channels, which are normally required for synaptic transmission at conventional synapses. Here we use two lines of transgenic mice expressing green fluorescent protein (GFP from two taste-specific promoters to examine Ca2+ signaling in subsets of Type II cells: T1R3-GFP mice were used to identify sweet- and umami-sensitive taste cells, while TRPM5-GFP mice were used to identify all cells that utilize the PLC signaling pathway for transduction. Voltage-gated Ca2+ currents were assessed with Ca2+ imaging and whole cell recording, while immunocytochemistry was used to detect expression of SNAP-25, a presynaptic SNARE protein that is associated with conventional synapses in taste cells. Results Depolarization with high K+ resulted in an increase in intracellular Ca2+ in a small subset of non-GFP labeled cells of both transgenic mouse lines. In contrast, no depolarization-evoked Ca2+ responses were observed in GFP-expressing taste cells of either genotype, but GFP-labeled cells responded to the PLC activator m-3M3FBS, suggesting that these cells were viable. Whole cell recording indicated that the GFP-labeled cells of both genotypes had small voltage-dependent Na+ and K+ currents, but no evidence of Ca2+ currents. A subset of non-GFP labeled taste cells exhibited large voltage-dependent Na+ and K+ currents and a high threshold voltage-gated Ca2+ current. Immunocytochemistry indicated that SNAP-25 was expressed in a separate population of taste cells

  1. Environmental noise reduction for holonomic quantum gates

    CERN Document Server

    Parodi, Daniele; Solinas, Paolo; Zanghì, Nino

    2007-01-01

    We study the performance of holonomic quantum gates, driven by lasers, under the effect of a dissipative environment modeled as a thermal bath of oscillators. We show how to enhance the performance of the gates by suitable choice of the loop in the manifold of the controllable parameters of the laser. For a simplified, albeit realistic model, we find the surprising result that for a long time evolution the performance of the gate (properly estimated in terms of average fidelity) increases. On the basis of this result, we compare holonomic gates with the so-called STIRAP gates.

  2. Modeling of the Channel Thickness Influence on Electrical Characteristics and Series Resistance in Gate-Recessed Nanoscale SOI MOSFETs

    Directory of Open Access Journals (Sweden)

    A. Karsenty

    2013-01-01

    Full Text Available Ultrathin body (UTB and nanoscale body (NSB SOI-MOSFET devices, sharing a similar W/L but with a channel thickness of 46 nm and lower than 5 nm, respectively, were fabricated using a selective “gate-recessed” process on the same silicon wafer. Their current-voltage characteristics measured at room temperature were found to be surprisingly different by several orders of magnitude. We analyzed this result by considering the severe mobility degradation and the influence of a huge series resistance and found that the last one seems more coherent. Then the electrical characteristics of the NSB can be analytically derived by integrating a gate voltage-dependent drain source series resistance. In this paper, the influence of the channel thickness on the series resistance is reported for the first time. This influence is integrated to the analytical model in order to describe the trends of the saturation current with the channel thickness. This modeling approach may be useful to interpret anomalous electrical behavior of other nanodevices in which series resistance and/or mobility degradation is of a great concern.

  3. In-depth study of the interaction, sensitivity and gating modulation by PUFAs on K+ channels; interaction and new targets

    Directory of Open Access Journals (Sweden)

    Cristina Moreno

    2016-11-01

    Full Text Available Voltage gated potassium channels (Kv are membrane proteins that allow selective flow of K+ ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs enhance or decrease the activity of several cardiac Kv channels. PUFAs-dependent modulation of potassium ion channels has been reported to be cardioprotective. However, the precise cellular mechanism underlying the cardiovascular benefits remained unclear in part because new PUFAs targets and signaling pathways continue being discovered. In this review, we will focus on recent data available concerning the following aspects of the Kv channel modulation by PUFAs: i the exact residues involved in PUFAs-Kv channels interaction; ii the structural PUFAs determinants important for their effects on Kv channels; iii the mechanism of the gating modulation of KV channels and, finally, iv the PUFAs modulation of a few new targets present in smooth muscle cells, KCa1.1, K2P and KATP channels, involved in vascular relaxation.

  4. In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on K+ Channels; Interaction and New Targets

    Science.gov (United States)

    Moreno, Cristina; de la Cruz, Alicia; Valenzuela, Carmen

    2016-01-01

    Voltage gated potassium channels (KV) are membrane proteins that allow selective flow of K+ ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes, and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs) enhance or decrease the activity of several cardiac KV channels. PUFAs-dependent modulation of potassium ion channels has been reported to be cardioprotective. However, the precise cellular mechanism underlying the cardiovascular benefits remained unclear in part because new PUFAs targets and signaling pathways continue being discovered. In this review, we will focus on recent data available concerning the following aspects of the KV channel modulation by PUFAs: (i) the exact residues involved in PUFAs-KV channels interaction; (ii) the structural PUFAs determinants important for their effects on KV channels; (iii) the mechanism of the gating modulation of KV channels and, finally, (iv) the PUFAs modulation of a few new targets present in smooth muscle cells (SMC), KCa1.1, K2P, and KATP channels, involved in vascular relaxation. PMID:27933000

  5. Strong vector valued integrals

    CERN Document Server

    Beckmann, Ralf

    2011-01-01

    Strong Bochner type integrals with values in locally convex spaces are introduced. It is shown that the strong integral exists in the same cases as the weak (Gelfand-Pettis) integral is known to exist. The strong integral has better continuity properties that the weak integral.

  6. Gate stack technology for nanoscale devices

    Directory of Open Access Journals (Sweden)

    Byoung Hun Lee

    2006-06-01

    Full Text Available Scaling of the gate stack has been a key to enhancing the performance of complementary metal-oxide-semiconductor (CMOS field-effect transistors (FETs of past technology generations. Because the rate of gate stack scaling has diminished in recent years, the motivation for alternative gate stacks or novel device structures has increased considerably. Intense research during the last decade has led to the development of high dielectric constant (k gate stacks that match the performance of conventional SiO2-based gate dielectrics. However, many challenges remain before alternative gate stacks can be introduced into mainstream technology. We review the current status of and challenges in gate stack research for planar CMOS devices and alternative device technologies to provide insights for future research.

  7. Digital-circuit analysis of short-gate tunnel FETs for low-voltage applications

    Science.gov (United States)

    Zhuge, Jing; Verhulst, Anne S.; Vandenberghe, William G.; Dehaene, Wim; Huang, Ru; Wang, Yangyuan; Groeseneken, Guido

    2011-08-01

    This paper investigates the potential of tunnel field-effect transistors (TFETs), with emphasis on short-gate TFETs, by simulation for low-power digital applications having a supply voltage lower than 0.5 V. A transient study shows that the tunneling current has a negligible contribution in charging and discharging the gate capacitance of TFETs. In spite of a higher resistance region in the short-gate TFET, the gate (dis)charging speed still meets low-voltage application requirements. A circuit analysis is performed on short-gate TFETs with different materials, such as Si, Ge and heterostructures in terms of voltage overshoot, delay, static power, energy consumption and energy delay product (EDP). These results are compared to MOSFET and full-gate TFET performance. It is concluded that short-gate heterostructure TFETs (Ge-source for nTFET, In0.6Ga0.4As-source for pTFET) are promising candidates to extend the supply voltage to lower than 0.5 V because they combine the advantage of a low Miller capacitance, due to the short-gate structures, and strong drive current in TFETs, due to the narrow bandgap material in the source. At a supply voltage of 0.4 V and for an EOT and channel length of 0.6 nm and 40 nm, respectively, a three-stage inverter chain based on short-gate heterostructure TFETs saves 40% energy consumption per cycle at the same delay and shows 60%-75% improvement of EDP at the same static power, compared to its full-gate counterpart. When compared to the MOSFET, better EDP can be achieved in the heterostructure TFET especially at low static power consumption.

  8. Uncoupling charge movement from channel opening in voltage-gated potassium channels by ruthenium complexes.

    Science.gov (United States)

    Jara-Oseguera, Andrés; Ishida, Itzel G; Rangel-Yescas, Gisela E; Espinosa-Jalapa, Noel; Pérez-Guzmán, José A; Elías-Viñas, David; Le Lagadec, Ronan; Rosenbaum, Tamara; Islas, León D

    2011-05-06

    The Kv2.1 channel generates a delayed-rectifier current in neurons and is responsible for modulation of neuronal spike frequency and membrane repolarization in pancreatic β-cells and cardiomyocytes. As with other tetrameric voltage-activated K(+)-channels, it has been proposed that each of the four Kv2.1 voltage-sensing domains activates independently upon depolarization, leading to a final concerted transition that causes channel opening. The mechanism by which voltage-sensor activation is coupled to the gating of the pore is still not understood. Here we show that the carbon-monoxide releasing molecule 2 (CORM-2) is an allosteric inhibitor of the Kv2.1 channel and that its inhibitory properties derive from the CORM-2 ability to largely reduce the voltage dependence of the opening transition, uncoupling voltage-sensor activation from the concerted opening transition. We additionally demonstrate that CORM-2 modulates Shaker K(+)-channels in a similar manner. Our data suggest that the mechanism of inhibition by CORM-2 may be common to voltage-activated channels and that this compound should be a useful tool for understanding the mechanisms of electromechanical coupling.

  9. Voltage-gated potassium currents within the dorsal vagal nucleus: inhibition by BDS toxin.

    Science.gov (United States)

    Dallas, Mark L; Morris, Neil P; Lewis, David I; Deuchars, Susan A; Deuchars, Jim

    2008-01-16

    Voltage-gated potassium (Kv) channels are essential components of neuronal excitability. The Kv3.4 channel protein is widely distributed throughout the central nervous system (CNS), where it can form heteromeric or homomeric Kv3 channels. Electrophysiological studies reported here highlight a functional role for this channel protein within neurons of the dorsal vagal nucleus (DVN). Current clamp experiments revealed that blood depressing substance (BDS) and intracellular dialysis of an anti-Kv3.4 antibody prolonged the action potential duration. In addition, a BDS sensitive, voltage-dependent, slowly inactivating outward current was observed in voltage clamp recordings from DVN neurons. Electrical stimulation of the solitary tract evoked EPSPs and IPSPs in DVN neurons and BDS increased the average amplitude and decreased the paired pulse ratio, consistent with a presynaptic site of action. This presynaptic modulation was action potential dependent as revealed by ongoing synaptic activity. Given the role of the Kv3 proteins in shaping neuronal excitability, these data highlight a role for homomeric Kv3.4 channels in spike timing and neurotransmitter release in low frequency firing neurons of the DVN.

  10. Markov chain Monte Carlo based analysis of post-translationally modified VDAC gating kinetics.

    Science.gov (United States)

    Tewari, Shivendra G; Zhou, Yifan; Otto, Bradley J; Dash, Ranjan K; Kwok, Wai-Meng; Beard, Daniel A

    2014-01-01

    The voltage-dependent anion channel (VDAC) is the main conduit for permeation of solutes (including nucleotides and metabolites) of up to 5 kDa across the mitochondrial outer membrane (MOM). Recent studies suggest that VDAC activity is regulated via post-translational modifications (PTMs). Yet the nature and effect of these modifications is not understood. Herein, single channel currents of wild-type, nitrosated, and phosphorylated VDAC are analyzed using a generalized continuous-time Markov chain Monte Carlo (MCMC) method. This developed method describes three distinct conducting states (open, half-open, and closed) of VDAC activity. Lipid bilayer experiments are also performed to record single VDAC activity under un-phosphorylated and phosphorylated conditions, and are analyzed using the developed stochastic search method. Experimental data show significant alteration in VDAC gating kinetics and conductance as a result of PTMs. The effect of PTMs on VDAC kinetics is captured in the parameters associated with the identified Markov model. Stationary distributions of the Markov model suggest that nitrosation of VDAC not only decreased its conductance but also significantly locked VDAC in a closed state. On the other hand, stationary distributions of the model associated with un-phosphorylated and phosphorylated VDAC suggest a reversal in channel conformation from relatively closed state to an open state. Model analyses of the nitrosated data suggest that faster reaction of nitric oxide with Cys-127 thiol group might be responsible for the biphasic effect of nitric oxide on basal VDAC conductance.

  11. Voltage-gated proton currents in microglia of distinct morphology and functional state.

    Science.gov (United States)

    Klee, R; Heinemann, U; Eder, C

    1999-01-01

    Whole-cell patch-clamp measurements were performed to investigate voltage-gated proton currents (I(PR)) in cultured murine microglia of distinct morphology and functional state. We studied I(PR) in ameboid microglia of untreated cultures, in ameboid microglia which had been activated by lipopolysaccharide, and in ramified microglia which had been exposed to astrocyte-conditioned medium. Proton currents of these three microglia populations did not differ regarding their activation threshold or the voltage dependence of steady-state activation. Moreover, pharmacological properties of I(PR) were similar: proton currents were sensitive to extracellularly applied Zn2+ or La3+, and could be abolished by each of those at a concentration of 100 microM. In the presence of extracellular Na+, I(PR) was decreased to a similar small extent due to activity of the Na+/H+ exchanger in all microglial populations. In contrast, proton currents of microglia differed between the three cell populations with respect to their current density and their time-course of activation: in comparison with untreated microglia, the current density of I(PR) was reduced by about 50% in microglia after their treatment with either lipopolysaccharide or astrocyte-conditioned medium. Moreover, I(PR) activated significantly more slowly in cells exposed to lipopolysaccharide or astrocyte-conditioned medium than in untreated cells. It can be concluded that the distinct H+ current characteristics of the three microglial populations do not correlate with the functional state of the cells.

  12. Regulation of Voltage-Activated K(+) Channel Gating by Transmembrane β Subunits.

    Science.gov (United States)

    Sun, Xiaohui; Zaydman, Mark A; Cui, Jianmin

    2012-01-01

    Voltage-activated K(+) (K(V)) channels are important for shaping action potentials and maintaining resting membrane potential in excitable cells. K(V) channels contain a central pore-gate domain (PGD) surrounded by four voltage-sensing domains (VSDs). The VSDs will change conformation in response to alterations of the membrane potential thereby inducing the opening of the PGD. Many K(V) channels are heteromeric protein complexes containing auxiliary β subunits. These β subunits modulate channel expression and activity to increase functional diversity and render tissue specific phenotypes. This review focuses on the K(V) β subunits that contain transmembrane (TM) segments including the KCNE family and the β subunits of large conductance, Ca(2+)- and voltage-activated K(+) (BK) channels. These TM β subunits affect the voltage-dependent activation of K(V) α subunits. Experimental and computational studies have described the structural location of these β subunits in the channel complexes and the biophysical effects on VSD activation, PGD opening, and VSD-PGD coupling. These results reveal some common characteristics and mechanistic insights into K(V) channel modulation by TM β subunits.

  13. Microscale Digital Vacuum Electronic Gates

    Science.gov (United States)

    Manohara, Harish (Inventor); Mojarradi, Mohammed M. (Inventor)

    2014-01-01

    Systems and methods in accordance with embodiments of the invention implement microscale digital vacuum electronic gates. In one embodiment, a microscale digital vacuum electronic gate includes: a microscale field emitter that can emit electrons and that is a microscale cathode; and a microscale anode; where the microscale field emitter and the microscale anode are disposed within at least a partial vacuum; where the microscale field emitter and the microscale anode are separated by a gap; and where the potential difference between the microscale field emitter and the microscale anode is controllable such that the flow of electrons between the microscale field emitter and the microscale anode is thereby controllable; where when the microscale anode receives a flow of electrons, a first logic state is defined; and where when the microscale anode does not receive a flow of electrons, a second logic state is defined.

  14. Concatenated hERG1 tetramers reveal stoichiometry of altered channel gating by RPR-260243.

    Science.gov (United States)

    Wu, Wei; Gardner, Alison; Sanguinetti, Michael C

    2015-01-01

    Activation of human ether-a-go-go-related gene 1 (hERG1) K(+) channels mediates repolarization of action potentials in cardiomyocytes. RPR-260243 [(3R,4R)-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluorophenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid] (RPR) slows deactivation and attenuates inactivation of hERG1 channels. A detailed understanding of the molecular mechanism of hERG1 agonists such as RPR may facilitate the design of more selective and potent compounds for prevention of arrhythmia associated with abnormally prolonged ventricular repolarization. RPR binds to a hydrophobic pocket located between two adjacent hERG1 subunits, and, hence, a homotetrameric channel has four identical RPR binding sites. To investigate the stoichiometry of altered channel gating induced by RPR, we constructed and characterized tetrameric hERG1 concatemers containing a variable number of wild-type subunits and subunits containing a point mutation (L553A) that rendered the channel insensitive to RPR, ostensibly by preventing ligand binding. The slowing of deactivation by RPR was proportional to the number of wild-type subunits incorporated into a concatenated tetrameric channel, and four wild-type subunits were required to achieve maximal slowing of deactivation. In contrast, a single wild-type subunit within a concatenated tetramer was sufficient to achieve half of the maximal RPR-induced shift in the voltage dependence of hERG1 inactivation, and maximal effect was achieved in channels containing three or four wild-type subunits. Together our findings suggest that the allosteric modulation of channel gating involves distinct mechanisms of coupling between drug binding and altered deactivation and inactivation.

  15. Niflumic acid alters gating of HCN2 pacemaker channels by interaction with the outer region of S4 voltage sensing domains.

    Science.gov (United States)

    Cheng, Lan; Sanguinetti, Michael C

    2009-05-01

    Niflumic acid, 2-[[3-(trifluoromethyl)phenyl]amino]pyridine-3-carboxylic acid (NFA), is a nonsteroidal anti-inflammatory drug that also blocks or modifies the gating of many ion channels. Here, we investigated the effects of NFA on hyperpolarization-activated cyclic nucleotide-gated cation (HCN) pacemaker channels expressed in X. laevis oocytes using site-directed mutagenesis and the two-electrode voltage-clamp technique. Extracellular NFA acted rapidly and caused a slowing of activation and deactivation and a hyperpolarizing shift in the voltage dependence of HCN2 channel activation (-24.5 +/- 1.2 mV at 1 mM). Slowed channel gating and reduction of current magnitude was marked in oocytes treated with NFA, while clamped at 0 mV but minimal in oocytes clamped at -100 mV, indicating the drug preferentially interacts with channels in the closed state. NFA at 0.1 to 3 mM shifted the half-point for channel activation in a concentration-dependent manner, with an EC(50) of 0.54 +/- 0.068 mM and a predicted maximum shift of -38 mV. NFA at 1 mM also reduced maximum HCN2 conductance by approximately 20%, presumably by direct block of the pore. The rapid onset and state-dependence of NFA-induced changes in channel gating suggests an interaction with the extracellular region of the S4 transmembrane helix, the primary voltage-sensing domain of HCN2. Neutralization (by mutation to Gln) of any three of the outer four basic charged residues in S4, but not single mutations, abrogated the NFA-induced shift in channel activation. We conclude that NFA alters HCN2 gating by interacting with the extracellular end of the S4 voltage sensor domains.

  16. Strongly Gorenstein Flat Dimensions

    Institute of Scientific and Technical Information of China (English)

    Chun Xia ZHANG; Li Min WANG

    2011-01-01

    This article is concerned with the strongly Gorenstein flat dimensions of modules and rings.We show this dimension has nice properties when the ring is coherent,and extend the well-known Hilbert's syzygy theorem to the strongly Gorenstein flat dimensions of rings.Also,we investigate the strongly Gorenstein flat dimensions of direct products of rings and (almost)excellent extensions of rings.

  17. Quantitative Determination on Ionic-Liquid-Gating Control of Interfacial Magnetism.

    Science.gov (United States)

    Zhao, Shishun; Zhou, Ziyao; Peng, Bin; Zhu, Mingmin; Feng, Mengmeng; Yang, Qu; Yan, Yuan; Ren, Wei; Ye, Zuo-Guang; Liu, Yaohua; Liu, Ming

    2017-03-03

    Ionic-liquid gating on a functional thin film with a low voltage has drawn a lot of attention due to rich chemical, electronic, and magnetic phenomena at the interface. Here, a key challenge in quantitative determination of voltage-controlled magnetic anisotropy (VCMA) in Au/[DEME](+) [TFSI](-) /Co field-effect transistor heterostructures is addressed. The magnetic anisotropy change as response to the gating voltage is precisely detected by in situ electron spin resonance measurements. A reversible change of magnetic anisotropy up to 219 Oe is achieved with a low gating voltage of 1.5 V at room temperature, corresponding to a record high VCMA coefficient of ≈146 Oe V(-1) . Two gating effects, the electrostatic doping and electrochemical reaction, are distinguished at various gating voltage regions, as confirmed by X-ray photoelectron spectroscopy and atomic force microscopy experiments. This work shows a unique ionic-liquid-gating system for strong interfacial magnetoelectric coupling with many practical advantages, paving the way toward ion-liquid-gating spintronic/electronic devices.

  18. STED nanoscopy with time-gated detection: theoretical and experimental aspects.

    Directory of Open Access Journals (Sweden)

    Giuseppe Vicidomini

    Full Text Available In a stimulated emission depletion (STED microscope the region in which fluorescence markers can emit spontaneously shrinks with continued STED beam action after a singular excitation event. This fact has been recently used to substantially improve the effective spatial resolution in STED nanoscopy using time-gated detection, pulsed excitation and continuous wave (CW STED beams. We present a theoretical framework and experimental data that characterize the time evolution of the effective point-spread-function of a STED microscope and illustrate the physical basis, the benefits, and the limitations of time-gated detection both for CW and pulsed STED lasers. While gating hardly improves the effective resolution in the all-pulsed modality, in the CW-STED modality gating strongly suppresses low spatial frequencies in the image. Gated CW-STED nanoscopy is in essence limited (only by the reduction of the signal that is associated with gating. Time-gated detection also reduces/suppresses the influence of local variations of the fluorescence lifetime on STED microscopy resolution.

  19. Final Technical GATE Report, 1998-2006

    Energy Technology Data Exchange (ETDEWEB)

    GATE Fuel Cell Vehicle Center

    2006-09-30

    In 1998, the U.S. Department of Energy (DOE) funded 10 proposals to establish graduate automotive technology education (GATE) centers of excellence at nine universities, each addressing a specific technological area. The University of California, Davis was chosen for two centers: Fuel Cell Center and Hybrid-Electric Vehicle Design Center (power drivetrains and control strategies). This report is specific to the Fuel Cell Center only, which was housed at the UC Davis Institute of Transportation Studies (ITS-Davis). ITS-Davis created the Fuel Cell Vehicle Center, with the following goals: (1) create an interdisciplinary fuel cell vehicle curriculum that cuts across engineering, the physical sciences and, to a lesser extent, the social sciences; (2) expand and strengthen the then-emerging multidisciplinary fuel cell vehicle research program; (3) strengthen links with industry; (4) create an active public outreach program; and (5) serve as neutral ground for interactions between academia, the auto, energy, and technology industries, government, and public-interest non-governmental organizations. At the time of proposal, the Center had a solid track record in fuel cell research, strong connections with industry, strong campus support, a core group of distinguished and motivated faculty, and an established institutional foundation for fuel cell vehicle research and education.

  20. Voltage gating by molecular subunits of Na+ and K+ ion channels: higher-dimensional cubic kinetics, rate constants, and temperature.

    Science.gov (United States)

    Fohlmeister, Jürgen F

    2015-06-01

    The structural similarity between the primary molecules of voltage-gated Na and K channels (alpha subunits) and activation gating in the Hodgkin-Huxley model is brought into full agreement by increasing the model's sodium kinetics to fourth order (m(3) → m(4)). Both structures then virtually imply activation gating by four independent subprocesses acting in parallel. The kinetics coalesce in four-dimensional (4D) cubic diagrams (16 states, 32 reversible transitions) that show the structure to be highly failure resistant against significant partial loss of gating function. Rate constants, as fitted in phase plot data of retinal ganglion cell excitation, reflect the molecular nature of the gating transitions. Additional dimensions (6D cubic diagrams) accommodate kinetically coupled sodium inactivation and gating processes associated with beta subunits. The gating transitions of coupled sodium inactivation appear to be thermodynamically irreversible; response to dielectric surface charges (capacitive displacement) provides a potential energy source for those transitions and yields highly energy-efficient excitation. A comparison of temperature responses of the squid giant axon (apparently Arrhenius) and mammalian channel gating yields kinetic Q10 = 2.2 for alpha unit gating, whose transitions are rate-limiting at mammalian temperatures; beta unit kinetic Q10 = 14 reproduces the observed non-Arrhenius deviation of mammalian gating at low temperatures; the Q10 of sodium inactivation gating matches the rate-limiting component of activation gating at all temperatures. The model kinetics reproduce the physiologically large frequency range for repetitive firing in ganglion cells and the physiologically observed strong temperature dependence of recovery from inactivation. Copyright © 2015 the American Physiological Society.

  1. NAND GATE USING FINFET FOR NANOSCALE TECHNOLOGY

    Directory of Open Access Journals (Sweden)

    Nirmal,

    2010-05-01

    Full Text Available In this paper we propose Double gate transistors (FinFETs are the substitutes for bulk CMOS evolving from a single gate devices into three dimensional devices with multiple gates (double gate, triple gate or quadruple-gate devices. The main drawback of using CMOS transistors are high power consumption and high leakage current. Enormous progress has been made to scale transistors to even smaller dimensions to obtain fast switching transistors, as well as to reduce the power consumption. Even though the device characteristics are improved, high active leakage remain a problem. Leakage is found to contribute more amount of total power consumption in power-optimized FinFET logic circuits. This paper mainly deals with the various logic design styles to obtain the Leakage power savings through the judicious use of FinFET logic styles.

  2. Reversible logic gate using adiabatic superconducting devices

    Science.gov (United States)

    Takeuchi, N.; Yamanashi, Y.; Yoshikawa, N.

    2014-09-01

    Reversible computing has been studied since Rolf Landauer advanced the argument that has come to be known as Landauer's principle. This principle states that there is no minimum energy dissipation for logic operations in reversible computing, because it is not accompanied by reductions in information entropy. However, until now, no practical reversible logic gates have been demonstrated. One of the problems is that reversible logic gates must be built by using extremely energy-efficient logic devices. Another difficulty is that reversible logic gates must be both logically and physically reversible. Here we propose the first practical reversible logic gate using adiabatic superconducting devices and experimentally demonstrate the logical and physical reversibility of the gate. Additionally, we estimate the energy dissipation of the gate, and discuss the minimum energy dissipation required for reversible logic operations. It is expected that the results of this study will enable reversible computing to move from the theoretical stage into practical usage.

  3. System and Method for Scan Range Gating

    Science.gov (United States)

    Zuk, David M. (Inventor); Lindemann, Scott (Inventor)

    2017-01-01

    A system for scanning light to define a range gated signal includes a pulsed coherent light source that directs light into the atmosphere, a light gathering instrument that receives the light modified by atmospheric backscatter and transfers the light onto an image plane, a scanner that scans collimated light from the image plane to form a range gated signal from the light modified by atmospheric backscatter, a control circuit that coordinates timing of a scan rate of the scanner and a pulse rate of the pulsed coherent light source so that the range gated signal is formed according to a desired range gate, an optical device onto which an image of the range gated signal is scanned, and an interferometer to which the image of the range gated signal is directed by the optical device. The interferometer is configured to modify the image according to a desired analysis.

  4. Cognitive mechanisms associated with auditory sensory gating.

    Science.gov (United States)

    Jones, L A; Hills, P J; Dick, K M; Jones, S P; Bright, P

    2016-02-01

    Sensory gating is a neurophysiological measure of inhibition that is characterised by a reduction in the P50 event-related potential to a repeated identical stimulus. The objective of this work was to determine the cognitive mechanisms that relate to the neurological phenomenon of auditory sensory gating. Sixty participants underwent a battery of 10 cognitive tasks, including qualitatively different measures of attentional inhibition, working memory, and fluid intelligence. Participants additionally completed a paired-stimulus paradigm as a measure of auditory sensory gating. A correlational analysis revealed that several tasks correlated significantly with sensory gating. However once fluid intelligence and working memory were accounted for, only a measure of latent inhibition and accuracy scores on the continuous performance task showed significant sensitivity to sensory gating. We conclude that sensory gating reflects the identification of goal-irrelevant information at the encoding (input) stage and the subsequent ability to selectively attend to goal-relevant information based on that previous identification.

  5. Carrier localization on surfaces of organic semiconductors gated with electrolytes.

    Science.gov (United States)

    Xia, Yu; Xie, Wei; Ruden, P Paul; Frisbie, C Daniel

    2010-07-16

    Organic semiconductor single crystals gated with electrolytes exhibit a pronounced maximum in channel conductance at hole densities >10(13)   cm(-2). The cause is a strong decrease in the hole mobility with increasing charge density, which is explained in terms of a percolation model that incorporates trapping of holes by ions at the semiconductor-electrolyte interface. In the case of rubrene crystals, the peak channel conductance occurs at hole densities near 3 × 10(13)  cm(-2). The magnitude of the effect will be large for semiconductors with low dielectric constants and narrow bandwidths, and thus is likely to be a general phenomenon in organic semiconductors gated with electrolytes.

  6. Optimal Control of High-Fidelity Quantum Gates in the Presence of Decoherence

    CERN Document Server

    Grace, M; Kosut, R; Lidar, D A; Rabitz, H; Walmsley, I; Brif, Constantin; Grace, Matthew; Kosut, Robert; Lidar, Daniel A.; Rabitz, Herschel; Walmsley, Ian

    2006-01-01

    This work studies the feasibility of optimal control of high-fidelity quantum gates in a model of interacting two-level particles. One set of particles serves as the quantum information processor, whose evolution is controlled by a time-dependent external field. The other particles are not directly controlled and serve as an effective environment, coupling to which is the source of decoherence. The control objective is to generate target one- and two-qubit gates in the presence of strong environmentally-induced decoherence and physically motivated restrictions on the control field. The quantum-gate fidelity, expressed in terms of a state-independent distance measure, is maximized with respect to the control field using combined genetic and gradient algorithms. The resulting high-fidelity gates demonstrate the utility of optimal control for precise management of quantum dynamics, especially when the system complexity is exacerbated by environmental coupling.

  7. Implementation of an experimentally feasible controlled-phase gate on two blockaded Rydberg atoms

    Science.gov (United States)

    Müller, Matthias M.; Murphy, Michael; Montangero, Simone; Calarco, Tommaso; Grangier, Philippe; Browaeys, Antoine

    2014-03-01

    We investigate the implementation of a controlled-Z gate on a pair of Rydberg atoms in spatially separated dipole traps where the joint excitation of both atoms into the Rydberg level is strongly suppressed (the Rydberg blockade). We follow the adiabatic gate scheme of Jaksch et al. [D. Jaksch, J. I. Cirac, P. Zoller, S. L. Rolston, R. Côté, and M. D. Lukin, Phys. Rev. Lett. 85, 2208 (2000), 10.1103/PhysRevLett.85.2208], where the pair of atoms is coherently excited using lasers, and apply it to the experimental setup outlined by Gaëtan et al. [A. Gaëtan, Y. Miroshnychenko, T. Wilk, A. Chotia, M. Viteau, D. Comparat, P. Pillet, A. Browaeys, and P. Grangier, Nat. Phys. 5, 115 (2009), 10.1038/nphys1183]. We apply optimization to the experimental parameters to improve gate fidelity and consider the impact of several experimental constraints on the gate success.

  8. Searching for economic rationale behind gated communities: a public choice approach.

    Science.gov (United States)

    Cséfalvay, Zoltán

    2011-01-01

    As millions of people world-wide now live in residential areas with restricted access to the public, the ascent of gated communities can no longer be attributed to incidental or deviant development. Hence this paper makes an attempt to discover the economic rationale behind the gated community phenomenon; it discusses the mainstream theses and outlines 10 theorems for an alternative proposition based on theories of public choice and fiscal federalism. The core theorem asserts that a centrally featured system of government diminishes the ability of local municipalities properly to reflect citizens' demands for local public goods and services, and that this constitutes a strong incentive for people to move into gated communities. In particular, gated and guarded residential developments represent an exit option when local municipalities fail to deploy vital governmental rules and instruments, such as fiscal equivalence and benefit taxation.

  9. Non-Perturbative Entangling Gates between Distant Qubits using Uniform Cold Atom Chains

    CERN Document Server

    Banchi, Leonardo; Verrucchi, Paola; Bose, Sougato

    2010-01-01

    We propose a new fast scalable method for achieving a two-qubit entangling quantum gate between arbitrary distant qubits in a network by exploiting dispersionless propagation in uniform chains. This is achieved dynamically by switching on a strong interaction between the qubits and a bus formed by a non-engineered chain of interacting qubits. The quality of the gate scales very efficiently with qubit separations. Surprisingly, a sudden switching of the coupling is not necessary and our gate mechanism is not altered by a possibly gradual switching. The bus is also naturally reset to its initial state making the complex resetting procedure unnecessary after each application of the gate. Moreover, we propose a possible experimental realization in cold atoms trapped in optical lattices and near field Fresnel trapping potentials, which are both accessible to current technology.

  10. Designing quantum gates using the genetic algorithm

    Science.gov (United States)

    Kumar, Karthikeyan S.; Paraoanu, G. S.

    2012-12-01

    We demonstrate the usage of Genetic Algorithm (GA) to tailor the radio frequency pulses for producing unitary transformations in qubit systems. We find that the initial population converges to the optimal solution after 10 generations, for a one segment pulse corresponding to single qubit Hadamard gate. For a two qubit CNOT gate, we see the population convergence for a two segment pulse after 150 generations. This demonstrates that the method is suitable for designing quantum gates.

  11. Floating gate transistors as biosensors (Conference Presentation)

    Science.gov (United States)

    Frisbie, C. Daniel

    2016-11-01

    Electrolyte gated transistors (EGTs) are a sub-class of thin film transistors that are extremely promising for biological sensing applications. These devices employ a solid electrolyte as the gate insulator; the very large capacitance of the electrolyte results in low voltage operation and high transconductance or gain. This talk will describe the fabrication of floating gate EGTs and their use as ricin sensors. The critical performance metrics for EGTs compared with other types of TFTs will also be reviewed.

  12. Bubbles, Gating, and Anesthetics in Ion Channels

    OpenAIRE

    Roth, Roland, imp.; Gillespie, Dirk; Nonner, Wolfgang; Eisenberg, Robert E.

    2008-01-01

    We suggest that bubbles are the bistable hydrophobic gates responsible for the on-off transitions of single channel currents. In this view, many types of channels gate by the same physical mechanism—dewetting by capillary evaporation—but different types of channels use different sensors to modulate hydrophobic properties of the channel wall and thereby trigger and control bubbles and gating. Spontaneous emptying of channels has been seen in many simulations. Because of the physics involved, s...

  13. Criteria for universality of quantum gates

    Science.gov (United States)

    Sawicki, Adam; Karnas, Katarzyna

    2017-06-01

    We consider the problem of deciding if a set of quantum one-qudit gates S ={U1,...,Un} is universal. We provide the compact-form criteria leading to a simple algorithm that allows deciding the universality of any given set of gates in a finite number of steps. Moreover, for a nonuniversal S our criteria indicate what types of gates can be added to S to turn it into a universal set.

  14. Interactions between permeation and gating in the TMEM16B/anoctamin2 calcium-activated chloride channel.

    Science.gov (United States)

    Betto, Giulia; Cherian, O Lijo; Pifferi, Simone; Cenedese, Valentina; Boccaccio, Anna; Menini, Anna

    2014-06-01

    At least two members of the TMEM16/anoctamin family, TMEM16A (also known as anoctamin1) and TMEM16B (also known as anoctamin2), encode Ca(2+)-activated Cl(-) channels (CaCCs), which are found in various cell types and mediate numerous physiological functions. Here, we used whole-cell and excised inside-out patch-clamp to investigate the relationship between anion permeation and gating, two processes typically viewed as independent, in TMEM16B expressed in HEK 293T cells. The permeability ratio sequence determined by substituting Cl(-) with other anions (PX/PCl) was SCN(-) > I(-) > NO3 (-) > Br(-) > Cl(-) > F(-) > gluconate. When external Cl(-) was substituted with other anions, TMEM16B activation and deactivation kinetics at 0.5 µM Ca(2+) were modified according to the sequence of permeability ratios, with anions more permeant than Cl(-) slowing both activation and deactivation and anions less permeant than Cl(-) accelerating them. Moreover, replacement of external Cl(-) with gluconate, or sucrose, shifted the voltage dependence of steady-state activation (G-V relation) to more positive potentials, whereas substitution of extracellular or intracellular Cl(-) with SCN(-) shifted G-V to more negative potentials. Dose-response relationships for Ca(2+) in the presence of different extracellular anions indicated that the apparent affinity for Ca(2+) at +100 mV increased with increasing permeability ratio. The apparent affinity for Ca(2+) in the presence of intracellular SCN(-) also increased compared with that in Cl(-). Our results provide the first evidence that TMEM16B gating is modulated by permeant anions and provide the basis for future studies aimed at identifying the molecular determinants of TMEM16B ion selectivity and gating.

  15. Circuits with arbitrary gates for random operators

    CERN Document Server

    Jukna, S

    2010-01-01

    We consider boolean circuits computing n-operators f:{0,1}^n --> {0,1}^n. As gates we allow arbitrary boolean functions; neither fanin nor fanout of gates is restricted. An operator is linear if it computes n linear forms, that is, computes a matrix-vector product y=Ax over GF(2). We prove the existence of n-operators requiring about n^2 wires in any circuit, and linear n-operators requiring about n^2/\\log n wires in depth-2 circuits, if either all output gates or all gates on the middle layer are linear.

  16. Non-gated laser-induced breakdown spectroscopy in bulk water by position-selective detection

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Ye; Xue, Boyang; Song, Jiaojian; Lu, Yuan; Zheng, Ronger, E-mail: rzheng@ouc.edu.cn [Optics and Optoelectronics Laboratory, Ocean University of China, Qingdao 266100 (China)

    2015-09-14

    Temporal and spatial evolutions of the laser-induced plasma in bulk water are investigated using fast imaging and emission spectroscopic techniques. By tightly focusing a single-pulse nanosecond Nd: YAG laser beam into the bulk water, we generate a strongly expanded plasma with high reproducibility. Such a strong expanding plasma enables us to obtain well-resolved spectral lines by means of position-selective detection; hence, the time-gated detector becomes abdicable. The present results suggest not only a possible non-gated approach for underwater laser-induced breakdown spectroscopy but also give an insight into the plasma generation and expansion in bulk water.

  17. Overview Of Pulsers For Nanosecond Gating Of Image Shutter Tubes

    Science.gov (United States)

    Yates, G. J.; Ogle, J. W.; King, N. S.; Aeby, I.

    1983-03-01

    The capability of generating a useful optical shutter of a few nanoseconds or less utilizing gated proximity-focussed microchannel-plate (MCP) wafer tubes or silicon intensified target (SIT) vidicon tubes depends strongly on the driving electrical pulse. A proximity-focussed MCP wafer tube can be optically shuttered by applying a short electrical pulse between the photocathode and MCP interface.' This interface is electrically reverse-biased by approximately 30V to prevent photocathode electrons from reaching the MCP. The gating pulse, typically 80V, is of opposite polarity to generate an effective forward bias to "shutter" the system. Light intensity ratios for gated on to off conditions (shutter ratios) of greater than 105 are obtained. The more recently developed gated SIT vidicon tubes2 are gated by applying an effective forward bias between the photocathode and a 50% transmission grid in close proximity to the photocathode. Equivalent shutter ratios have not been achieved as yet, with 103 shuttering efficiency measured for typical SITs. Assuming the optical gate width is determined by the electrical gate width one requires pulses with rise and fall times of less than a nanosecond and amplitudes in excess of 80 volts into a 50 ohm impedance. Such pulses have permitted shutter times of %1.5 ns and L800 ps for the MCP and SIT tube systems respectively while preserving their resolution capabilities. The problem of matching an electrical pulser's driving impedance to that of the optical shutter is one still under study. The intrinsit impedance of a proximity-focussed MCP optical shutter is that of a distributed capacitance and resistance.1r3 A measurement of the resistance and capacitance vs a frequency network of 10 MHz with an HP4191A impedance analyser indicated a relatively constant equivalent series capacitance of 31 pf and a photocathode equivalent series resistance in the range from 120 MHz, and therefore gate rise times less than %3 ns, the equivalent

  18. Strong Field, Noncommutative QED

    Directory of Open Access Journals (Sweden)

    Anton Ilderton

    2010-05-01

    Full Text Available We review the effects of strong background fields in noncommutative QED. Beginning with the noncommutative Maxwell and Dirac equations, we describe how combined noncommutative and strong field effects modify the propagation of fermions and photons. We extend these studies beyond the case of constant backgrounds by giving a new and revealing interpretation of the photon dispersion relation. Considering scattering in background fields, we then show that the noncommutative photon is primarily responsible for generating deviations from strong field QED results. Finally, we propose a new method for constructing gauge invariant variables in noncommutative QED, and use it to analyse the physics of our null background fields.

  19. Gated Graphene Electrical Transport Characterization

    Directory of Open Access Journals (Sweden)

    Josef Náhlík

    2012-01-01

    Full Text Available Graphene is a very interesting new material, and promises attractive applications in future nanodevices. It is a 2D carbon structure with very interesting physical behavior. Graphene is an almost transparent material that has higher carrier mobility than any other material at room temperature. Graphene can therefore be used in applications such as ultrahigh-speed transistors and transparent electrodes. In this paper, we present our preliminary experiments on the transport behavior of graphene at room temperature. We measured the resistivity of Hall-bar samples depending on gate voltage (backgated graphene. Hysteresis between the forward and backward sweep direction was observed.

  20. How strong is the strong interaction?

    Energy Technology Data Exchange (ETDEWEB)

    Blomgren, J.; Bergenwall, B.; Hildebrand, A.; Johansson, C.; Klug, J.; Mermod, P.; Nilsson, L.; Pomp, S.; Oesterlund, M. [Dept. of Neutron Research, Uppsala Univ., Uppsala (Sweden); Tippawan, U. [Dept. of Neutron Research, Uppsala Univ., Uppsala (Sweden)]|[Fast Neutron Research Facility, Dept. of Physics, Chiang Mai Univ. (Thailand); Jonsson, O.; Prokofiev, A.V. [The Svedberg Lab., Uppsala Univ., Uppsala (Sweden); Nadel-Turonski, P. [Dept. of Radiation Sciences, Uppsala Univ., Uppsala (Sweden); Olsson, N. [Dept. of Neutron Research, Uppsala Univ., Uppsala (Sweden)]|[Swedish Defence Research Agency, Stockholm (Sweden); Dangtip, S. [Fast Neutron Research Facility, Dept. of Physics, Chiang Mai Univ. (Thailand)

    2003-07-01

    Elastic neutron scattering plays a key role in establishing the neutron-nucleus potential, i.e., the interaction strength between a neutron and a nucleus. In ADS applications, this information is useful in many different ways. Elastic scattering data are needed when determining the neutron intensity profile in and ADS system. In addition, the optical potentials derived from elastic neutron scattering data are used as input in every model calculation with a neutron in the incident or exit channel. Recently, there has been intense international debate on the neutron-proton scattering cross section. In the global data base, the backward cross section differs by 10% or even more at energies above 100 MeV. It is difficult to overemphasize the importance of this issue. The np scattering cross section is used as cross section reference in essentially all measurements of neutron-induced cross sections. Thus, for many applied cross sections the absolute scale is uncertain by the same amount. Moreover, the np scattering cross section has been used to derive the pion-nucleon coupling constant, i.e., the absolute strength of the strong interaction. It is annoying to have such a large uncertainty for such a fundamental parameter. We are presenting new data on elastic neutron scattering at 96 MeV from {sup 12}C and {sup 208}Pb, where the latter is part of the HINDAS project. In addition, new data on np scattering at 190 MeV will be presented. The impact on ADS and fundamental physics will be discussed. (orig.)

  1. Strong Cosmic Censorship

    Science.gov (United States)

    Isenberg, James

    2017-01-01

    The Hawking-Penrose theorems tell us that solutions of Einstein's equations are generally singular, in the sense of the incompleteness of causal geodesics (the paths of physical observers). These singularities might be marked by the blowup of curvature and therefore crushing tidal forces, or by the breakdown of physical determinism. Penrose has conjectured (in his `Strong Cosmic Censorship Conjecture`) that it is generically unbounded curvature that causes singularities, rather than causal breakdown. The verification that ``AVTD behavior'' (marked by the domination of time derivatives over space derivatives) is generically present in a family of solutions has proven to be a useful tool for studying model versions of Strong Cosmic Censorship in that family. I discuss some of the history of Strong Cosmic Censorship, and then discuss what is known about AVTD behavior and Strong Cosmic Censorship in families of solutions defined by varying degrees of isometry, and discuss recent results which we believe will extend this knowledge and provide new support for Strong Cosmic Censorship. I also comment on some of the recent work on ``Weak Null Singularities'', and how this relates to Strong Cosmic Censorship.

  2. Stimuli-responsive smart gating membranes.

    Science.gov (United States)

    Liu, Zhuang; Wang, Wei; Xie, Rui; Ju, Xiao-Jie; Chu, Liang-Yin

    2016-02-07

    Membranes are playing paramount roles in the sustainable development of myriad fields such as energy, environmental and resource management, and human health. However, the unalterable pore size and surface properties of traditional porous membranes restrict their efficient applications. The performances of traditional membranes will be weakened upon unavoidable membrane fouling, and they cannot be applied to cases where self-regulated permeability and selectivity are required. Inspired by natural cell membranes with stimuli-responsive channels, artificial stimuli-responsive smart gating membranes are developed by chemically/physically incorporating stimuli-responsive materials as functional gates into traditional porous membranes, to provide advanced functions and enhanced performances for breaking the bottlenecks of traditional membrane technologies. Smart gating membranes, integrating the advantages of traditional porous membrane substrates and smart functional gates, can self-regulate their permeability and selectivity via the flexible adjustment of pore sizes and surface properties based on the "open/close" switch of the smart gates in response to environmental stimuli. This tutorial review summarizes the recent developments in stimuli-responsive smart gating membranes, including the design strategies and the fabrication strategies that are based on the introduction of the stimuli-responsive gates after or during membrane formation, and the positively and negatively responsive gating models of versatile stimuli-responsive smart gating membranes, as well as the advanced applications of smart gating membranes for regulating substance concentration in reactors, controlling the release rate of drugs, separating active molecules based on size or affinity, and the self-cleaning of membrane surfaces. With self-regulated membrane performances, smart gating membranes show great power for use in global sustainable development.

  3. Multisensor Distributed Track Fusion AlgorithmBased on Strong Tracking Filter and Feedback Integration1)

    Institute of Scientific and Technical Information of China (English)

    YANGGuo-Sheng; WENCheng-Lin; TANMin

    2004-01-01

    A new multisensor distributed track fusion algorithm is put forward based on combiningthe feedback integration with the strong tracking Kalman filter. Firstly, an effective tracking gateis constructed by taking the intersection of the tracking gates formed before and after feedback.Secondly, on the basis of the constructed effective tracking gate, probabilistic data association andstrong tracking Kalman filter are combined to form the new multisensor distributed track fusionalgorithm. At last, simulation is performed on the original algorithm and the algorithm presented.

  4. Nanosecond gating properties of proximity focused microchannel plate image intensifiers

    Science.gov (United States)

    King, N. S. P.; King, N. S. P.; Yates, G. J.; Jaramillo, S. A.; Noel, B. W.; Detch, J. L., Jr.; Ogle, J. W.

    The optical gating properties of Multichannel plate image intensifiers were characterized. Emphasis was placed on parameters relevant to gating speed and correlations between the applied electrical and resultant optical gates.

  5. Transparently wrap-gated semiconductor nanowire arrays for studies of gate-controlled photoluminescence

    Energy Technology Data Exchange (ETDEWEB)

    Nylund, Gustav; Storm, Kristian; Torstensson, Henrik; Wallentin, Jesper; Borgström, Magnus T.; Hessman, Dan; Samuelson, Lars [Solid State Physics, Nanometer Structure Consortium, Lund University, Box 118, S-221 00 Lund (Sweden)

    2013-12-04

    We present a technique to measure gate-controlled photoluminescence (PL) on arrays of semiconductor nanowire (NW) capacitors using a transparent film of Indium-Tin-Oxide (ITO) wrapping around the nanowires as the gate electrode. By tuning the wrap-gate voltage, it is possible to increase the PL peak intensity of an array of undoped InP NWs by more than an order of magnitude. The fine structure of the PL spectrum reveals three subpeaks whose relative peak intensities change with gate voltage. We interpret this as gate-controlled state-filling of luminescing quantum dot segments formed by zincblende stacking faults in the mainly wurtzite NW crystal structure.

  6. Effects of different kinds of stretch on voltage-dependent calcium current in antrial circular smooth muscle cells of the guinea-pig%不同牵张刺激对豚鼠胃窦环行肌细胞电压依赖性钙电流的影响

    Institute of Scientific and Technical Information of China (English)

    许文燮; 李英; 吴龙仁; 李在琉

    2000-01-01

    利用全细胞膜片钳技术,在胃窦环行肌细胞上观察了不同方式的牵张刺激对电压依赖性钙电流的影响,探讨牵张刺激对胃窦平滑肌细胞电压依赖性钙电流的作用.用低渗性溶液灌流细胞引起的牵张刺激首先增加电压依赖性钙电流,接着激活一种内向性钳制电流.钙电流的增加发生在灌流后1 min内,而内向性钳制电流在细胞明显膨胀之后缓慢激活.低渗和正压引起的细胞膨胀明显增加电压依赖性钙离子电流,而利用两个电极直接牵拉细胞则不出现钙电流增加效应.结果提示: 细胞膜牵张增强电压依赖性钙通道的活性,而这一作用可能与牵拉引起的细胞所受的膜张力或/和牵拉的方向有关.%In order to elucidate the effect of membrane stretch on ionic currents, we employed the whole-cell patch-clamp technique to investigate the effects of different kinds of stretch on voltage-dependent calcium currents in antrial circular smooth muscle cells of the guinea-pig. The membrane stretch induced by superfusing the smooth muscle cells with hyposmotic bath solution enhanced voltage-operated calcium current and activated inward holding current. The increase in calcium current occurred within 1 minute of superfusion and the sustained inward holding current was slowly activated after prominent cell swelling. Voltage-dependent calcium currents (Ica) were significantly increased by membrane stretch which was induced by cell swelling and cell inflation, but was not affected by direct longitudinal stretch (110~130%) using two electrodes.The results suggest that the cell membrane stretch can increase voltage-dependent calcium channel activity and the effect of stretch on calcium channels was related to the membrane tension and/or the direction of membrane stretch.

  7. Protected gates for topological quantum field theories

    Energy Technology Data Exchange (ETDEWEB)

    Beverland, Michael E.; Pastawski, Fernando; Preskill, John [Institute for Quantum Information and Matter, California Institute of Technology, Pasadena, California 91125 (United States); Buerschaper, Oliver [Dahlem Center for Complex Quantum Systems, Freie Universität Berlin, 14195 Berlin (Germany); Koenig, Robert [Institute for Advanced Study and Zentrum Mathematik, Technische Universität München, 85748 Garching (Germany); Sijher, Sumit [Institute for Quantum Computing and Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada)

    2016-02-15

    We study restrictions on locality-preserving unitary logical gates for topological quantum codes in two spatial dimensions. A locality-preserving operation is one which maps local operators to local operators — for example, a constant-depth quantum circuit of geometrically local gates, or evolution for a constant time governed by a geometrically local bounded-strength Hamiltonian. Locality-preserving logical gates of topological codes are intrinsically fault tolerant because spatially localized errors remain localized, and hence sufficiently dilute errors remain correctable. By invoking general properties of two-dimensional topological field theories, we find that the locality-preserving logical gates are severely limited for codes which admit non-abelian anyons, in particular, there are no locality-preserving logical gates on the torus or the sphere with M punctures if the braiding of anyons is computationally universal. Furthermore, for Ising anyons on the M-punctured sphere, locality-preserving gates must be elements of the logical Pauli group. We derive these results by relating logical gates of a topological code to automorphisms of the Verlinde algebra of the corresponding anyon model, and by requiring the logical gates to be compatible with basis changes in the logical Hilbert space arising from local F-moves and the mapping class group.

  8. TRADITIONAL WOODEN GATES IN THE SZEKLER LAND

    Directory of Open Access Journals (Sweden)

    GhiorghiŃă Nicolaie COMSA

    2013-09-01

    Full Text Available This paper presents specific aspects oftraditional wooden gates built in the rural area of thecounty of Harghita in Romania. One can see the loveand appreciation given to woodworking and outdoorelements of household adornment, beautiful insidetransmitted outside. Constructive elements andornaments are given specific geographical area.These gates belong to our national cultural heritage.

  9. Dual-Gate p-GaN Gate High Electron Mobility Transistors for Steep Subthreshold Slope.

    Science.gov (United States)

    Bae, Jong-Ho; Lee, Jong-Ho

    2016-05-01

    A steep subthreshold slope characteristic is achieved through p-GaN gate HEMT with dual-gate structure. Obtained subthreshold slope is less than 120 μV/dec. Based on the measured and simulated data obtained from single-gate device, breakdown of parasitic floating-base bipolar transistor and floating gate charged with holes are responsible to increase abruptly in drain current. In the dual-gate device, on-current degrades with high temperature but subthreshold slope is not changed. To observe the switching speed of dual-gate device and transient response of drain current are measured. According to the transient responses of drain current, switching speed of the dual-gate device is about 10(-5) sec.

  10. Logic gates based on ion transistors.

    Science.gov (United States)

    Tybrandt, Klas; Forchheimer, Robert; Berggren, Magnus

    2012-05-29

    Precise control over processing, transport and delivery of ionic and molecular signals is of great importance in numerous fields of life sciences. Integrated circuits based on ion transistors would be one approach to route and dispense complex chemical signal patterns to achieve such control. To date several types of ion transistors have been reported; however, only individual devices have so far been presented and most of them are not functional at physiological salt concentrations. Here we report integrated chemical logic gates based on ion bipolar junction transistors. Inverters and NAND gates of both npn type and complementary type are demonstrated. We find that complementary ion gates have higher gain and lower power consumption, as compared with the single transistor-type gates, which imitates the advantages of complementary logics found in conventional electronics. Ion inverters and NAND gates lay the groundwork for further development of solid-state chemical delivery circuits.

  11. Airport Gate Assignment: New Model and Implementation

    CERN Document Server

    Li, Chendong

    2008-01-01

    Airport gate assignment is of great importance in airport operations. In this paper, we study the Airport Gate Assignment Problem (AGAP), propose a new model and implement the model with Optimization Programming language (OPL). With the objective to minimize the number of conflicts of any two adjacent aircrafts assigned to the same gate, we build a mathematical model with logical constraints and the binary constraints, which can provide an efficient evaluation criterion for the Airlines to estimate the current gate assignment. To illustrate the feasibility of the model we construct experiments with the data obtained from Continental Airlines, Houston Gorge Bush Intercontinental Airport IAH, which indicate that our model is both energetic and effective. Moreover, we interpret experimental results, which further demonstrate that our proposed model can provide a powerful tool for airline companies to estimate the efficiency of their current work of gate assignment.

  12. Gating of Permanent Molds for ALuminum Casting

    Energy Technology Data Exchange (ETDEWEB)

    David Schwam; John F. Wallace; Tom Engle; Qingming Chang

    2004-03-30

    This report summarizes a two-year project, DE-FC07-01ID13983 that concerns the gating of aluminum castings in permanent molds. The main goal of the project is to improve the quality of aluminum castings produced in permanent molds. The approach taken was determine how the vertical type gating systems used for permanent mold castings can be designed to fill the mold cavity with a minimum of damage to the quality of the resulting casting. It is evident that somewhat different systems are preferred for different shapes and sizes of aluminum castings. The main problems caused by improper gating are entrained aluminum oxide films and entrapped gas. The project highlights the characteristic features of gating systems used in permanent mold aluminum foundries and recommends gating procedures designed to avoid common defects. The study also provides direct evidence on the filling pattern and heat flow behavior in permanent mold castings.

  13. Glare suppression by coherence gated negation

    CERN Document Server

    Zhou, Edward Haojiang; Brake, Joshua; Ruan, Haowen; Yang, Changhuei

    2016-01-01

    Imaging of a weak target hidden behind a scattering medium can be significantly confounded by glare. We report a method, termed coherence gated negation (CGN), that uses destructive optical interference to suppress glare and allow improved imaging of a weak target. As a demonstration, we show that by permuting through a set range of amplitude and phase values for a reference beam interfering with the optical field from the glare and target reflection, we can suppress glare by an order of magnitude, even when the optical wavefront is highly disordered. This strategy significantly departs from conventional coherence gating methods in that CGN actively 'gates out' the unwanted optical contributions while conventional methods 'gate in' the target optical signal. We further show that the CGN method can outperform conventional coherence gating image quality in certain scenarios by more effectively rejecting unwanted optical contributions.

  14. Strongly correlated Bose gases

    Science.gov (United States)

    Chevy, F.; Salomon, C.

    2016-10-01

    The strongly interacting Bose gas is one of the most fundamental paradigms of quantum many-body physics and the subject of many experimental and theoretical investigations. We review recent progress on strongly correlated Bose gases, starting with a description of beyond mean-field corrections. We show that the Efimov effect leads to non universal phenomena and to a metastability of the low temperature Bose gas through three-body recombination to deeply bound molecular states. We outline differences and similarities with ultracold Fermi gases, discuss recent experiments on the unitary Bose gas, and finally present a few perspectives for future research.

  15. Abortion: Strong's counterexamples fail

    DEFF Research Database (Denmark)

    Di Nucci, Ezio

    2009-01-01

    This paper shows that the counterexamples proposed by Strong in 2008 in the Journal of Medical Ethics to Marquis's argument against abortion fail. Strong's basic idea is that there are cases--for example, terminally ill patients--where killing an adult human being is prima facie seriously morally......'s scenarios have some valuable future or admitted that killing them is not seriously morally wrong. Finally, if "valuable future" is interpreted as referring to objective standards, one ends up with implausible and unpalatable moral claims....

  16. Description of interacting channel gating using a stochastic Markovian model.

    Science.gov (United States)

    Manivannan, K; Mathias, R T; Gudowska-Nowak, E

    1996-01-01

    Single-channel recordings from membrane patches frequently exhibit multiple conductance levels. In some preparations, the steady-state probabilities of observing these levels do not follow a binomial distribution. This behavior has been reported in sodium channels, potassium channels, acetylcholine receptor channels and gap junction channels. A non-binomial distribution suggests interaction of the channels or the presence of channels or the presence of channels with different open probabilities. However, the current trace sometimes exhibits single transitions spanning several levels. Since the probability of simultaneous transitions of independent channels is infinitesimally small, such observations strongly suggest a cooperative gating behavior. We present a Markov model to describe the cooperative gating of channels using only the all-points current amplitude histograms for the probability of observing the various conductance levels. We investigate the steady-state (or equilibrium) properties of a system of N channels and provide a scheme to express all the probabilities in terms of just two parameters. The main feature of our model is that lateral interaction of channels gives rise to cooperative gating. Another useful feature is the introduction of the language of graph theory which can potentially provide a different avenue to study ion channel kinetics. We write down explicit expressions for systems of two, three and four channels and provide a procedure to describe the system of N channels.

  17. Genomic mining of prokaryotic repressors for orthogonal logic gates.

    Science.gov (United States)

    Stanton, Brynne C; Nielsen, Alec A K; Tamsir, Alvin; Clancy, Kevin; Peterson, Todd; Voigt, Christopher A

    2014-02-01

    Genetic circuits perform computational operations based on interactions between freely diffusing molecules within a cell. When transcription factors are combined to build a circuit, unintended interactions can disrupt its function. Here, we apply 'part mining' to build a library of 73 TetR-family repressors gleaned from prokaryotic genomes. The operators of a subset were determined using an in vitro method, and this information was used to build synthetic promoters. The promoters and repressors were screened for cross-reactions. Of these, 16 were identified that both strongly repress their cognate promoter (5- to 207-fold) and exhibit minimal interactions with other promoters. Each repressor-promoter pair was converted to a NOT gate and characterized. Used as a set of 16 NOT/NOR gates, there are >10(54) circuits that could be built by changing the pattern of input and output promoters. This represents a large set of compatible gates that can be used to construct user-defined circuits.

  18. Gate control of spin-polarized conductance in alloyed transitional metal nanocontacts

    Science.gov (United States)

    Sivkov, Ilia N.; Brovko, Oleg O.; Rungger, Ivan; Stepanyuk, Valeri S.

    2017-03-01

    To date, endeavors in nanoscale spintronics are dominated by the use of single-electron or single-spin transistors having at their heart a semiconductor, metallic, or molecular quantum dot whose localized states are non-spin-degenerate and can be controlled by an external bias applied via a gate electrode. Adjusting the bias of the gate one can realign those states with respect to the chemical potentials of the leads and thus tailor the spin-polarized transmission properties of the device. Here we show that similar functionality can be achieved in a purely metallic junction comprised of a metallic magnetic chain attached to metallic paramagnetic leads and biased by a gate electrode. Our ab initio calculations of electron transport through mixed Pt-Fe (Fe-Pd and Fe-Rh) atomic chains suspended between Pt (Pd and Rh) electrodes show that spin-polarized confined states of the chain can be shifted by the gate bias causing a change in the relative contributions of majority and minority channels to the nanocontact's conductance. As a result, we observe strong dependence of conductance spin polarization on the applied gate potential. In some cases the spin polarization of conductance can even be reversed in sign upon gate potential application, which is a remarkable and promising trait for spintronic applications.

  19. Gate-tunable phase transitions in thin flakes of 1T-TaS2

    Science.gov (United States)

    Yu, Yijun; Yang, Fangyuan; Lu, Xiu Fang; Yan, Ya Jun; Cho, Yong-Heum; Ma, Liguo; Niu, Xiaohai; Kim, Sejoong; Son, Young-Woo; Feng, Donglai; Li, Shiyan; Cheong, Sang-Wook; Chen, Xian Hui; Zhang, Yuanbo

    2015-03-01

    The ability to tune material properties using gating by electric fields is at the heart of modern electronic technology. It is also a driving force behind recent advances in two-dimensional systems, such as the observation of gate electric-field-induced superconductivity and metal-insulator transitions. Here, we describe an ionic field-effect transistor (termed an iFET), in which gate-controlled Li ion intercalation modulates the material properties of layered crystals of 1T-TaS2. The strong charge doping induced by the tunable ion intercalation alters the energetics of various charge-ordered states in 1T-TaS2 and produces a series of phase transitions in thin-flake samples with reduced dimensionality. We find that the charge-density wave states in 1T-TaS2 collapse in the two-dimensional limit at critical thicknesses. Meanwhile, at low temperatures, the ionic gating induces multiple phase transitions from Mott-insulator to metal in 1T-TaS2 thin flakes, with five orders of magnitude modulation in resistance, and superconductivity emerges in a textured charge-density wave state induced by ionic gating. Our method of gate-controlled intercalation opens up possibilities in searching for novel states of matter in the extreme charge-carrier-concentration limit.

  20. Strongly interacting Fermi gases

    Directory of Open Access Journals (Sweden)

    Bakr W.

    2013-08-01

    Full Text Available Strongly interacting gases of ultracold fermions have become an amazingly rich test-bed for many-body theories of fermionic matter. Here we present our recent experiments on these systems. Firstly, we discuss high-precision measurements on the thermodynamics of a strongly interacting Fermi gas across the superfluid transition. The onset of superfluidity is directly observed in the compressibility, the chemical potential, the entropy, and the heat capacity. Our measurements provide benchmarks for current many-body theories on strongly interacting fermions. Secondly, we have studied the evolution of fermion pairing from three to two dimensions in these gases, relating to the physics of layered superconductors. In the presence of p-wave interactions, Fermi gases are predicted to display toplogical superfluidity carrying Majorana edge states. Two possible avenues in this direction are discussed, our creation and direct observation of spin-orbit coupling in Fermi gases and the creation of fermionic molecules of 23Na 40K that will feature strong dipolar interactions in their absolute ground state.

  1. Strong Little Magnets

    Science.gov (United States)

    Moloney, Michael J.

    2007-01-01

    Did you know that some strong little cylindrical magnets available in local hardware stores can have an effective circumferential current of 2500 A? This intriguing information can be obtained by hanging a pair of magnets at the center of a coil, as shown in Fig. 1, and measuring the oscillation frequency as a function of coil current.

  2. Materials Fundamentals of Gate Dielectrics

    CERN Document Server

    Demkov, Alexander A

    2006-01-01

    This book presents materials fundamentals of novel gate dielectrics that are being introduced into semiconductor manufacturing to ensure the continuous scalling of the CMOS devices. This is a very fast evolving field of research so we choose to focus on the basic understanding of the structure, thermodunamics, and electronic properties of these materials that determine their performance in device applications. Most of these materials are transition metal oxides. Ironically, the d-orbitals responsible for the high dielectric constant cause sever integration difficulties thus intrinsically limiting high-k dielectrics. Though new in the electronics industry many of these materials are wel known in the field of ceramics, and we describe this unique connection. The complexity of the structure-property relations in TM oxides makes the use of the state of the art first-principles calculations necessary. Several chapters give a detailed description of the modern theory of polarization, and heterojunction band discont...

  3. Ryanodine receptor gating controls generation of diastolic calcium waves in cardiac myocytes

    Science.gov (United States)

    Petrovič, Pavol; Valent, Ivan; Cocherová, Elena; Pavelková, Jana

    2015-01-01

    The role of cardiac ryanodine receptor (RyR) gating in the initiation and propagation of calcium waves was investigated using a mathematical model comprising a stochastic description of RyR gating and a deterministic description of calcium diffusion and sequestration. We used a one-dimensional array of equidistantly spaced RyR clusters, representing the confocal scanning line, to simulate the formation of calcium sparks. Our model provided an excellent description of the calcium dependence of the frequency of diastolic calcium sparks and of the increased tendency for the production of calcium waves after a decrease in cytosolic calcium buffering. We developed a hypothesis relating changes in the propensity to form calcium waves to changes of RyR gating and tested it by simulation. With a realistic RyR gating model, increased ability of RyR to be activated by Ca2+ strongly increased the propensity for generation of calcium waves at low (0.05–0.1-µM) calcium concentrations but only slightly at high (0.2–0.4-µM) calcium concentrations. Changes in RyR gating altered calcium wave formation by changing the calcium sensitivity of spontaneous calcium spark activation and/or the average number of open RyRs in spontaneous calcium sparks. Gating changes that did not affect RyR activation by Ca2+ had only a weak effect on the propensity to form calcium waves, even if they strongly increased calcium spark frequency. Calcium waves induced by modulating the properties of the RyR activation site could be suppressed by inhibiting the spontaneous opening of the RyR. These data can explain the increased tendency for production of calcium waves under conditions when RyR gating is altered in cardiac diseases. PMID:26009544

  4. Graduate Automotive Technology Education (GATE) Center

    Energy Technology Data Exchange (ETDEWEB)

    Jeffrey Hodgson; David Irick

    2005-09-30

    The Graduate Automotive Technology Education (GATE) Center at the University of Tennessee, Knoxville has completed its sixth year of operation. During this period the Center has involved thirteen GATE Fellows and ten GATE Research Assistants in preparing them to contribute to advanced automotive technologies in the center's focus area: hybrid drive trains and control systems. Eighteen GATE students have graduated, and three have completed their course work requirements. Nine faculty members from three departments in the College of Engineering have been involved in the GATE Center. In addition to the impact that the Center has had on the students and faculty involved, the presence of the center has led to the acquisition of resources that probably would not have been obtained if the GATE Center had not existed. Significant industry interaction such as internships, equipment donations, and support for GATE students has been realized. The value of the total resources brought to the university (including related research contracts) exceeds $4,000,000. Problem areas are discussed in the hope that future activities may benefit from the operation of the current program.

  5. Strong Field Spherical Dynamos

    CERN Document Server

    Dormy, Emmanuel

    2014-01-01

    Numerical models of the geodynamo are usually classified in two categories: those denominated dipolar modes, observed when the inertial term is small enough, and multipolar fluctuating dynamos, for stronger forcing. I show that a third dynamo branch corresponding to a dominant force balance between the Coriolis force and the Lorentz force can be produced numerically. This force balance is usually referred to as the strong field limit. This solution co-exists with the often described viscous branch. Direct numerical simulations exhibit a transition from a weak-field dynamo branch, in which viscous effects set the dominant length scale, and the strong field branch in which viscous and inertial effects are largely negligible. These results indicate that a distinguished limit needs to be sought to produce numerical models relevant to the geodynamo and that the usual approach of minimizing the magnetic Prandtl number (ratio of the fluid kinematic viscosity to its magnetic diffusivity) at a given Ekman number is mi...

  6. Computing Symmetric Boolean Functions by Circuits with Few Exact Threshold Gates

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt

    2007-01-01

    We consider constant depth circuits augmented with few exact threshold gates with arbitrary weights. We prove strong (up to exponential) size lower bounds for such circuits computing symmetric Boolean functions. Our lower bound is expressed in terms of a natural parameter, the balance, of symmetric...

  7. Strongly Correlated Materials

    OpenAIRE

    Morosan, Emilia; Natelson, Douglas; Nevidomskyy, Andriy H.; Si, Qimiao

    2013-01-01

    Strongly correlated materials are profoundly affected by the repulsive electron-electron interaction. This stands in contrast to many commonly used materials such as silicon and aluminum, whose properties are comparatively unaffected by the Coulomb repulsion. Correlated materials often have remarkable properties and transitions between distinct, competing phases with dramatically different electronic and magnetic orders. These rich phenomena are fascinating from the basic science perspective ...

  8. Open Flavor Strong Decays

    Science.gov (United States)

    García-Tecocoatzi, H.; Bijker, R.; Ferretti, J.; Galatà, G.; Santopinto, E.

    2016-10-01

    In this contribution, we discuss the results of a QM calculation of the open-flavor strong decays of **** light nucleon resonances. These are the results of a recent calculation, where we used a modified ^3P_0 model for the amplitudes and the U(7) algebraic model and the hypercentral quark model to predict the baryon spectrum. The decay amplitudes are compared with the existing experimental data.

  9. Strongly Correlated Topological Insulators

    Science.gov (United States)

    2016-02-03

    Research Triangle Park , NC 27709-2211 Condensed Matter, Topological Phases of Matter REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER(S...Strongly Correlated Topological Insulators In the past year, the grant was used for work in the field of topological phases, with emphasis on finding...surface of topological insulators. In the past 3 years, we have started a new direction, that of fractional topological insulators. These are materials

  10. Strong Coupling and Classicalization

    CERN Document Server

    Dvali, Gia

    2016-01-01

    Classicalization is a phenomenon in which a theory prevents itself from entering into a strong-coupling regime, by redistributing the energy among many weakly-interacting soft quanta. In this way, the scattering process of some initial hard quanta splits into a large number of soft elementary processes. In short, the theory trades the strong coupling for a high-multiplicity of quanta. At very high energies, the outcome of such a scattering experiment is a production of soft states of high occupation number that are approximately classical. It is evident that black hole creation in particle collision at super-Planckian energies is a result of classicalization, but there is no a priory reason why this phenomenon must be limited to gravity. If the hierarchy problem is solved by classicalization, the LHC has a chance of detecting a tower of new resonances. The lowest-lying resonances must appear right at the strong coupling scale in form of short-lived elementary particles. The heavier members of the tower must b...

  11. A quantum Fredkin gate (Conference Presentation)

    Science.gov (United States)

    Patel, Raj B.; Ho, Joseph; Ferreyrol, Franck; Ralph, Timothy C.; Pryde, Geoff J.

    2016-10-01

    One of the greatest challenges in modern science is the realisation of quantum computers which, as their scale increases, will allow enhanced performance of tasks across many areas of quantum information processing. Quantum logic gates play a vital role in realising these applications by carrying out the elementary operations on the qubits; a key aim is minimising the resources needed to build these gates into useful circuits. While the salient features of a quantum computer have been shown in proof-of-principle experiments, e.g., single- and two-qubit gates, difficulties in scaling quantum systems to encode and manipulate multiple qubits has hindered demonstrations of more complex operations. This is exemplified by the classical Fredkin (or controlled-SWAP) gate [1] for which, despite many theoretical proposals [2,3] relying on concatenating multiple two-qubit gates, a quantum analogue has yet to be realised. Here, by directly adding control to a two-qubit SWAP unitary [4], we use photonic qubit logic to report the first experimental demonstration of a quantum Fredkin gate [5]. Our scheme uses linear optics and improves on the overall probability of success by an order of magnitude over previous proposals [2,3]. This optical approach allows us to add control an arbitrary black-box unitary which is otherwise forbidden in the standard circuit model [6]. Additionally, the action of our gate exhibits quantum coherence allowing the generation of the highest fidelity three-photon GHZ states to date. The quantum Fredkin gate has many applications in quantum computing, quantum measurements [7] and cryptography [8,9]. Using our scheme, we apply the Fredkin gate to the task of direct measurements of the purity and state overlap of a quantum system [7] without recourse to quantum state tomography.

  12. Impact of phosphomimetic and non-phosphorylatable mutations of phospholemman on L-type calcium channels gating in HEK 293T cells.

    Science.gov (United States)

    Guo, Kai; Wang, Yue-Peng; Zhou, Zhi-Wen; Jiang, Yi-Bo; Li, Wei; Chen, Xiao-Meng; Li, Yi-Gang

    2015-03-01

    Phospholemman (PLM) is an important phosphorylation substrate for protein kinases A and C in the heart. Until now, the association between PLM phosphorylation status and L-type calcium channels (LTCCs) gating has not been fully understood. We investigated the kinetics of LTCCs in HEK 293T cells expressing phosphomimetic or nonphosphorylatable PLM mutants. The LTCCs gating was measured in HEK 293T cells transfected with LTCC and wild-type (WT) PLM, phosphomimetic or nonphosphorylatable PLM mutants: 6263AA, 6869AA, AAAA, 6263DD, 6869DD or DDDD. WT PLM significantly slowed LTCCs activation and deactivation while enhanced voltage-dependent inactivation (VDI). PLM mutants 6869DD and DDDD significantly increased the peak of the currents. 6263DD accelerated channel activation, while 6263AA slowed it more than WT PLM. 6869DD significantly enhanced PLM-induced increase of VDI. AAAA slowed the channel activation more than 6263AA, and DDDD accelerated the channel VDI more than 6869DD. Our results demonstrate that phosphomimetic PLM could stimulate LTCCs and alter their dynamics, while PLM nonphosphorylatable mutant produced the opposite effects. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. Neuroprotective effect of interleukin-6 regulation of voltage-gated Na+ channels of cortical neurons is time- and dose-dependent

    Directory of Open Access Journals (Sweden)

    Wei Xia

    2015-01-01

    Full Text Available Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours by studying voltage-gated Na + channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na + currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na + channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

  14. Neuroprotective effect of interleukin-6 regulation of voltage-gated Na(+) channels of cortical neurons is time- and dose-dependent.

    Science.gov (United States)

    Xia, Wei; Peng, Guo-Yi; Sheng, Jiang-Tao; Zhu, Fang-Fang; Guo, Jing-Fang; Chen, Wei-Qiang

    2015-04-01

    Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL) and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours) by studying voltage-gated Na(+) channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na(+) currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na(+) channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

  15. Neuroprotective effect of interleukin-6 regulation of voltage-gated Na+ channels of cortical neurons is time- and dose-dependent

    Institute of Scientific and Technical Information of China (English)

    Wei Xia; Guo-yi Peng; Jiang-tao Sheng; Fang-fang Zhu; Jing-fang Guo; Wei-qiang Chen

    2015-01-01

    Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour expo-sure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL) and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours) by studying voltage-gated Na+ channels using a patch-clamp technique. Volt-age-clamp recording results demonstrated that interleukin-6 suppressed Na+ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na+channels in rat corti-cal neurons by interleukin-6 is time- and dose-dependent.

  16. Getting started with FortiGate

    CERN Document Server

    Fabbri, Rosato

    2013-01-01

    This book is a step-by-step tutorial that will teach you everything you need to know about the deployment and management of FortiGate, including high availability, complex routing, various kinds of VPN working, user authentication, security rules and controls on applications, and mail and Internet access.This book is intended for network administrators, security managers, and IT pros. It is a great starting point if you have to administer or configure a FortiGate unit, especially if you have no previous experience. For people that have never managed a FortiGate unit, the book helpfully walks t

  17. Gate A: changes to opening hours

    CERN Multimedia

    2015-01-01

    Due to maintenance work, the opening hours of Gate A (near Reception) will be modified between Monday, 13 and Friday, 17 April 2015.   During this period, the gate will be open to vehicles between 7 a.m. and 9.30 a.m., then between 4.30 p.m. and 7 p.m. It will be completely closed to traffic between 9.30 a.m. and 4.30 p.m. Pedestrians and cyclists may continue to use the gate. We apologise for any inconvenience and thank you for your understanding.

  18. Diagonal gates in the Clifford hierarchy

    Science.gov (United States)

    Cui, Shawn X.; Gottesman, Daniel; Krishna, Anirudh

    2017-01-01

    The Clifford hierarchy is a set of gates that appears in the theory of fault-tolerant quantum computation, but its precise structure remains elusive. We give a complete characterization of the diagonal gates in the Clifford hierarchy for prime-dimensional qudits. They turn out to be pmth roots of unity raised to polynomial functions of the basis state to which they are applied, and we determine which level of the Clifford hierarchy a given gate sits in based on m and the degree of the polynomial.

  19. Calibration of submerged multi-sluice gates

    Directory of Open Access Journals (Sweden)

    Mohamed F. Sauida

    2014-09-01

    The main objective of this work is to study experimentally and verify empirically the different parameters affecting the discharge through submerged multiple sluice gates (i.e., the expansion ratios, gates operational management, etc.. Using multiple regression analysis of the experimental results, a general equation for discharge coefficient is developed. The results show, that the increase in the expansion ratio and the asymmetric operation of gates, give higher values for the discharge coefficient. The obtained predictions of the discharge coefficient using the developed equations are compared to the experimental data. The present developed equations showed good consistency and high accuracy.

  20. Stay vane and wicket gate relationship study

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2005-01-19

    This report evaluates potential environmental and performance gains that can be achieved in a Kaplan turbine through non-structural modifications to stay vane and wicket gate assemblies. This summary is based primarily on data and conclusions drawn from models and studies of Lower Granite Dam. Based on this investigation, the study recommends (1) a proof of concept at Lower Granite Dam to establish predicted improvements for the existing turbine and to further refine the stay vane wicket gate designs for fish passage; and (2) consideration of the stay vane wicket gate systems in any future turbine rehabilitation studies.

  1. Cascaded logic gates in nanophotonic plasmon networks.

    Science.gov (United States)

    Wei, Hong; Wang, Zhuoxian; Tian, Xiaorui; Käll, Mikael; Xu, Hongxing

    2011-07-12

    Optical computing has been pursued for decades as a potential strategy for advancing beyond the fundamental performance limitations of semiconductor-based electronic devices, but feasible on-chip integrated logic units and cascade devices have not been reported. Here we demonstrate that a plasmonic binary NOR gate, a 'universal logic gate', can be realized through cascaded OR and NOT gates in four-terminal plasmonic nanowire networks. This finding provides a path for the development of novel nanophotonic on-chip processor architectures for future optical computing technologies.

  2. The gating of the CFTR channel.

    Science.gov (United States)

    Moran, Oscar

    2017-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel expressed in the apical membrane of epithelia. Mutations in the CFTR gene are the cause of cystsic fibrosis. CFTR is the only ABC-protein that constitutes an ion channel pore forming subunit. CFTR gating is regulated in complex manner as phosphorylation is mandatory for channel activity and gating is directly regulated by binding of ATP to specific intracellular sites on the CFTR protein. This review covers our current understanding on the gating mechanism in CFTR and illustrates the relevance of alteration of these mechanisms in the onset of cystic fibrosis.

  3. A STRONG LINK

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Trade frictions should not affect the mainstream of Sino-U.S. mutually beneficial economic and trade cooperation China and the United States have a complicated relationship, one that can be called a competitive partnership. The U.S. trade deficit with China, its third largest trading partner, hit a staggering $201.6 billion last year, an imbalance that is a major bone of contention. Yet, while frictions over trade, intellectual property rights and other issues grab the headlines, there is strong-and grow...

  4. Analysis and Design of Tri-Gate MOSFET with High Dielectrics Gate

    Directory of Open Access Journals (Sweden)

    Viranjay M. Srivastava

    2012-05-01

    Full Text Available The scaling of simple gate transistors requires the scaling and transistor elements like source/drain junction became difficult to scale further after a limit due to adverse effect of electrostatic and short-channel performance. The solution of the problem is tri-gate where we can increase the performance without increasing the width and without scaling. In this paper we have described the parameter of tri-gate and taking the high dielectric as substrate.

  5. β-Adrenergic receptor agonist increases voltage-gated Na(+) currents in medial prefrontal cortex pyramidal neurons.

    Science.gov (United States)

    Szulczyk, Bartlomiej

    2015-05-19

    The prefrontal cortex does not function properly in neuropsychiatric diseases and during chronic stress. The aim of this study was to test the effects of isoproterenol, a β-adrenergic receptor agonist, on the voltage-dependent fast-inactivating Na(+) currents in medial prefrontal cortex (mPFC) pyramidal neurons obtained from young rats. The recordings were performed in the cell-attached configuration. Isoproterenol (2μM) did not change the peak Na(+) current amplitude but shifted the IV curve of the Na(+) currents toward hyperpolarization. Pretreatment of the cells with the β-adrenergic antagonists propranolol and metoprolol abolished the effect of isoproterenol on the Na(+) currents, suggesting the involvement of β1-adrenergic receptors. The effect of β-adrenergic receptor stimulation on the sodium currents was dependent on kinase A and kinase C; the effect was diminished in the presence of the kinase A antagonist H-89 and the kinase C antagonist chelerythrine and abolished when the antagonists were coapplied. Moreover, isoproterenol depolarized the membrane potential recorded using the perforated-patch method, and this depolarization was abolished by cesium ions. Thus, in mPFC pyramidal neurons, stimulation of β-adrenergic receptors up-regulates the fast-inactivating voltage-gated Na(+) currents evoked by suprathreshold depolarizations.

  6. Strongly correlated materials.

    Science.gov (United States)

    Morosan, Emilia; Natelson, Douglas; Nevidomskyy, Andriy H; Si, Qimiao

    2012-09-18

    Strongly correlated materials are profoundly affected by the repulsive electron-electron interaction. This stands in contrast to many commonly used materials such as silicon and aluminum, whose properties are comparatively unaffected by the Coulomb repulsion. Correlated materials often have remarkable properties and transitions between distinct, competing phases with dramatically different electronic and magnetic orders. These rich phenomena are fascinating from the basic science perspective and offer possibilities for technological applications. This article looks at these materials through the lens of research performed at Rice University. Topics examined include: Quantum phase transitions and quantum criticality in "heavy fermion" materials and the iron pnictide high temperature superconductors; computational ab initio methods to examine strongly correlated materials and their interface with analytical theory techniques; layered dichalcogenides as example correlated materials with rich phases (charge density waves, superconductivity, hard ferromagnetism) that may be tuned by composition, pressure, and magnetic field; and nanostructure methods applied to the correlated oxides VO₂ and Fe₃O₄, where metal-insulator transitions can be manipulated by doping at the nanoscale or driving the system out of equilibrium. We conclude with a discussion of the exciting prospects for this class of materials.

  7. Strong Coupling Holography

    CERN Document Server

    Dvali, Gia

    2009-01-01

    We show that whenever a 4-dimensional theory with N particle species emerges as a consistent low energy description of a 3-brane embedded in an asymptotically-flat (4+d)-dimensional space, the holographic scale of high-dimensional gravity sets the strong coupling scale of the 4D theory. This connection persists in the limit in which gravity can be consistently decoupled. We demonstrate this effect for orbifold planes, as well as for the solitonic branes and string theoretic D-branes. In all cases the emergence of a 4D strong coupling scale from bulk holography is a persistent phenomenon. The effect turns out to be insensitive even to such extreme deformations of the brane action that seemingly shield 4D theory from the bulk gravity effects. A well understood example of such deformation is given by large 4D Einstein term in the 3-brane action, which is known to suppress the strength of 5D gravity at short distances and change the 5D Newton's law into the four-dimensional one. Nevertheless, we observe that the ...

  8. Involvement of the S4-S5 linker and the C-linker domain regions to voltage-gating in plant Shaker channels: comparison with animal HCN and Kv channels.

    Science.gov (United States)

    Nieves-Cordones, Manuel; Gaillard, Isabelle

    2014-01-01

    Among the different transport systems present in plant cells, Shaker channels constitute the major pathway for K(+) in the plasma membrane. Plant Shaker channels are members of the 6 transmembrane-1 pore (6TM-1P) cation channel superfamily as the animal Shaker (Kv) and HCN channels. All these channels are voltage-gated K(+) channels: Kv channels are outward-rectifiers, opened at depolarized voltages and HCN channels are inward-rectifiers, opened by membrane hyperpolarization. Among plant Shaker channels, we can find outward-rectifiers, inward-rectifiers and also weak-rectifiers, with weak voltage dependence. Despite the absence of crystal structures of plant Shaker channels, functional analyses coupled to homology modeling, mostly based on Kv and HCN crystals, have permitted the identification of several regions contributing to plant Shaker channel gating. In the present mini-review, we make an update on the voltage-gating mechanism of plant Shaker channels which seem to be comparable to that proposed for HCN channels.

  9. Active gated imaging in driver assistance system

    Science.gov (United States)

    Grauer, Yoav

    2014-04-01

    In this paper, we shall present the active gated imaging system (AGIS) in relation to the automotive field. AGIS is based on a fast-gated camera and pulsed illuminator, synchronized in the time domain to record images of a certain range of interest. A dedicated gated CMOS imager sensor and near infra-red (NIR) pulsed laser illuminator, is presented in this paper to provide active gated technology. In recent years, we have developed these key components and learned the system parameters, which are most beneficial to nighttime (in all weather conditions) driving in terms of field of view, illumination profile, resolution, and processing power. We shall present our approach of a camera-based advanced driver assistance systems (ADAS) named BrightEye™, which makes use of the AGIS technology in the automotive field.

  10. Single spin universal Boolean logic gate

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, H; Pramanik, S; Bandyopadhyay, S [Department of Electrical and Computer Engineering, Virginia Commonwealth University, Richmond, VA 23284 (United States)

    2008-01-15

    Recent advances in manipulating single electron spins in quantum dots have brought us close to the realization of classical logic gates, where binary bits are encoded in spin polarizations of single electrons. Here, we show that a linear array of three quantum dots, each containing a single spin polarized electron, and with nearest neighbor exchange coupling, acts as a NAND gate. The energy dissipated during switching this gate is the Landauer-Shannon limit of kTln(1/p{sub i} ) (T = ambient temperature and p{sub i}= intrinsic gate error probability). With present day technology, p{sub i} = 10{sup -9} is achievable above 1 K temperature. Even with this small intrinsic error probability, the energy dissipated during switching is only {approx}21kT, while today's nanoscale transistors dissipate about 40 000-50 000kT when they switch.

  11. Adiabatic quantum gates and Boolean functions

    Energy Technology Data Exchange (ETDEWEB)

    Andrecut, M; Ali, M K [Department of Physics, University of Lethbridge, Lethbridge, AB, T1K 3M4 (Canada)

    2004-06-25

    We discuss the logical implementation of quantum gates and Boolean functions in the framework of quantum adiabatic method, which uses the language of ground states, spectral gaps and Hamiltonians instead of the standard unitary transformation language. (letter to the editor)

  12. Synthesizing biomolecule-based Boolean logic gates.

    Science.gov (United States)

    Miyamoto, Takafumi; Razavi, Shiva; DeRose, Robert; Inoue, Takanari

    2013-02-15

    One fascinating recent avenue of study in the field of synthetic biology is the creation of biomolecule-based computers. The main components of a computing device consist of an arithmetic logic unit, the control unit, memory, and the input and output devices. Boolean logic gates are at the core of the operational machinery of these parts, and hence to make biocomputers a reality, biomolecular logic gates become a necessity. Indeed, with the advent of more sophisticated biological tools, both nucleic acid- and protein-based logic systems have been generated. These devices function in the context of either test tubes or living cells and yield highly specific outputs given a set of inputs. In this review, we discuss various types of biomolecular logic gates that have been synthesized, with particular emphasis on recent developments that promise increased complexity of logic gate circuitry, improved computational speed, and potential clinical applications.

  13. Coherently dedispersed gated imaging of millisecond pulsars

    CERN Document Server

    Roy, Jayanta

    2013-01-01

    Motivated by the need for rapid localisation of newly discovered faint millisecond pulsars (MSPs) we have developed a coherently dedispersed gating correlator. This gating correlator accounts for the orbital motions of MSPs in binaries while folding the visibilities with best-fit topocentric rotational model derived from periodicity search in simultaneously generated beamformer output. Unique applications of the gating correlator for sensitive interferometric studies of MSPs are illustrated using the Giant Metrewave Radio Telescope (GMRT) interferometric array. We could unambiguously localise five newly discovered Fermi MSPs in the on-off gated image plane with an accuracy of +-1". Immediate knowledge of such precise position allows the use of sensitive coherent beams of array telescopes for follow-up timing observations, which substantially reduces the use of telescope time (~ 20X for the GMRT). In addition, precise a-priori astrometric position reduces the effect of large covariances in timing fit (with dis...

  14. Golden Gate and Pt. Reyes Acoustic Detections

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset contains detections of acoustic tagged fish from two general locations: Golden Gate (east and west line) and Pt. Reyes. Several Vemco 69khz acoustic...

  15. 2010 ARRA Lidar: Golden Gate (CA)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Golden Gate LiDAR Project is a cooperative project sponsored by the US Geological Survey (USGS) and San Francisco State University (SFSU) that has resulted in...

  16. Time-gated optical projection tomography.

    Science.gov (United States)

    Bassi, Andrea; Brida, Daniele; D'Andrea, Cosimo; Valentini, Gianluca; Cubeddu, Rinaldo; De Silvestri, Sandro; Cerullo, Giulio

    2010-08-15

    We present an imaging technique that combines optical projection tomography with ballistic imaging using ultrafast time gating. The method provides high-resolution reconstruction of scattering samples and is suitable for three-dimensional (3D) imaging of biological models.

  17. Single gate optimization for plastic injection mold

    Institute of Scientific and Technical Information of China (English)

    LI Ji-quan; LI De-qun; GUO Zhi-ying; LV Hai-yuan

    2007-01-01

    This paper deals with a methodology for single gate location optimization for plastic injection mold. The objective of the gate optimization is to minimize the warpage of injection molded parts, because warpage is a crucial quality issue for most injection molded parts while it is influenced greatly by the gate location. Feature warpage is defined as the ratio of maximum displacement on the feature surface to the projected length of the feature surface to describe part warpage. The optimization is combined with the numerical simulation technology to find the optimal gate location, in which the simulated annealing algorithm is used to search for the optimum. Finally, an example is discussed in the paper and it can be concluded that the proposed method is effective.

  18. GATING SYSTEMS FOR PRODUCTION OF HYDRODISTRIBUTORS

    Directory of Open Access Journals (Sweden)

    D. A. Volkov

    2010-01-01

    Full Text Available Gating systems of the first group of special ways of casting into shell molds, casting in lined chill mold as more effective for production of hydrodistributors were developed and studied.

  19. Mechanical gating of a mechanochemical reaction cascade

    Science.gov (United States)

    Wang, Junpeng; Kouznetsova, Tatiana B.; Boulatov, Roman; Craig, Stephen L.

    2016-11-01

    Covalent polymer mechanochemistry offers promising opportunities for the control and engineering of reactivity. To date, covalent mechanochemistry has largely been limited to individual reactions, but it also presents potential for intricate reaction systems and feedback loops. Here we report a molecular architecture, in which a cyclobutane mechanophore functions as a gate to regulate the activation of a second mechanophore, dichlorocyclopropane, resulting in a mechanochemical cascade reaction. Single-molecule force spectroscopy, pulsed ultrasonication experiments and DFT-level calculations support gating and indicate that extra force of >0.5 nN needs to be applied to a polymer of gated gDCC than of free gDCC for the mechanochemical isomerization gDCC to proceed at equal rate. The gating concept provides a mechanism by which to regulate stress-responsive behaviours, such as load-strengthening and mechanochromism, in future materials designs.

  20. Low-temperature electronic transport measurements on a gated delta -doped GaAs sample: magnetoresistance, quantum Hall effect and conductivity fluctuations

    OpenAIRE

    Dötzer, R.; Friedland, K. J.; Hey, R.; Kostial, H; Miehling, H.; Schoepe, Wilfried

    1994-01-01

    We present magnetotransport measurements (up to 7 T) performed at very low temperatures (down to 20 mK) on a GaAs sample containing two parallel delta -doped layers whose carrier concentration can be varied by means of a gate electrode. With increasing negative gate voltage the resistance becomes more strongly temperature-dependent, indicating a more localized electron system. The magnetoresistance is found to be strongly anisotropic. When the field is parallel to the layers we find a large p...

  1. Optimized Multiplier Using Reversible Multicontrol Input Toffoli Gates

    Directory of Open Access Journals (Sweden)

    H R Bhagyalakshmi

    2013-01-01

    Full Text Available Reversible logic is an important area to carry the computation into the world of quantum computing. In thispaper a 4-bit multiplier using a new reversible logic gate called BVPPG gate is presented. BVPPG gate isa 5 x 5 reversible gate which is designed to generate partial products required to perform multiplicationand also duplication of operand bits is obtained. This reduces the total cost of the circuit. Toffoli gate isthe universal and also most flexible reversible logic gate. So we have used the Toffoli gates to construct thedesigned multiplier.

  2. Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels.

    Science.gov (United States)

    Zhang, Guohui; Geng, Yanyan; Jin, Yakang; Shi, Jingyi; McFarland, Kelli; Magleby, Karl L; Salkoff, Lawrence; Cui, Jianmin

    2017-03-06

    Large conductance Ca(2+)-activated K(+) channels (BK channels) gate open in response to both membrane voltage and intracellular Ca(2+) The channel is formed by a central pore-gate domain (PGD), which spans the membrane, plus transmembrane voltage sensors and a cytoplasmic gating ring that acts as a Ca(2+) sensor. How these voltage and Ca(2+) sensors influence the common activation gate, and interact with each other, is unclear. A previous study showed that a BK channel core lacking the entire cytoplasmic gating ring (Core-MT) was devoid of Ca(2+) activation but retained voltage sensitivity (Budelli et al. 2013. Proc. Natl. Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1313433110). In this study, we measure voltage sensor activation and pore opening in this Core-MT channel over a wide range of voltages. We record gating currents and find that voltage sensor activation in this truncated channel is similar to WT but that the coupling between voltage sensor activation and gating of the pore is reduced. These results suggest that the gating ring, in addition to being the Ca(2+) sensor, enhances the effective coupling between voltage sensors and the PGD. We also find that removal of the gating ring alters modulation of the channels by the BK channel's β1 and β2 subunits.

  3. Electrical manipulation of spin states in a single electrostatically gated transition-metal complex

    DEFF Research Database (Denmark)

    Osorio, Edgar A; Moth-Poulsen, Kasper; van der Zant, Herre S J;

    2010-01-01

    We demonstrate an electrically controlled high-spin (S = 5/2) to low-spin (S = 1/2) transition in a three-terminal device incorporating a single Mn(2+) ion coordinated by two terpyridine ligands. By adjusting the gate-voltage we reduce the terpyridine moiety and thereby strengthen the ligand...... a strongly gate-dependent singlet-triplet splitting on the low-spin side. The measured bias-spectroscopy is shown to be consistent with an exact diagonalization of the Mn-complex, and an interpretation of the data is given in terms of a simplified effective model....

  4. P50 sensory gating in infants.

    Science.gov (United States)

    Ross, Anne Spencer; Hunter, Sharon Kay; Groth, Mark A; Ross, Randal Glenn

    2013-12-26

    Attentional deficits are common in a variety of neuropsychiatric disorders including attention deficit-hyperactivity disorder, autism, bipolar mood disorder, and schizophrenia. There has been increasing interest in the neurodevelopmental components of these attentional deficits; neurodevelopmental meaning that while the deficits become clinically prominent in childhood or adulthood, the deficits are the results of problems in brain development that begin in infancy or even prenatally. Despite this interest, there are few methods for assessing attention very early in infancy. This report focuses on one method, infant auditory P50 sensory gating. Attention has several components. One of the earliest components of attention, termed sensory gating, allows the brain to tune out repetitive, noninformative sensory information. Auditory P50 sensory gating refers to one task designed to measure sensory gating using changes in EEG. When identical auditory stimuli are presented 500 ms apart, the evoked response (change in the EEG associated with the processing of the click) to the second stimulus is generally reduced relative to the response to the first stimulus (i.e. the response is "gated"). When response to the second stimulus is not reduced, this is considered a poor sensory gating, is reflective of impaired cerebral inhibition, and is correlated with attentional deficits. Because the auditory P50 sensory gating task is passive, it is of potential utility in the study of young infants and may provide a window into the developmental time course of attentional deficits in a variety of neuropsychiatric disorders. The goal of this presentation is to describe the methodology for assessing infant auditory P50 sensory gating, a methodology adapted from those used in studies of adult populations.

  5. Cognitive mechanisms associated with auditory sensory gating

    OpenAIRE

    Jones, L. A.; Hills, P.J.; Dick, K.M.; Jones, S. P.; Bright, P

    2015-01-01

    Sensory gating is a neurophysiological measure of inhibition that is characterised by a reduction in the P50 event-related potential to a repeated identical stimulus. The objective of this work was to determine the cognitive mechanisms that relate to the neurological phenomenon of auditory sensory gating. Sixty participants underwent a battery of 10 cognitive tasks, including qualitatively different measures of attentional inhibition, working memory, and fluid intelligence. Participants addit...

  6. Molecular Model of Anticonvulsant Drug Binding to the Voltage-Gated Sodium Channel Inner Pore

    Science.gov (United States)

    Lipkind, Gregory M.

    2010-01-01

    The tricyclic anticonvulsant drugs phenytoin, carbamazepine, and lamotrigine block neuronal voltage-gated Na+ channels, and their binding sites to domain IV-S6 in the channel's inner pore overlap with those of local anesthetic drugs. These anticonvulsants are neutral, in contrast to the mostly positively charged local anesthetics, but their open/inactivated-state blocking affinities are similar. Using a model of the open pore of the Na+ channel that we developed by homology with the crystal structures of potassium channels, we have docked these three anticonvulsants with residues identified by mutagenesis as important for their binding energy. The three drugs show a common pharmacophore, including an aromatic ring that has an aromatic-aromatic interaction with Tyr-1771 of NaV1.2 and a polar amide or imide that interacts with the aromatic ring of Phe-1764 by a low-energy amino-aromatic hydrogen bond. The second aromatic ring is nearly at a right angle to the pharmacophore and fills the pore lumen, probably interacting with the other S6 segments and physically occluding the inner pore to block Na+ permeation. Hydrophobic interactions with this second aromatic ring may contribute an important component to binding for anticonvulsants, which compensates energetically for the absence of positive charge in their structures. Voltage dependence of block, their important therapeutic property, results from their interaction with Phe-1764, which connects them to the voltage sensors. Their use dependence is modest and this results from being neutral, with a fast drug off-rate after repolarization, allowing a normal action potential rate in the presence of the drugs. PMID:20643904

  7. Selective alteration of sodium channel gating by Australian funnel-web spider toxins.

    Science.gov (United States)

    Nicholson, G M; Little, M J; Tyler, M; Narahashi, T

    1996-01-01

    The actions of potent mammalian neurotoxins isolated from the venom of two Australian funnel-web spiders were investigated using both electrophysiological and neurochemical techniques. Whole-cell patch clamp recording of sodium currents in rat dorsal root ganglion neurons revealed that versutoxin (VTX), isolated from the venom of Hadronyche versuta, produced a concentration-dependent slowing or removal of tetrodotoxin-sensitive (TTX-S) sodium current inactivation and a reduction in peak TTX-S sodium current. In contrast, VTX had no effect on tetrodotoxin-resistant (TTX-R) sodium currents or potassium currents. VTX also shifted the voltage dependence of sodium channel activation in the hyperpolarizing direction and increased the rate of recovery from inactivation. Ion flux studies performed in rat brain synaptosomes also revealed that robustoxin (RTX), from the venom of Atrax robustus, and VTX both produced a partial activation of 22Na+ flux and an inhibition of batrachotoxin-activated 22Na+ flux. This inhibition of flux through batrachotoxin-activated channels was not due to an interaction with neurotoxin receptor site 1 since [3H]saxitoxin binding was unaffected. In addition, the partial activation of 22Na+ flux was not enhanced in the presence of alpha-scorpion toxin and further experiments suggest that VTX also enhances [3H]batrachotoxin binding. These selective actions of funnel-web spider toxins on sodium channel function are comparable to those of alpha-scorpion and sea anemone toxins which bind to neurotoxin receptor site 3 on the channel to slow channel inactivation profoundly. Also, these modifications of sodium channel gating and kinetics are consistent with actions of the spider toxins to produce repetitive firing of action potentials.

  8. Boolean gates on actin filaments

    Science.gov (United States)

    Siccardi, Stefano; Tuszynski, Jack A.; Adamatzky, Andrew

    2016-01-01

    Actin is a globular protein which forms long polar filaments in the eukaryotic cytoskeleton. Actin networks play a key role in cell mechanics and cell motility. They have also been implicated in information transmission and processing, memory and learning in neuronal cells. The actin filaments have been shown to support propagation of voltage pulses. Here we apply a coupled nonlinear transmission line model of actin filaments to study interactions between voltage pulses. To represent digital information we assign a logical TRUTH value to the presence of a voltage pulse in a given location of the actin filament, and FALSE to the pulse's absence, so that information flows along the filament with pulse transmission. When two pulses, representing Boolean values of input variables, interact, then they can facilitate or inhibit further propagation of each other. We explore this phenomenon to construct Boolean logical gates and a one-bit half-adder with interacting voltage pulses. We discuss implications of these findings on cellular process and technological applications.

  9. Butanol isomers exert distinct effects on voltage-gated calcium channel currents and thus catecholamine secretion in adrenal chromaffin cells.

    Directory of Open Access Journals (Sweden)

    Sarah McDavid

    Full Text Available Butanol (C4H10OH has been used both to dissect the molecular targets of alcohols/general anesthetics and to implicate phospholipase D (PLD signaling in a variety of cellular functions including neurotransmitter and hormone exocytosis. Like other primary alcohols, 1-butanol is a substrate for PLD and thereby disrupts formation of the intracellular signaling lipid phosphatidic acid. Because secondary and tertiary butanols do not undergo this transphosphatidylation, they have been used as controls for 1-butanol to implicate PLD signaling. Recently, selective pharmacological inhibitors of PLD have been developed and, in some cases, fail to block cellular functions previously ascribed to PLD using primary alcohols. For example, exocytosis of insulin and degranulation of mast cells are blocked by primary alcohols, but not by the PLD inhibitor FIPI. In this study we show that 1-butanol reduces catecholamine secretion from adrenal chromaffin cells to a much greater extent than tert-butanol, and that the PLD inhibitor VU0155056 has no effect. Using fluorescent imaging we show the effect of these drugs on depolarization-evoked calcium entry parallel those on secretion. Patch-clamp electrophysiology confirmed the peak amplitude of voltage-gated calcium channel currents (I(Ca is inhibited by 1-butanol, with little or no block by secondary or tert-butanol. Detailed comparison shows for the first time that the different butanol isomers exert distinct, and sometimes opposing, effects on the voltage-dependence and gating kinetics of I(Ca. We discuss these data with regard to PLD signaling in cellular physiology and the molecular targets of general anesthetics.

  10. Butanol isomers exert distinct effects on voltage-gated calcium channel currents and thus catecholamine secretion in adrenal chromaffin cells.

    Science.gov (United States)

    McDavid, Sarah; Bauer, Mary Beth; Brindley, Rebecca L; Jewell, Mark L; Currie, Kevin P M

    2014-01-01

    Butanol (C4H10OH) has been used both to dissect the molecular targets of alcohols/general anesthetics and to implicate phospholipase D (PLD) signaling in a variety of cellular functions including neurotransmitter and hormone exocytosis. Like other primary alcohols, 1-butanol is a substrate for PLD and thereby disrupts formation of the intracellular signaling lipid phosphatidic acid. Because secondary and tertiary butanols do not undergo this transphosphatidylation, they have been used as controls for 1-butanol to implicate PLD signaling. Recently, selective pharmacological inhibitors of PLD have been developed and, in some cases, fail to block cellular functions previously ascribed to PLD using primary alcohols. For example, exocytosis of insulin and degranulation of mast cells are blocked by primary alcohols, but not by the PLD inhibitor FIPI. In this study we show that 1-butanol reduces catecholamine secretion from adrenal chromaffin cells to a much greater extent than tert-butanol, and that the PLD inhibitor VU0155056 has no effect. Using fluorescent imaging we show the effect of these drugs on depolarization-evoked calcium entry parallel those on secretion. Patch-clamp electrophysiology confirmed the peak amplitude of voltage-gated calcium channel currents (I(Ca)) is inhibited by 1-butanol, with little or no block by secondary or tert-butanol. Detailed comparison shows for the first time that the different butanol isomers exert distinct, and sometimes opposing, effects on the voltage-dependence and gating kinetics of I(Ca). We discuss these data with regard to PLD signaling in cellular physiology and the molecular targets of general anesthetics.

  11. Sensory gating deficits in parents of schizophrenics

    Energy Technology Data Exchange (ETDEWEB)

    Waldo, M.; Madison, A.; Freedman, R. [Univ. of Colorado Health Sciences Center, Denver, CO (United States)] [and others

    1995-12-18

    Although schizophrenia clusters in families, it is not inherited in Mendelian fashion. This suggests that there may be alternative phenotypic expressions of genes that convey risk for schizophrenia, such as more elementary physiological or biochemical defects. One proposed phenotype is impaired inhibitory gating of the auditory evoked potential to repeated stimuli. Normally, the amplitude of the P50 response to the second stimulus is significantly less than the response to the first, but this gating of response is generally impaired in schizophrenia. Clinically unaffected individuals within a pedigree who have both an ancestral and descendant history of schizophrenia may be useful for studying whether this physiological defect is a possible alternative phenotype. We have studied inhibitory gating of the auditory P50 response to pairs of auditory stimuli in 17 nuclear families. In 11, there was one parent who had another relative with a chronic psychotic illness, in addition to the schizophrenic proband. AR of the parents with family histories of schizophrenia had gating of the P50 response similar to their schizophrenia offspring, whereas only 7% of the parents without family history had gating of the P50 response in the abnormal range. These results support loss of gating of the auditory P50 wave as an inherited deficit related to schizophrenia and suggest that studies of parents may help elucidate the neurobiological expression of genes that convey risk for schizophrenia. 36 refs., 2 figs., 2 tabs.

  12. VKCDB: Voltage-gated potassium channel database

    Directory of Open Access Journals (Sweden)

    Gallin Warren J

    2004-01-01

    Full Text Available Abstract Background The family of voltage-gated potassium channels comprises a functionally diverse group of membrane proteins. They help maintain and regulate the potassium ion-based component of the membrane potential and are thus central to many critical physiological processes. VKCDB (Voltage-gated potassium [K] Channel DataBase is a database of structural and functional data on these channels. It is designed as a resource for research on the molecular basis of voltage-gated potassium channel function. Description Voltage-gated potassium channel sequences were identified by using BLASTP to search GENBANK and SWISSPROT. Annotations for all voltage-gated potassium channels were selectively parsed and integrated into VKCDB. Electrophysiological and pharmacological data for the channels were collected from published journal articles. Transmembrane domain predictions by TMHMM and PHD are included for each VKCDB entry. Multiple sequence alignments of conserved domains of channels of the four Kv families and the KCNQ family are also included. Currently VKCDB contains 346 channel entries. It can be browsed and searched using a set of functionally relevant categories. Protein sequences can also be searched using a local BLAST engine. Conclusions VKCDB is a resource for comparative studies of voltage-gated potassium channels. The methods used to construct VKCDB are general; they can be used to create specialized databases for other protein families. VKCDB is accessible at http://vkcdb.biology.ualberta.ca.

  13. High-Confidence Quantum Gate Tomography

    Science.gov (United States)

    Johnson, Blake; da Silva, Marcus; Ryan, Colm; Kimmel, Shelby; Donovan, Brian; Ohki, Thomas

    2014-03-01

    Debugging and verification of high-fidelity quantum gates requires the development of new tools and protocols to unwrap the performance of the gate from the rest of the sequence. Randomized benchmarking tomography[2] allows one to extract full information of the unital portion of the gate with high confidence. We report experimental confirmation of the technique's applicability to quantum gate tomography. We show that the method is robust to common experimental imperfections such as imperfect single-shot readout and state preparation. We also demonstrate the ability to characterize non-Clifford gates. To assist in the experimental implementation we introduce two techniques. ``Atomic Cliffords'' use phase ramping and frame tracking to allow single-pulse implementation of the full group of single-qubit Clifford gates. Domain specific pulse sequencers allow rapid implementation of the many thousands of sequences needed. This research was funded by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), through the Army Research Office contract no. W911NF-10-1-0324.

  14. Radiation-Insensitive Inverse Majority Gates

    Science.gov (United States)

    Manohara, Harish; Mojarradi, Mohammad

    2008-01-01

    To help satisfy a need for high-density logic circuits insensitive to radiation, it has been proposed to realize inverse majority gates as microscopic vacuum electronic devices. In comparison with solid-state electronic devices ordinarily used in logic circuits, vacuum electronic devices are inherently much less adversely affected by radiation and extreme temperatures. The proposed development would involve state-of-the-art micromachining and recent advances in the fabrication of carbon-nanotube-based field emitters. A representative three-input inverse majority gate would be a monolithic, integrated structure that would include three gate electrodes, six bundles of carbon nanotubes (serving as electron emitters) at suitable positions between the gate electrodes, and an overhanging anode. The bundles of carbon nanotubes would be grown on degenerately doped silicon substrates that would be parts of the monolithic structure. The gate electrodes would be fabricated as parts of the monolithic structure by means of a double-silicon-on-insulator process developed at NASA's Jet Propulsion Laboratory. The tops of the bundles of carbon nanotubes would lie below the plane of the tops of the gate electrodes. The particular choice of shapes, dimensions, and relative positions of the electrodes and bundles of carbon nanotubes would provide for both field emission of electrons from the bundles of carbon nanotubes and control of the electron current to obtain the inverse majority function, which is described in the paper.

  15. Fetal Electrocardiogram (fECG Gated MRI

    Directory of Open Access Journals (Sweden)

    Martyn N.J. Paley

    2013-08-01

    Full Text Available We have developed a Magnetic Resonance Imaging (MRI-compatible system to enable gating of a scanner to the heartbeat of a foetus for cardiac, umbilical cord flow and other possible imaging applications. We performed radiofrequency safety testing prior to a fetal electrocardiogram (fECG gated imaging study in pregnant volunteers (n = 3. A compact monitoring device with advanced software capable of reliably detecting both the maternal electrocardiogram (mECG and fECG simultaneously was modified by the manufacturer (Monica Healthcare, Nottingham, UK to provide an external TTL trigger signal from the detected fECG which could be used to trigger a standard 1.5 T MR (GE Healthcare, Milwaukee, WI, USA gating system with suitable attenuation. The MR scanner was tested by triggering rapidly during image acquisition at a typical fetal heart rate (123 beats per minute using a simulated fECG waveform fed into the gating system. Gated MR images were also acquired from volunteers who were attending for a repeat fetal Central Nervous System (CNS examination using an additional rapid cardiac imaging sequence triggered from the measured fECG. No adverse safety effects were encountered. This is the first time fECG gating has been used with MRI and opens up a range of new possibilities to study a developing foetus.

  16. Strongly Coupled Cosmologies

    CERN Document Server

    Bonometto, S A; Musco, I; Mainini, R; Maccio', A V

    2014-01-01

    Models including an energy transfer from CDM to DE are widely considered in the literature, namely to allow DE a significant high-z density. Strongly Coupled cosmologies assume a much larger coupling between DE and CDM, together with the presence of an uncoupled warm DM component, as the role of CDM is mostly restricted to radiative eras. This allows us to preserve small scale fluctuations even if the warm particle, possibly a sterile neutrino, is quite light, O(100 eV). Linear theory and numerical simulations show that these cosmologies agree with LCDM on supergalactic scales; e.g., CMB spectra are substantially identical. Simultaneously, simulations show that they significantly ease problems related to the properties of MW satellites and cores in dwarfs. SC cosmologies also open new perspectives on early black hole formation, and possibly lead towards unificating DE and inflationary scalar fields.

  17. On Strong Cosmic Censorship

    CERN Document Server

    Isenberg, James

    2015-01-01

    For almost half of the one hundred year history of Einstein's theory of general relativity, Strong Cosmic Censorship has been one of its most intriguing conjectures. The SCC conjecture addresses the issue of the nature of the singularities found in most solutions of Einstein's gravitational field equations: Are such singularities generically characterized by unbounded curvature? Is the existence of a Cauchy horizon (and the accompanying extensions into spacetime regions in which determinism fails) an unstable feature of solutions of Einstein's equations? In this short review article, after briefly commenting on the history of the SCC conjecture, we survey some of the progress made in research directed either toward supporting SCC or toward uncovering some of its weaknesses. We focus in particular on model versions of SCC which have been proven for restricted families of spacetimes (e.g., the Gowdy spacetimes), and the role played by the generic presence of Asymptotically Velocity Term Dominated behavior in th...

  18. LIGO: The strong belief

    CERN Multimedia

    Antonella Del Rosso

    2016-01-01

    Twenty years of designing, building and testing a number of innovative technologies, with the strong belief that the endeavour would lead to a historic breakthrough. The Bulletin publishes an abstract of the Courier’s interview with Barry Barish, one of the founding fathers of LIGO.   The plots show the signals of gravitational waves detected by the twin LIGO observatories at Livingston, Louisiana, and Hanford, Washington. (Image: Caltech/MIT/LIGO Lab) On 11 February, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo collaborations published a historic paper in which they showed a gravitational signal emitted by the merger of two black holes. These results come after 20 years of hard work by a large collaboration of scientists operating the two LIGO observatories in the US. Barry Barish, Linde Professor of Physics, Emeritus at the California Institute of Technology and former Director of the Global Design Effort for the Internat...

  19. Finding Strong Bridges and Strong Articulation Points in Linear Time

    Science.gov (United States)

    Italiano, Giuseppe F.; Laura, Luigi; Santaroni, Federico

    Given a directed graph G, an edge is a strong bridge if its removal increases the number of strongly connected components of G. Similarly, we say that a vertex is a strong articulation point if its removal increases the number of strongly connected components of G. In this paper, we present linear-time algorithms for computing all the strong bridges and all the strong articulation points of directed graphs, solving an open problem posed in [2].

  20. Getting more out of biomedical documents with GATE's full lifecycle open source text analytics.

    Science.gov (United States)

    Cunningham, Hamish; Tablan, Valentin; Roberts, Angus; Bontcheva, Kalina

    2013-01-01

    This software article describes the GATE family of open source text analysis tools and processes. GATE is one of the most widely used systems of its type with yearly download rates of tens of thousands and many active users in both academic and industrial contexts. In this paper we report three examples of GATE-based systems operating in the life sciences and in medicine. First, in genome-wide association studies which have contributed to discovery of a head and neck cancer mutation association. Second, medical records analysis which has significantly increased the statistical power of treatment/outcome models in the UK's largest psychiatric patient cohort. Third, richer constructs in drug-related searching. We also explore the ways in which the GATE family supports the various stages of the lifecycle present in our examples. We conclude that the deployment of text mining for document abstraction or rich search and navigation is best thought of as a process, and that with the right computational tools and data collection strategies this process can be made defined and repeatable. The GATE research programme is now 20 years old and has grown from its roots as a specialist development tool for text processing to become a rather comprehensive ecosystem, bringing together software developers, language engineers and research staff from diverse fields. GATE now has a strong claim to cover a uniquely wide range of the lifecycle of text analysis systems. It forms a focal point for the integration and reuse of advances that have been made by many people (the majority outside of the authors' own group) who work in text processing for biomedicine and other areas. GATE is available online under GNU open source licences and runs on all major operating systems. Support is available from an active user and developer community and also on a commercial basis.

  1. Getting more out of biomedical documents with GATE's full lifecycle open source text analytics.

    Directory of Open Access Journals (Sweden)

    Hamish Cunningham

    Full Text Available This software article describes the GATE family of open source text analysis tools and processes. GATE is one of the most widely used systems of its type with yearly download rates of tens of thousands and many active users in both academic and industrial contexts. In this paper we report three examples of GATE-based systems operating in the life sciences and in medicine. First, in genome-wide association studies which have contributed to discovery of a head and neck cancer mutation association. Second, medical records analysis which has significantly increased the statistical power of treatment/outcome models in the UK's largest psychiatric patient cohort. Third, richer constructs in drug-related searching. We also explore the ways in which the GATE family supports the various stages of the lifecycle present in our examples. We conclude that the deployment of text mining for document abstraction or rich search and navigation is best thought of as a process, and that with the right computational tools and data collection strategies this process can be made defined and repeatable. The GATE research programme is now 20 years old and has grown from its roots as a specialist development tool for text processing to become a rather comprehensive ecosystem, bringing together software developers, language engineers and research staff from diverse fields. GATE now has a strong claim to cover a uniquely wide range of the lifecycle of text analysis systems. It forms a focal point for the integration and reuse of advances that have been made by many people (the majority outside of the authors' own group who work in text processing for biomedicine and other areas. GATE is available online under GNU open source licences and runs on all major operating systems. Support is available from an active user and developer community and also on a commercial basis.

  2. An update on transcriptional and post-translational regulation of brain voltage-gated sodium channels.

    Science.gov (United States)

    Onwuli, Donatus O; Beltran-Alvarez, Pedro

    2016-03-01

    Voltage-gated sodium channels are essential proteins in brain physiology, as they generate the sodium currents that initiate neuronal action potentials. Voltage-gated sodium channels expression, localisation and function are regulated by a range of transcriptional and post-translational mechanisms. Here, we review our understanding of regulation of brain voltage-gated sodium channels, in particular SCN1A (NaV1.1), SCN2A (NaV1.2), SCN3A (NaV1.3) and SCN8A (NaV1.6), by transcription factors, by alternative splicing, and by post-translational modifications. Our focus is strongly centred on recent research lines, and newly generated knowledge.

  3. Voltage-dependent amplification of synaptic inputs in respiratory motoneurones

    DEFF Research Database (Denmark)

    Enríquez Denton, M; Wienecke, Jacob; Zhang, Mengliang

    2012-01-01

    of the inputs. Knowledge of these processes is important in understanding conditions such as motoneurone disease, or the spasticity that can follow spinal cord injury or stroke Respiration is a natural motor act that continues normally under experimental conditions, and this study investigated, for the first...

  4. Voltage-Dependent Intrinsic Bursting in Olfactory Bulb Golgi Cells

    Science.gov (United States)

    Pressler, R. Todd; Rozman, Peter A.; Strowbridge, Ben W.

    2013-01-01

    In the mammalian olfactory bulb (OB), local synaptic circuits modulate the evolving pattern of activity in mitral and tufted cells following olfactory sensory stimulation. GABAergic granule cells, the most numerous interneuron subtype in this brain region, have been extensively studied. However, classic studies using Golgi staining methods…

  5. Voltage-Dependent Intrinsic Bursting in Olfactory Bulb Golgi Cells

    Science.gov (United States)

    Pressler, R. Todd; Rozman, Peter A.; Strowbridge, Ben W.

    2013-01-01

    In the mammalian olfactory bulb (OB), local synaptic circuits modulate the evolving pattern of activity in mitral and tufted cells following olfactory sensory stimulation. GABAergic granule cells, the most numerous interneuron subtype in this brain region, have been extensively studied. However, classic studies using Golgi staining methods…

  6. Gated SIT Vidicon Streak Tube

    Science.gov (United States)

    Dunbar, D. L.; Yates, G. J.; Black, J. P.

    1986-01-01

    A recently developed prototype streak tube designed to produce high gain and resolution by incorporating the streak and readout functions in one envelope thereby minimizing photon-to-charge transformations and eliminating external coupling losses is presented. The tube is based upon a grid-gated Silicon-Intensified-Target Vidicon (SITV) with integral Focus Projection Scan (FPS) TV readout. Demagnifying electron optics (m=0.63) in the image section map the 40-mm-diameter photocathode image unto a 25-mm-diameter silicon target where gains >= 103 are achieved with only 10 KV accelerating voltage. This is compared with much lower gains (~ 50) at much higher voltages (~ 30 KV) reported for streak tubes using phosphor screens. Because SIT technology is well established means for electron imaging in vacuum, such fundamental problems as "backside thinning" required for electron imaging unto CCDs do not exist. The high spatial resolution (~ 30 1p/mm), variable scan formats, and high speed electrostatic deflection (250 mm2 areas are routinely rastered with 256 scan lines in 1.6 ms) available from FPS readout add versatility not available in CCD devices. Theoretical gain and spatial resolution for this design (developed jointly by Los Alamos National Laboratory and General Electric Co.) are compared with similar calculations and measured data obtained for RCA 73435 streaks fiber optically coupled to (1) 25-mm-diameter SIT FPS vidicons and (2) 40-mm-diameter MCPTs (proximity-focused microchannel plate image intensifier tubes) fiber optically coupled to 18-mm-diameter Sb2S3 FPS vidicons. Sweep sensitivity, shutter ratio, and record lengths for nanosecond duration (20 to 200 ns) streak applications are discussed.

  7. John Strong (1941 - 2006)

    CERN Multimedia

    Wickens, F

    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on Monday 31st July, a few days before his 65th birthday John started his career working with a group from Westfield College, under the leadership of Ted Bellamy. He obtained his PhD and spent the early part of his career on experiments at Rutherford Appleton Laboratory (RAL), but after the early 1970s his research was focussed on experiments in CERN. Over the years he made a number of notable contributions to experiments in CERN: The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras to record the sparks in the spark chambers; He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems; He was responsible for the second level trigger system for the ALEPH detector and spent five years leading a team that designed and built the system, which ran for twelve years with only minor interventions. Following ALEPH he tur...

  8. Foreshocks of strong earthquakes

    Science.gov (United States)

    Guglielmi, A. V.; Sobisevich, L. E.; Sobisevich, A. L.; Lavrov, I. P.

    2014-07-01

    The specific enhancement of ultra-low-frequency (ULF) electromagnetic oscillations a few hours prior to the strong earthquakes, which was previously mentioned in the literature, motivated us to search for the distinctive features of the mechanical (foreshock) activity of the Earth's crust in the epicentral zones of the future earthquakes. Activation of the foreshocks three hours before the main shock is revealed, which is roughly similar to the enhancement of the specific electromagnetic ULF emission. It is hypothesized that the round-the-world seismic echo signals from the earthquakes, which form the peak of energy release 2 h 50 min before the main events, act as the triggers of the main shocks due to the cumulative action of the surface waves converging to the epicenter. It is established that the frequency of the fluctuations in the foreshock activity decreases at the final stages of the preparation of the main shocks, which probably testifies to the so-called mode softening at the approach of the failure point according to the catastrophe theory.

  9. Controlled Logic Gates-Switch Gate and Fredkin Gate Based on Enzyme-Biocatalyzed Reactions Realized in Flow Cells.

    Science.gov (United States)

    Fratto, Brian E; Katz, Evgeny

    2016-04-04

    Controlled logic gates, where the logic operations on the Data inputs are performed in the way determined by the Control signal, were designed in a chemical fashion. Specifically, the systems where the Data output signals directed to various output channels depending on the logic value of the Control input signal have been designed based on enzyme biocatalyzed reactions performed in a multi-cell flow system. In the Switch gate one Data signal was directed to one of two possible output channels depending on the logic value of the Control input signal. In the reversible Fredkin gate the routing of two Data signals between two output channels is controlled by the third Control signal. The flow devices were created using a network of flow cells, each modified with one enzyme that biocatalyzed one chemical reaction. The enzymatic cascade was realized by moving the solution from one reacting cell to another which were organized in a specific network. The modular design of the enzyme-based systems realized in the flow device allowed easy reconfiguration of the logic system, thus allowing simple extension of the logic operation from the 2-input/3-output channels in the Switch gate to the 3-input/3-output channels in the Fredkin gate. Further increase of the system complexity for realization of various logic processes is feasible with the use of the flow cell modular design. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Enhancing a slow and weak optomechanical nonlinearity with delayed quantum feedback to implement a CPHASE gate

    CERN Document Server

    Wang, Zhaoyou

    2016-01-01

    We show that the effective optical nonlinearity of a cavity optomechanical system can be used to implement quantum gates between propagating photons. By using quantum feedback, we can enhance a slow and small optical nonlinearity to generate a large nonlinear phase shift between two spatially separated temporal modes of a propagating electromagnetic field. This allows us to implement a CPHASE gate between the two modes. After presenting a semiclassical derivation of the operation of the gate, we verify the result by a full simulation of the state of the quantum field in the waveguide coupled to a cavity. To efficiently solve the Schr\\"odinger equation of the full system, we develop a matrix product state approach that keeps track of the entangled full quantum state of the coupled system. These simulations verify the operation of the gate in the weak coupling regime where the semiclassical approximation is valid. In addition, we observe a major reduction in gate fidelity as we approach the vacuum strong coupli...

  11. Memory effect in silicon time-gated single-photon avalanche diodes

    Energy Technology Data Exchange (ETDEWEB)

    Dalla Mora, A.; Contini, D., E-mail: davide.contini@polimi.it; Di Sieno, L. [Dipartimento di Fisica, Politecnico di Milano, Piazza Leonardo da Vinci 32, I-20133 Milano (Italy); Tosi, A.; Boso, G.; Villa, F. [Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Piazza Leonardo da Vinci 32, I-20133 Milano (Italy); Pifferi, A. [Dipartimento di Fisica, Politecnico di Milano, Piazza Leonardo da Vinci 32, I-20133 Milano (Italy); CNR, Istituto di Fotonica e Nanotecnologie, Piazza Leonardo da Vinci 32, I-20133 Milano (Italy)

    2015-03-21

    We present a comprehensive characterization of the memory effect arising in thin-junction silicon Single-Photon Avalanche Diodes (SPADs) when exposed to strong illumination. This partially unknown afterpulsing-like noise represents the main limiting factor when time-gated acquisitions are exploited to increase the measurement dynamic range of very fast (picosecond scale) and faint (single-photon) optical signals following a strong stray one. We report the dependences of this unwelcome signal-related noise on photon wavelength, detector temperature, and biasing conditions. Our results suggest that this so-called “memory effect” is generated in the deep regions of the detector, well below the depleted region, and its contribution on detector response is visible only when time-gated SPADs are exploited to reject a strong burst of photons.

  12. Statistical determinations of the gating windows in the respiratory gated radiotherapy using the visible guiding system

    CERN Document Server

    Oh, Se An; Lee, Hyun Jeong; Kim, Sung Kyu

    2015-01-01

    Purpose: Respiratory gated radiation therapy (RGRT) is used to minimize the radiation dose to normal tissue in lung cancer patients. Determinations of the gating window in the respiratory phase of patients are important in RGRT but it is not easy. The objective of this study was to determine the optimal gating window with a visible guiding system in RGRT. Materials and Methods: Between April and October in 2014 the breathing signals of 23 lung cancer patients were recorded with a Real-time Position Management (RPM) respiratory gating system (Varian, USA). We performed statistical analysis with breathing signals to find the optimal gating window for the guided breathing for RGRT. Results: 19 of the 23 patients showed statistically significant differences (p < 0.05) when the breathing signals obtained before and after breathing training were compared, The standard deviation of the respiration signals after breathing training was the lowest in the phase of 30 % - 70 % (p < 0.05). Conclusions: RGRT with RPM...

  13. Contribution of the S5-pore-S6 domain to the gating characteristics of the cation channels TRPM2 and TRPM8.

    Science.gov (United States)

    Kühn, Frank J P; Witschas, Katja; Kühn, Cornelia; Lückhoff, Andreas

    2010-08-27

    The closely related cation channels TRPM2 and TRPM8 show completely different requirements for stimulation and are regulated by Ca(2+) in an opposite manner. TRPM8 is basically gated in a voltage-dependent process enhanced by cold temperatures and cooling compounds such as menthol and icilin. The putative S4 voltage sensor of TRPM8 is closely similar to that of TRPM2, which, however, is mostly devoid of voltage sensitivity. To gain insight into principal interactions of critical channel domains during the gating process, we created chimeras in which the entire S5-pore-S6 domains were reciprocally exchanged. The chimera M2-M8P (i.e. TRPM2 with the pore of TRPM8) responded to ADP-ribose and hydrogen peroxide and was regulated by extracellular and intracellular Ca(2+) as was wild-type TRPM2. Single-channel recordings revealed the characteristic pattern of TRPM2 with extremely long open times. Only at far-negative membrane potentials (-120 to -140 mV) did differences become apparent because currents were reduced by hyperpolarization in M2-M8P but not in TRPM2. The reciprocal chimera, M8-M2P, showed currents after stimulation with high concentrations of menthol and icilin, but these currents were only slightly larger than in controls. The transfer of the NUDT9 domain to the C terminus of TRPM8 produced a channel sensitive to cold, menthol, or icilin but insensitive to ADP-ribose or hydrogen peroxide. We conclude that the gating processes in TRPM2 and TRPM8 differ in their requirements for specific structures within the pore. Moreover, the regulation by extracellular and intracellular Ca(2+) and the single-channel properties in TRPM2 are not determined by the S5-pore-S6 region.

  14. Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine.

    Science.gov (United States)

    Wang, Ying; Mi, Jianxun; Lu, Ka; Lu, Yanxin; Wang, KeWei

    2015-01-01

    Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that are considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias and relief of pain. To gain mechanistic insights into action of anti-arrhythmics, we characterized biophysical properties of Nav1.5 and Nav1.7 channels stably expressed in HEK293 cells and compared their use-dependent block in response to mexiletine and lidocaine using whole-cell patch clamp recordings. While the voltage-dependent activation of Nav1.5 or Nav1.7 was not affected by mexiletine and lidocaine, the steady-state fast and slow inactivation of Nav1.5 and Nav1.7 were significantly shifted to hyperpolarized direction by either mexiletine or lidocaine in dose-dependent manner. Both mexiletine and lidocaine enhanced the slow component of closed-state inactivation, with mexiletine exerting stronger inhibition on either Nav1.5 or Nav1.7. The recovery from inactivation of Nav1.5 or Nav1.7 was significantly prolonged by mexiletine compared to lidocaine. Furthermore, mexiletine displayed a pronounced and prominent use-dependent inhibition of Nav1.5 than lidocaine, but not Nav1.7 channels. Taken together, our findings demonstrate differential responses to blockade by mexiletine and lidocaine that preferentially affect the gating of Nav1.5, as compared to Nav1.7; and mexiletine exhibits stronger use-dependent block of Nav1.5. The differential gating properties of Nav1.5 and Nav1.7 in response to mexiletine and lidocaine may help explain the drug effectiveness and advance in new designs of safe and specific sodium channel blockers for treatment of cardiac arrhythmia or pain.

  15. Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that are considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias and relief of pain. To gain mechanistic insights into action of anti-arrhythmics, we characterized biophysical properties of Nav1.5 and Nav1.7 channels stably expressed in HEK293 cells and compared their use-dependent block in response to mexiletine and lidocaine using whole-cell patch clamp recordings. While the voltage-dependent activation of Nav1.5 or Nav1.7 was not affected by mexiletine and lidocaine, the steady-state fast and slow inactivation of Nav1.5 and Nav1.7 were significantly shifted to hyperpolarized direction by either mexiletine or lidocaine in dose-dependent manner. Both mexiletine and lidocaine enhanced the slow component of closed-state inactivation, with mexiletine exerting stronger inhibition on either Nav1.5 or Nav1.7. The recovery from inactivation of Nav1.5 or Nav1.7 was significantly prolonged by mexiletine compared to lidocaine. Furthermore, mexiletine displayed a pronounced and prominent use-dependent inhibition of Nav1.5 than lidocaine, but not Nav1.7 channels. Taken together, our findings demonstrate differential responses to blockade by mexiletine and lidocaine that preferentially affect the gating of Nav1.5, as compared to Nav1.7; and mexiletine exhibits stronger use-dependent block of Nav1.5. The differential gating properties of Nav1.5 and Nav1.7 in response to mexiletine and lidocaine may help explain the drug effectiveness and advance in new designs of safe and specific sodium channel blockers for treatment of cardiac arrhythmia or pain.

  16. Fluorescence rejection in resonance Raman spectroscopy using a picosecond-gated intensified charge-coupled device camera.

    Science.gov (United States)

    Efremov, Evtim V; Buijs, Joost B; Gooijer, Cees; Ariese, Freek

    2007-06-01

    A Raman instrument was assembled and tested that rejects typically 98-99% of background fluorescence. Use is made of short (picosecond) laser pulses and time-gated detection in order to record the Raman signals during the pulse while blocking most of the fluorescence. Our approach uses an ultrafast-gated intensified charge-coupled device (ICCD) camera as a simple and straightforward alternative to ps Kerr gating. The fluorescence rejection efficiency depends mainly on the fluorescence lifetime and on the closing speed of the gate (which is about 80 ps in our setup). A formula to calculate this rejection factor is presented. The gated intensifier can be operated at 80 MHz, so high repetition rates and low pulse energies can be used, thus minimizing photodegradation. For excitation we use a frequency-tripled or -doubled Ti : sapphire laser with a pulse width of 3 ps; it should not be shorter in view of the required spectral resolution. Other critical aspects tested include intensifier efficiency as a function of gate width, uniformity of the gate pulse across the spectrum, and spectral resolution in comparison with ungated detection. The total instrumental resolution is 7 cm(-1) in the blue and 15 cm(-1) in the ultraviolet (UV) region. The setup allows one to use resonance Raman spectroscopy (RRS) for extra sensitivity and selectivity, even in the case of strong background fluorescence. Excitation wavelengths in the visible or UV range no longer have to be avoided. The effectiveness of this setup is demonstrated on a test system: pyrene in the presence of toluene fluorescence (lambda(exc) = 257 nm). Furthermore, good time-gated RRS spectra are shown for a strongly fluorescent flavoprotein (lambda(exc) = 405 nm). Advantages and disadvantages of this approach for RRS are discussed.

  17. Iron Gates Natural Park - Administration and Management

    Directory of Open Access Journals (Sweden)

    Sînziana Pauliuc

    2016-11-01

    Full Text Available This paper analyzes the management and administration of one of the largest, beautiful and complex natural parks from Romania, the Iron Gates Natural Park. The management plan is a frame of integration of the biodiversity conservation problems and protection of the natural and cultural environment that also supports socio-economic development of Iron Gates Natural Park. It is also an instrument of dialog between the institutions which coordinate this area. The management plan is a document approved by H.G 1048/2013 and it resulted after consulting the interested factors of the area (city halls, local and central authorities, civil society. The administration of Iron Gates Natural Park has a new structure, founded in 2003 and is working as a subunit of Forest-National Administration (Romsilva, which assures the necessary personal and equipment for administrating the area. The area has the status of: Natural Park, Natura 2000 and Ramsar site. The forest represents 65% of the total area, 98% being a state property. Analysing Iron Gates Natural Park documents (Iron Gates Natural Park management plan, scientific council and park administration documents, visits and observations within park, we can conclude that the park has a good administration leaded by the scientific councils, who also achieved many successful European projects.

  18. Szilard engine reversibility as quantum gate function

    Science.gov (United States)

    Mihelic, F. Matthew

    2012-06-01

    A quantum gate is a logically and thermodynamically reversible situation that effects a unitary transformation of qubits of superimposed information, and essentially constitutes a situation for a reversible quantum decision. A quantum decision is a symmetry break, and the effect of the function of a Szilard engine is a symmetry break. A quantum gate is a situation in which a reversible quantum decision can be made, and so if a logically and thermodynamically reversible Szilard engine can be theoretically constructed then it would function as a quantum gate. While the traditionally theorized Szilard engine is not thermodynamically reversible, if one of the bounding walls of a Szilard engine were to be constructed out of the physical information by which it functions in such a manner as to make that information available to both sides of the wall simultaneously, then such a Szilard engine would be both logically and thermodynamically reversible, and thus capable of function as a quantum gate. A theoretical model of the special case of a reversible Szilard engine functioning as a quantum gate is presented and discussed, and since a quantum decision is made when the shutter of a Szilard engine closes, the coherence of linked reversible Szilard engines should be considered as a state during which all of the shutters of linked Szilard engines are open simultaneously.

  19. Variable Block Carry Skip Logic using Reversible Gates

    OpenAIRE

    Islam, Md. Rafiqul; Islam, Md. Saiful; Karim, Muhammad Rezaul; Mahmud, Abdullah Al; Babu, Hafiz Md. Hasan

    2010-01-01

    Reversible circuits have applications in digital signal processing, computer graphics, quantum computation and cryptography. In this paper, a generalized k*k reversible gate family is proposed and a 3*3 gate of the family is discussed. Inverter, AND, OR, NAND, NOR, and EXOR gates can be realized by this gate. Implementation of a full-adder circuit using two such 3*3 gates is given. This full-adder circuit contains only two reversible gates and produces no extra garbage outputs. The proposed f...

  20. Multibit CkNOT quantum gates via Rydberg blockade

    DEFF Research Database (Denmark)

    Isenhower, L.; Saffman, Mark; Mølmer, Klaus

    2011-01-01

    Long range Rydberg blockade interactions have the potential for efficient implementation of quantum gates between multiple atoms. Here we present and analyze a protocol for implementation of a k-atom controlled NOT (CkNOT) neutral atom gate. This gate can be implemented using sequential or simult......Long range Rydberg blockade interactions have the potential for efficient implementation of quantum gates between multiple atoms. Here we present and analyze a protocol for implementation of a k-atom controlled NOT (CkNOT) neutral atom gate. This gate can be implemented using sequential...

  1. A gate size estimation algorithm for data association filters

    Institute of Scientific and Technical Information of China (English)

    WANG MingHui; WAN Qun; YOU ZhiSheng

    2008-01-01

    The problem of forming validation regions or gates for new sensor measurements obtained when tracking targets in clutter is considered. Since the gate size is an integral part of the data association filter, this paper is intended to describe a way of estimating the gate size via the performance of the data association filter. That is, the gate size can be estimated by looking for the optimal performance of the data association filter. Simulations show that this estimation method of the gate size offers advantages over the common and classical estimation methods of the gate size, especially in a heavy clutter and/or false alarm environment.

  2. AN IMPROVED DESIGN OF A MULTIPLIER USING REVERSIBLE LOGIC GATES

    Directory of Open Access Journals (Sweden)

    H.R.BHAGYALAKSHMI

    2010-08-01

    Full Text Available Reversible logic gates are very much in demand for the future computing technologies as they are known to produce zero power dissipation under ideal conditions. This paper proposes an improved design of a multiplier using reversible logic gates. Multipliers are very essential for the construction of various computational units of a quantum computer. The quantum cost of a reversible logic circuit can be minimized by reducing the number of reversible logic gates. For this two 4*4 reversible logic gates called a DPG gate and a BVF gate are used.

  3. Fluorescence-tracking of activation gating in human ERG channels reveals rapid S4 movement and slow pore opening.

    Directory of Open Access Journals (Sweden)

    Zeineb Es-Salah-Lamoureux

    Full Text Available BACKGROUND: hERG channels are physiologically important ion channels which mediate cardiac repolarization as a result of their unusual gating properties. These are very slow activation compared with other mammalian voltage-gated potassium channels, and extremely rapid inactivation. The mechanism of slow activation is not well understood and is investigated here using fluorescence as a direct measure of S4 movement and pore opening. METHODS AND FINDINGS: Tetramethylrhodamine-5-maleimide (TMRM fluorescence at E519 has been used to track S4 voltage sensor movement, and channel opening and closing in hERG channels. Endogenous cysteines (C445 and C449 in the S1-S2 linker bound TMRM, which caused a 10 mV hyperpolarization of the V((1/2 of activation to -27.5+/-2.0 mV, and showed voltage-dependent fluorescence signals. Substitution of S1-S2 linker cysteines with valines allowed unobstructed recording of S3-S4 linker E519C and L520C emission signals. Depolarization of E519C channels caused rapid initial fluorescence quenching, fit with a double Boltzmann relationship, F-V(ON, with V((1/2 (,1 = -37.8+/-1.7 mV, and V((1/2 (,2 = 43.5+/-7.9 mV. The first phase, V((1/2 (,1, was approximately 20 mV negative to the conductance-voltage relationship measured from ionic tail currents (G-V((1/2 = -18.3+/-1.2 mV, and relatively unchanged in a non-inactivating E519C:S620T mutant (V((1/2 = -34.4+/-1.5 mV, suggesting the fast initial fluorescence quenching tracked S4 voltage sensor movement. The second phase of rapid quenching was absent in the S620T mutant. The E519C fluorescence upon repolarization (V((1/2 = -20.6+/-1.2, k = 11.4 mV and L520C quenching during depolarization (V((1/2 = -26.8+/-1.0, k = 13.3 mV matched the respective voltage dependencies of hERG ionic tails, and deactivation time constants from -40 to -110 mV, suggesting they detected pore-S4 rearrangements related to ionic current flow during pore opening and closing. CONCLUSION: THE DATA INDICATE: 1

  4. A quantum logic gate between a solid-state quantum bit and a photon

    CERN Document Server

    Kim, Hyochul; Shen, Thomas C; Solomon, Glenn S; Waks, Edo; 10.1038/nphoton.2013.48

    2013-01-01

    Integrated quantum photonics provides a promising route towards scalable solid-state implementations of quantum networks, quantum computers, and ultra-low power opto-electronic devices. A key component for many of these applications is the photonic quantum logic gate, where the quantum state of a solid-state quantum bit (qubit) conditionally controls the state of a photonic qubit. These gates are crucial for development of robust quantum networks, non-destructive quantum measurements, and strong photon-photon interactions. Here we experimentally realize a quantum logic gate between an optical photon and a solid-state qubit. The qubit is composed of a quantum dot (QD) strongly coupled to a nano-cavity, which acts as a coherently controllable qubit system that conditionally flips the polarization of a photon on picosecond timescales, implementing a controlled-NOT (cNOT) gate. Our results represent an important step towards solid-state quantum networks and provide a versatile approach for probing QD-photon inter...

  5. Realization of allowable qeneralized quantum gates

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The most general duality gates were introduced by Long,Liu and Wang and named allowable generalized quantum gates (AGQGs,for short).By definition,an allowable generalized quantum gate has the form of U=YfkjsckUK,where Uk’s are unitary operators on a Hilbert space H and the coefficients ck’s are complex numbers with |Yfijo ck\\ ∧ 1 an d 1ck| <1 for all k=0,1,...,d-1.In this paper,we prove that an AGQG U=YfkZo ck∧k is realizable,i.e.there are two d by d unitary matrices W and V such that ck=W0kVk0 (0

  6. Transversal Clifford gates on folded surface codes

    Science.gov (United States)

    Moussa, Jonathan E.

    2016-10-01

    Surface and color codes are two forms of topological quantum error correction in two spatial dimensions with complementary properties. Surface codes have lower-depth error detection circuits and well-developed decoders to interpret and correct errors, while color codes have transversal Clifford gates and better code efficiency in the number of physical qubits needed to achieve a given code distance. A formal equivalence exists between color codes and folded surface codes, but it does not guarantee the transferability of any of these favorable properties. However, the equivalence does imply the existence of constant-depth circuit implementations of logical Clifford gates on folded surface codes. We achieve and improve this result by constructing two families of folded surface codes with transversal Clifford gates. This construction is presented generally for qudits of any dimension. The specific application of these codes to universal quantum computation based on qubit fusion is also discussed.

  7. TOURISM IN THE TOURIST AREA "IRON GATES"

    Directory of Open Access Journals (Sweden)

    DINU LOREDANA

    2015-12-01

    Full Text Available This paper wants to highlight the trends of tourist demanding from the touristic area Iron Gates. We will see that the future of tourism include new forms such as those caused by the increased interest in areas with agritourism attractions or areas and portions of parks and nature reserves, which will raise the attractiveness of Danube, putting in a new pole of attraction area. Thus, we conducted a research based on survey among visitors on the tourist area "Iron Gates". The main endpoint based on survey was highlighting the motivation that determined the choice of the tourist area "Iron Gates", but also knowledge of consumer satisfaction for the tourists to the visited area (tourist product studied. The main objectives were, of course, linked with socio - economic and demographic characteristics of tourists to form a clearer picture of the motivational factors involved.

  8. Four-gate transistor analog multiplier circuit

    Science.gov (United States)

    Mojarradi, Mohammad M. (Inventor); Blalock, Benjamin (Inventor); Cristoloveanu, Sorin (Inventor); Chen, Suheng (Inventor); Akarvardar, Kerem (Inventor)

    2011-01-01

    A differential output analog multiplier circuit utilizing four G.sup.4-FETs, each source connected to a current source. The four G.sup.4-FETs may be grouped into two pairs of two G.sup.4-FETs each, where one pair has its drains connected to a load, and the other par has its drains connected to another load. The differential output voltage is taken at the two loads. In one embodiment, for each G.sup.4-FET, the first and second junction gates are each connected together, where a first input voltage is applied to the front gates of each pair, and a second input voltage is applied to the first junction gates of each pair. Other embodiments are described and claimed.

  9. TRANSISTOR IMPLEMENTATION OF REVERSIBLE PRT GATES

    Directory of Open Access Journals (Sweden)

    RASHMI S.B,

    2011-03-01

    Full Text Available Reversible logic has emerged as one of the most important approaches for power optimization with its application in low power VLSI design. Reversible or information lossless circuits have applications in nanotechnology, digital signal processing, communication, computer graphics and cryptography. They are also a fundamental requirement in the emerging field of quantum computing. In this paper, two newoptimized universal gates are proposed. One of them has an ability to operate as a reversible half adder and half subtractor imultaneously. Another one acts only as half adder with minimum transistor count. The reversible gates are evaluated in terms of number of transistor count, critical path, garbage outputs and one to one mapping. Here transistor implementation of the proposed gates is done by using Virtuoso tool of cadence. Based on the results of the analysis, some of the trade-offs are made in the design to improve the efficiency.

  10. Control of terahertz nonlinear transmission with electrically gated graphene metadevices

    Science.gov (United States)

    Choi, Hyun Joo; Baek, In Hyung; Kang, Bong Joo; Kim, Hyeon-Don; Oh, Sang Soon; Hamm, Joachim M.; Pusch, Andreas; Park, Jagang; Lee, Kanghee; Son, Jaehyeon; Jeong, Young U. K.; Hess, Ortwin; Rotermund, Fabian; Min, Bumki

    2017-02-01

    Graphene, which is a two-dimensional crystal of carbon atoms arranged in a hexagonal lattice, has attracted a great amount of attention due to its outstanding mechanical, thermal and electronic properties. Moreover, graphene shows an exceptionally strong tunable light-matter interaction that depends on the Fermi level - a function of chemical doping and external gate voltage - and the electromagnetic resonance provided by intentionally engineered structures. In the optical regime, the nonlinearities of graphene originated from the Pauli blocking have already been exploited for mode-locking device applications in ultrafast laser technology, whereas nonlinearities in the terahertz regime, which arise from a reduction in conductivity due to carrier heating, have only recently been confirmed experimentally. Here, we investigated two key factors for controlling nonlinear interactions of graphene with an intense terahertz field. The induced transparencies of graphene can be controlled effectively by engineering meta-atoms and/or changing the number of charge carriers through electrical gating. Additionally, nonlinear phase changes of the transmitted terahertz field can be observed by introducing the resonances of the meta-atoms.

  11. Control of terahertz nonlinear transmission with electrically gated graphene metadevices

    Science.gov (United States)

    Choi, Hyun Joo; Baek, In Hyung; Kang, Bong Joo; Kim, Hyeon-Don; Oh, Sang Soon; Hamm, Joachim M.; Pusch, Andreas; Park, Jagang; Lee, Kanghee; Son, Jaehyeon; Jeong, Young U. k.; Hess, Ortwin; Rotermund, Fabian; Min, Bumki

    2017-01-01

    Graphene, which is a two-dimensional crystal of carbon atoms arranged in a hexagonal lattice, has attracted a great amount of attention due to its outstanding mechanical, thermal and electronic properties. Moreover, graphene shows an exceptionally strong tunable light-matter interaction that depends on the Fermi level - a function of chemical doping and external gate voltage - and the electromagnetic resonance provided by intentionally engineered structures. In the optical regime, the nonlinearities of graphene originated from the Pauli blocking have already been exploited for mode-locking device applications in ultrafast laser technology, whereas nonlinearities in the terahertz regime, which arise from a reduction in conductivity due to carrier heating, have only recently been confirmed experimentally. Here, we investigated two key factors for controlling nonlinear interactions of graphene with an intense terahertz field. The induced transparencies of graphene can be controlled effectively by engineering meta-atoms and/or changing the number of charge carriers through electrical gating. Additionally, nonlinear phase changes of the transmitted terahertz field can be observed by introducing the resonances of the meta-atoms. PMID:28216677

  12. Operational life prediction on gating image intensifier

    Science.gov (United States)

    Dong, Yu-hui; Shen, Zhi-guo; Li, Zhong-li

    2009-07-01

    Operational life is one of the important parameters to evaluate second and super second generation image intensifiers. It can be used not only to monitor manufacturing technique in product line, then the technology on photocathode processing, MCP degassing and MCP producing can be adjusted promptly, but also to eliminate the image intensifiers which have hidden risk on operational life as early as possible. Recently gating image intensifiers are used widely, method to estimate the operational life of gating image intensifier related to its practical operate mode and working condition need to be established urgently. The least square method to analyze the operational life test data in product line was introduced in this paper. Now the data can be analyzed with convenient statistic analyze function on Excel. Using "worksheet function" and "chart wizard" and "data analysis" on Excel to do the least square method calculation, spreadsheets are established to do complex data calculation with worksheet functions. Based on them, formulas to monitor the technology parameters were derived, and the conclusion that the operational life was only related to the decrease slope of photocathode exponential fit curve was made. The decrease slope of photocathode sensitivity exponential fit curve and the decrease percent of the exponential fit photocathode sensitivity can be used to evaluate the qualification of the operational life rapidly. The mathematic models for operational life prediction on image intensifier and gating image intensifier are established respectively based on the acceptable values of the decrease percent of the exponential fit photocathode sensitivity and the expecting signal to noise ratio. The equations predicting the operational life related to duty cycle and input light level on gating image intensifier were derived, and the relationship between them were discussed too. The theory foundation were made herein, so the user can select proper gating image

  13. Cyclic groups and quantum logic gates

    Science.gov (United States)

    Pourkia, Arash; Batle, J.; Raymond Ooi, C. H.

    2016-10-01

    We present a formula for an infinite number of universal quantum logic gates, which are 4 by 4 unitary solutions to the Yang-Baxter (Y-B) equation. We obtain this family from a certain representation of the cyclic group of order n. We then show that this discrete family, parametrized by integers n, is in fact, a small sub-class of a larger continuous family, parametrized by real numbers θ, of universal quantum gates. We discuss the corresponding Yang-Baxterization and related symmetries in the concomitant Hamiltonian.

  14. Coherent spaces, Boolean rings and quantum gates

    Science.gov (United States)

    Vourdas, A.

    2016-10-01

    Coherent spaces spanned by a finite number of coherent states, are introduced. Their coherence properties are studied, using the Dirac contour representation. It is shown that the corresponding projectors resolve the identity, and that they transform into projectors of the same type, under displacement transformations, and also under time evolution. The set of these spaces, with the logical OR and AND operations is a distributive lattice, and with the logical XOR and AND operations is a Boolean ring (Stone's formalism). Applications of this Boolean ring into classical CNOT gates with n-ary variables, and also quantum CNOT gates with coherent states, are discussed.

  15. Slime mould logical gates: exploring ballistic approach

    CERN Document Server

    Adamatzky, Andrew

    2010-01-01

    Plasmodium of \\emph{Physarum polycephalum} is a single cell visible by unaided eye. On a non-nutrient substrate the plasmodium propagates as a traveling localization, as a compact wave-fragment of protoplasm. The plasmodium-localization travels in its originally predetermined direction for a substantial period of time even when no gradient of chemo-attractants is present. We utilize this property of \\emph{Physarum} localizations to design a two-input two-output Boolean logic gates $ \\to $ and $ \\to $. We verify the designs in laboratory experiments and computer simulations. We cascade the logical gates into one-bit half-adder and simulate its functionality.

  16. Fidelity of adiabatic holonomic quantum gates

    Science.gov (United States)

    Malinovsky, Vladimir; Rudin, Sergey

    2016-05-01

    During last few years non-Abelian geometric phases are attracting increasing interest due to possible experimental applications in quantum computation. Here we discuss universal set of holonomic quantum gates using the geometric phase that the qubit wave function acquires after a cyclic evolution. The proposed scheme utilizes ultrafast pulses and provides a possibility to substantially suppress transient population of the ancillary states. Fidelity of the holonomic quantum gates in the presence of dephasing and dissipation is discussed. Example of electron spin qubit system in the InGaN/GaN, GaN/AlN quantum dot is considered in details.

  17. Gate Bias Effects on Samples with Edge Gates in the Quantum Hall Regime

    OpenAIRE

    若林 淳一; 風間 重雄; 長嶋 登志夫

    2001-01-01

    We have fabricated GaAs/AlGaAs heterostructure Hall samples that have edge gate with several widths along both sides of the sample. The gate width dependence of an effect of the gate voltage to the Hall resistance was measured at the middle of a transition region between the adjacent quantum Hall plateaus. The results have been analyzed based on two model functions of current distribution;an exponential type and the modified Beenakker type. The results of the former have shown qualitative agr...

  18. Improved Classical Simulation of Quantum Circuits Dominated by Clifford Gates.

    Science.gov (United States)

    Bravyi, Sergey; Gosset, David

    2016-06-24

    We present a new algorithm for classical simulation of quantum circuits over the Clifford+T gate set. The runtime of the algorithm is polynomial in the number of qubits and the number of Clifford gates in the circuit but exponential in the number of T gates. The exponential scaling is sufficiently mild that the algorithm can be used in practice to simulate medium-sized quantum circuits dominated by Clifford gates. The first demonstrations of fault-tolerant quantum circuits based on 2D topological codes are likely to be dominated by Clifford gates due to a high implementation cost associated with logical T gates. Thus our algorithm may serve as a verification tool for near-term quantum computers which cannot in practice be simulated by other means. To demonstrate the power of the new method, we performed a classical simulation of a hidden shift quantum algorithm with 40 qubits, a few hundred Clifford gates, and nearly 50 T gates.

  19. Sampling Number Effects in 2D and Range Imaging of Range-gated Acquisition

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Seong-Ouk; Park, Seung-Kyu; Baik, Sung-Hoon; Cho, Jai-Wan; Jeong, Kyung-Min [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    In this paper, we analyzed the number effects of sampling images for making a 2D image and a range image from acquired RGI images. We analyzed the number effects of RGI images for making a 2D image and a range image using a RGI vision system. As the results, 2D image quality was not much depended on the number of sampling images but on how much well extract efficient RGI images. But, the number of RGI images was important for making a range image because range image quality was proportional to the number of RGI images. Image acquiring in a monitoring area of nuclear industry is an important function for safety inspection and preparing appropriate control plans. To overcome the non-visualization problem caused by airborne obstacle particles, vision systems should have extra-functions, such as active illumination lightening through disturbance airborne particles. One of these powerful active vision systems is a range-gated imaging system. The vision system based on the range-gated imaging system can acquire image data from raining or smoking environments. Range-gated imaging (RGI) is a direct active visualization technique using a highly sensitive image sensor and a high intensity illuminant. Currently, the range-gated imaging technique providing 2D and 3D images is one of emerging active vision technologies. The range-gated imaging system gets vision information by summing time sliced vision images. In the RGI system, a high intensity illuminant illuminates for ultra-short time and a highly sensitive image sensor is gated by ultra-short exposure time to only get the illumination light. Here, the illuminant illuminates objects by flashing strong light through airborne disturbance particles. Thus, in contrast to passive conventional vision systems, the RGI active vision technology robust for low-visibility environments.

  20. Self-gated fat-suppressed cardiac cine MRI.

    Science.gov (United States)

    Ingle, R Reeve; Santos, Juan M; Overall, William R; McConnell, Michael V; Hu, Bob S; Nishimura, Dwight G

    2015-05-01

    To develop a self-gated alternating repetition time balanced steady-state free precession (ATR-SSFP) pulse sequence for fat-suppressed cardiac cine imaging. Cardiac gating is computed retrospectively using acquired magnetic resonance self-gating data, enabling cine imaging without the need for electrocardiogram (ECG) gating. Modification of the slice-select rephasing gradients of an ATR-SSFP sequence enables the acquisition of a one-dimensional self-gating readout during the unused short repetition time (TR). Self-gating readouts are acquired during every TR of segmented, breath-held cardiac scans. A template-matching algorithm is designed to compute cardiac trigger points from the self-gating signals, and these trigger points are used for retrospective cine reconstruction. The proposed approach is compared with ECG-gated ATR-SSFP and balanced steady-state free precession in 10 volunteers and five patients. The difference of ECG and self-gating trigger times has a variability of 13 ± 11 ms (mean ± SD). Qualitative reviewer scoring and ranking indicate no statistically significant differences (P > 0.05) between self-gated and ECG-gated ATR-SSFP images. Quantitative blood-myocardial border sharpness is not significantly different among self-gated ATR-SSFP ( 0.61±0.15 mm -1), ECG-gated ATR-SSFP ( 0.61±0.15 mm -1), or conventional ECG-gated balanced steady-state free precession cine MRI ( 0.59±0.15 mm -1). The proposed self-gated ATR-SSFP sequence enables fat-suppressed cardiac cine imaging at 1.5 T without the need for ECG gating and without decreasing the imaging efficiency of ATR-SSFP. © 2014 Wiley Periodicals, Inc.