Localization of Ca2+ -activated big-conductance K+ channels in rabbit distal colon

DEFF Research Database (Denmark)

Hay-Schmidt, Anders; Grunnet, Morten; Abrahamse, Salomon L

2003-01-01

Big-conductance Ca(2+)-activated K(+) channels (BK channels) may play an important role in the regulation of epithelial salt and water transport, but little is known about the expression level and the precise localization of BK channels in epithelia. The aim of the present study was to quantify a...

Volume Regulated Channels

DEFF Research Database (Denmark)

Klausen, Thomas Kjær

of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume...... but are also essential for a number of physiological processes such as proliferation, controlled cell death, migration and endocrinology. The thesis have been focusing on two Channels, namely the swelling activated Cl- channel (ICl, swell) and the transient receptor potential Vanilloid (TRPV4) channel. I: Cl......- serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...

Sediment transport and channel morphology of small, forested streams.

Science.gov (United States)

Marwan A. Hassan; Michael Church; Thomas E. Lisle; Francesco Brardinoni; Lee Benda; Gordon E. Grant

2005-01-01

This paper reviews sediment transport and channel morphology in small, forested streams in the Pacific Northwest region of North America to assess current knowledge of channel stability and morphology relevant to riparian management practices around small streams. Small channels are defined as ones in which morphology and hydraulics may be significantly influenced by...

Subcooled He II heat transport in the channel with abrupt contractions/enlargements

International Nuclear Information System (INIS)

Maekawa, R.; Iwamoto, A.; Hamaguchi, S.; Mito, T.

2002-01-01

Heat transport mechanisms for subcooled He II in the channel with abrupt contractions and/or enlargements have been investigated under steady state conditions. The channel, made of G-10, contains various contraction geometries to simulate the cooling channel of a superconducting magnet. In other words, contractions are periodically placed along the channel to simulate the spacers within the magnet winding. A copper block heater inputs the heat to the channel from one end, while the other end is open to the He II bath. Temperature profiles were measured with temperature sensors embedded in the channel as a function of heat input. Calculations were performed using a simple one-dimensional turbulent heat transport equation and with geometric factor consideration. The effects on heat transport mechanisms in He II caused by abrupt change of channel geometry and size are discussed

Creation and dynamical co-evolution of electron and ion channel transport barriers

International Nuclear Information System (INIS)

Newman, D.E.

2002-01-01

A wide variety of magnetic confinement devices have found transitions to an enhanced confinement regime. Simple dynamical models have been able to capture much of the dynamics of these barriers however an open question has been the disconnected nature of the electron thermal transport channel sometimes observed in the presence of a standard ('ion channel' barrier. By adding to simple barrier model an evolution equation for electron fluctuations we can investigate the interaction between the formation of the standard ion channel barrier and the somewhat less common electron channel barrier. Barrier formation in the electron channel is even more sensitive to the alignment of the various gradients making up the sheared radial electric field than the ion barrier is. Electron channel heat transport is found to significantly increase after the formation of the ion channel barrier but before the electron channel barrier is formed. This increased transport is important in the barrier evolution. (author)

Anisotropic transport of microalgae Chlorella vulgaris in microfluidic channel

International Nuclear Information System (INIS)

Ishak, Nur Izzati; Muniandy, S V; Periasamy, Vengadesh; Ng, Fong-Lee; Phang, Siew-Moi

2017-01-01

In this work, we study the regional dependence of transport behavior of microalgae Chlorella vulgaris inside microfluidic channel on applied fluid flow rate. The microalgae are treated as spherical naturally buoyant particles. Deviation from the normal diffusion or Brownian transport is characterized based on the scaling behavior of the mean square displacement (MSD) of the particle trajectories by resolving the displacements in the streamwise (flow) and perpendicular directions. The channel is divided into three different flow regions, namely center region of the channel and two near-wall boundaries and the particle motions are analyzed at different flow rates. We use the scaled Brownian motion to model the transitional characteristics in the scaling behavior of the MSDs. We find that there exist anisotropic anomalous transports in all the three flow regions with mixed sub-diffusive, normal and super-diffusive behavior in both longitudinal and transverse directions. (paper)

Fluid and solute transport in a network of channels

International Nuclear Information System (INIS)

Moreno, L.; Neretnieks, I.

1991-09-01

A three-dimensional channel network model is presented. The fluid flow and solute transport are assumed to take place through a network of connected channels. The channels are generated assuming that the conductances are lognormally distributed. The flow is calculated resolving the pressure distribution and the sole transport is calculated by using a particle tracking technique. The model includes diffusion into the rock matrix and sorption within the matrix in addition to advection along the channel network. Different approaches are used to describe the channel volume and its relation to the conductivity. To quantify the diffusion into the rock matrix the size of the flow wetted surface (contact surface between the channel and the rock) is needed in addition to the diffusion properties and the sorption capacity of the rock. Two different geometries were simulated: regional parallel flow and convergent flow toward a tunnel. In the generation of the channel network, it is found that its connectivity is reduced when the standard deviation in conductances is increased. For large standard deviations, the water conducting channels are found to be few. Standard deviations for the distribution of the effluent channel flowrates were calculated. Comparisons were made with experimental data from drifts and tunnels as well as boreholes as a means to validate the model. (au) (31 refs.)

Intermodal freight terminals : marketing channels and transport networks

NARCIS (Netherlands)

Nijkamp, Peter; Wiegmans, Bart

1999-01-01

The goal of this paper is to combine the current theory about marketing channels withcombined transport and logistics in order to develop a customer-based and broadly applicable approach to the study of combined freight transport inEurope. Furthermore, this paper seeks to provide an analytical

Transmural expression of ion channels and transporters in human nondiseased and end-stage failing hearts

DEFF Research Database (Denmark)

Soltysinska, Ewa; Olesen, Søren-Peter; Christ, Torsten

2009-01-01

The cardiac action potential is primarily shaped by the orchestrated function of several different types of ion channels and transporters. One of the regional differences believed to play a major role in the progression and stability of the action potential is the transmural gradient of electrica...... cardiac ion channels and transporters which may in part explain the increased susceptibility to arrhythmia in end-state failing hearts....... activity across the ventricular wall. An altered balance in the ionic currents across the free wall is assumed to be a substrate for arrhythmia. A large fraction of patients with heart failure experience ventricular arrhythmia. However, the underlying substrate of these functional changes is not well......-established as expression analyses of human heart failure (HF) are sparse. We have investigated steady-state RNA levels by quantitative polymerase chain reaction of ion channels, transporters, connexin 43, and miR-1 in 11 end-stage HF and seven nonfailing (NF) hearts. The quantifications were performed on endo-, mid...

Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

Science.gov (United States)

Marunaka, Yoshinori; Niisato, Naomi; Taruno, Akiyuki; Ohta, Mariko; Miyazaki, Hiroaki; Hosogi, Shigekuni; Nakajima, Ken-ichi; Kusuzaki, Katsuyuki; Ashihara, Eishi; Nishio, Kyosuke; Iwasaki, Yoshinobu; Nakahari, Takashi; Kubota, Takahiro

2011-01-01

Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane. PMID:22028593

Intermolecular Interactions in the TMEM16A Dimer Controlling Channel Activity.

Science.gov (United States)

Scudieri, Paolo; Musante, Ilaria; Gianotti, Ambra; Moran, Oscar; Galietta, Luis J V

2016-12-08

TMEM16A and TMEM16B are plasma membrane proteins with Ca 2+ -dependent Cl - channel function. By replacing the carboxy-terminus of TMEM16A with the equivalent region of TMEM16B, we obtained channels with potentiation of channel activity. Progressive shortening of the chimeric region restricted the "activating domain" to a short sequence close to the last transmembrane domain and led to TMEM16A channels with high activity at very low intracellular Ca 2+ concentrations. To elucidate the molecular mechanism underlying this effect, we carried out experiments based on double chimeras, Forster resonance energy transfer, and intermolecular cross-linking. We also modeled TMEM16A structure using the Nectria haematococca TMEM16 protein as template. Our results indicate that the enhanced activity in chimeric channels is due to altered interaction between the carboxy-terminus and the first intracellular loop in the TMEM16A homo-dimer. Mimicking this perturbation with a small molecule could be the basis for a pharmacological stimulation of TMEM16A-dependent Cl - transport.

Antisense oligonucleotides suppress cell-volume-induced activation of chloride channels.

Science.gov (United States)

Gschwentner, M; Nagl, U O; Wöll, E; Schmarda, A; Ritter, M; Paulmichl, M

1995-08-01

Cell volume regulation is an essential feature of most cells. After swelling in hypotonic media, the simultaneous activation of potassium and chloride channels is believed to be the initial, time-determining step in cell volume regulation. The activation of both pathways is functionally linked and enables the cells to lose ions and water, subsequently leading to cell shrinkage and readjustment of the initial volume. NIH 3T3 fibroblasts efficiently regulate their volume after swelling and bear chloride channels that are activated by decreasing extracellular osmolarity. The chloride current elicited in these cells after swelling is reminiscent of the current found in oocytes expressing an outwardly rectifying chloride current termed ICln. Introduction of antisense oligodeoxynucleotides complementary to the first 30 nucleotides of the coding region of the ICln channel into NIH 3T3 fibroblasts suppresses the activation of the swelling-induced chloride current. The experiments directly demonstrate an unambiguous link between a volume-activated chloride current and a cloned protein involved in chloride transport.

Activation of TRPV1 channels inhibits mechanosensitive Piezo channel activity by depleting membrane phosphoinositides

Science.gov (United States)

Borbiro, Istvan; Badheka, Doreen; Rohacs, Tibor

2015-01-01

Capsaicin is an activator of the heat-sensitive TRPV1 (transient receptor potential vanilloid 1) ion channels and has been used as a local analgesic. We found that activation of TRPV1 channels with capsaicin either in dorsal root ganglion neurons or in a heterologous expression system inhibited the mechanosensitive Piezo1 and Piezo2 channels by depleting phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and its precursor PI(4)P from the plasma membrane through Ca2+-induced phospholipase Cδ (PLCδ) activation. Experiments with chemically inducible phosphoinositide phosphatases and receptor-induced activation of PLCβ indicated that inhibition of Piezo channels required depletion of both PI(4)P and PI(4,5)P2. The mechanically activated current amplitudes decreased substantially in the excised inside-out configuration, where the membrane patch containing Piezo1 channels is removed from the cell. PI(4,5)P2 and PI(4)P applied to these excised patches inhibited this decrease. Thus, we concluded that Piezo channel activity requires the presence of phosphoinositides, and the combined depletion of PI(4,5)P2 or PI(4)P reduces channel activity. In addition to revealing a role for distinct membrane lipids in mechanosensitive ion channel regulation, these data suggest that inhibition of Piezo2 channels may contribute to the analgesic effect of capsaicin. PMID:25670203

Diagnostics of discharge channels for neutralized chamber transport in heavy ion fusion

International Nuclear Information System (INIS)

Niemann, C.; Penache, D.; Tauschwitz, A.; Rosmej, F.B.; Neff, S.; Birkner, R.; Constantin, C.; Knobloch, R.; Presura, R.; Yu, S.S.; Sharp, W.M.; Ponce, D.M.; Hoffmann, D.H.H.

2002-01-01

The final beam transport in the reactor chamber for heavy ion fusion in preformed plasma channels offers many attractive advantages compared to other transport modes. In the past few years, experiments at the Gesellschaft fuer Schwerionenforschung (GSI) accelerator facility have addressed the creation and investigation of discharge plasmas, designed for the transport of intense ion beams. Stable, self-standing channels of 50 cm length with currents up to 55 kA were initiated in low-pressure ammonia gas by a CO 2 -laser pulse along the channel axis before the discharge is triggered. The channels were characterized by several plasma diagnostics including interferometry and spectroscopy. We also present first experiments on laser-guided intersecting discharges

Active Brownian motion in a narrow channel

Science.gov (United States)

Ao, X.; Ghosh, P. K.; Li, Y.; Schmid, G.; Hänggi, P.; Marchesoni, F.

2014-12-01

We review recent advances in rectification control of artificial microswimmers, also known as Janus particles, diffusing along narrow, periodically corrugated channels. The swimmer self-propulsion mechanism is modeled so as to incorporate a nonzero torque (propulsion chirality). We first summarize the effects of chirality on the autonomous current of microswimmers freely diffusing in channels of different geometries. In particular, left-right and upside-down asymmetric channels are shown to exhibit different transport properties. We then report new results on the dependence of the diffusivity of chiral microswimmers on the channel geometry and their own self-propulsion mechanism. The self-propulsion torque turns out to play a key role as a transport control parameter.

Divalent Metal Ion Transport across Large Biological Ion Channels and Their Effect on Conductance and Selectivity

Directory of Open Access Journals (Sweden)

Elena García-Giménez

2012-01-01

Full Text Available Electrophysiological characterization of large protein channels, usually displaying multi-ionic transport and weak ion selectivity, is commonly performed at physiological conditions (moderate gradients of KCl solutions at decimolar concentrations buffered at neutral pH. We extend here the characterization of the OmpF porin, a wide channel of the outer membrane of E. coli, by studying the effect of salts of divalent cations on the transport properties of the channel. The regulation of divalent cations concentration is essential in cell metabolism and understanding their effects is of key importance, not only in the channels specifically designed to control their passage but also in other multiionic channels. In particular, in porin channels like OmpF, divalent cations modulate the efficiency of molecules having antimicrobial activity. Taking advantage of the fact that the OmpF channel atomic structure has been resolved both in water and in MgCl2 aqueous solutions, we analyze the single channel conductance and the channel selectivity inversion aiming to separate the role of the electrolyte itself, and the counterion accumulation induced by the protein channel charges and other factors (binding, steric effects, etc. that being of minor importance in salts of monovalent cations become crucial in the case of divalent cations.

Interactions Between Channel Topography and Hydrokinetic Turbines: Sediment Transport, Turbine Performance, and Wake Characteristics

Science.gov (United States)

Hill, Craig Steven

Accelerating marine hydrokinetic (MHK) renewable energy development towards commercial viability requires investigating interactions between the engineered environment and its surrounding physical and biological environments. Complex and energetic hydrodynamic and morphodynamic environments desired for such energy conversion installations present difficulties for designing efficient yet robust sustainable devices, while permitting agency uncertainties regarding MHK device environmental interactions result in lengthy and costly processes prior to installing and demonstrating emerging technologies. A research program at St. Anthony Falls Laboratory (SAFL), University of Minnesota, utilized multi-scale physical experiments to study the interactions between axial-flow hydrokinetic turbines, turbulent open channel flow, sediment transport, turbulent turbine wakes, and complex hydro-morphodynamic processes in channels. Model axial-flow current-driven three-bladed turbines (rotor diameters, dT = 0.15m and 0.5m) were installed in open channel flumes with both erodible and non-erodible substrates. Device-induced local scour was monitored over several hydraulic conditions and material sizes. Synchronous velocity, bed elevation and turbine performance measurements provide an indication into the effect channel topography has on device performance. Complimentary experiments were performed in a realistic meandering outdoor research channel with active sediment transport to investigate device interactions with bedform migration and secondary turbulent flow patterns in asymmetric channel environments. The suite of experiments undertaken during this research program at SAFL in multiple channels with stationary and mobile substrates under a variety of turbine configurations provides an in-depth investigation into how axial-flow hydrokinetic devices respond to turbulent channel flow and topographic complexity, and how they impact local and far-field sediment transport characteristics

Proton transport in a membrane protein channel: two-dimensional infrared spectrum modeling.

NARCIS (Netherlands)

Liang, C.; Knoester, J.; Jansen, T.L.Th.A.

2012-01-01

We model the two-dimensional infrared (2DIR) spectrum of a proton channel to investigate its applicability as a spectroscopy tool to study the proton transport process in biological systems. Proton transport processes in proton channels are involved in numerous fundamental biochemical reactions.

Tidal and meteorological forcing of sediment transport in tributary mudflat channels.

Science.gov (United States)

Ralston, David K; Stacey, Mark T

2007-06-01

Field observations of flow and sediment transport in a tributary channel through intertidal mudflats indicate that suspended sediment was closely linked to advection and dispersion of a tidal salinity front. During calm weather when tidal forcing was dominant, high concentrations of suspended sediment advected up the mudflat channel in the narrow region between salty water from San Francisco Bay and much fresher runoff from the small local watershed. Salinity and suspended sediment dispersed at similar rates through each tidal inundation, such that during receding ebbs the sediment pulse had spread spatially and maximum concentrations had decreased. Net sediment transport was moderately onshore during the calm weather, as asymmetries in stratification due to tidal straining of the salinity front enhanced deposition, particularly during weaker neap tidal forcing. Sediment transport by tidal forcing was periodically altered by winter storms. During storms, strong winds from the south generated wind waves and temporarily increased suspended sediment concentrations. Increased discharge down the tributary channels due to precipitation had more lasting impact on sediment transport, supplying both buoyancy and fine sediment to the system. Net sediment transport depended on the balance between calm weather tidal forcing and perturbations by episodic storms. Net transport in the tributary channel was generally off-shore during storms and during calm weather spring tides, and on-shore during calm weather neap tides.

Preliminary assessment of channel stability and bed-material transport along Hunter Creek, southwestern Oregon

Science.gov (United States)

Jones, Krista L.; Wallick, J. Rose; O'Connor, Jim E.; Keith, Mackenzie K.; Mangano, Joseph F.; Risley, John C.

2011-01-01

This preliminary assessment of (1) bed-material transport in the Hunter Creek basin, (2) historical changes in channel condition, and (3) supplementary data needed to inform permitting decisions regarding instream gravel extraction revealed the following: Along the lower 12.4 km (kilometers) of Hunter Creek from its confluence with the Little South Fork Hunter Creek to its mouth, the river has confined and unconfined segments and is predominately alluvial in its lowermost 11 km. This 12.4-km stretch of river can be divided into two geomorphically distinct study reaches based primarily on valley physiography. In the Upper Study Reach (river kilometer [RKM] 12.4-6), the active channel comprises a mixed bed of bedrock, boulders, and smaller grains. The stream is confined in the upper 1.4 km of the reach by a bedrock canyon and in the lower 2.4 km by its valley. In the Lower Study Reach (RKM 6-0), where the area of gravel bars historically was largest, the stream flows over bed material that is predominately alluvial sediments. The channel alternates between confined and unconfined segments. The primary human activities that likely have affected bed-material transport and the extent and area of gravel bars are (1) historical and ongoing aggregate extraction from gravel bars in the study area and (2) timber harvest and associated road construction throughout the basin. These anthropogenic activities likely have varying effects on sediment transport and deposition throughout the study area and over time. Although assessing the relative effects of these anthropogenic activities on sediment dynamics would be challenging, the Hunter Creek basin may serve as a case study for such an assessment because it is mostly free of other alterations to hydrologic and geomorphic processes such as flow regulation, dredging, and other navigation improvements that are common in many Oregon coastal basins. Several datasets are available that may support a more detailed physical assessment

Preliminary assessment of channel stability and bed-material transport in the Rogue River basin, southwestern Oregon

Science.gov (United States)

Jones, Krista L.; O'Connor, Jim E.; Keith, Mackenzie K.; Mangano, Joseph F.; Wallick, J. Rose

2012-01-01

This report summarizes a preliminary assessment of bed-material transport, vertical and lateral channel changes, and existing datasets for the Rogue River basin, which encompasses 13,390 square kilometers (km2) along the southwestern Oregon coast. This study, conducted to inform permitting decisions regarding instream gravel mining, revealed that: * The Rogue River in its lowermost 178.5 kilometers (km) alternates between confined and unconfined segments, and is predominately alluvial along its lowermost 44 km. The study area on the mainstem Rogue River can be divided into five reaches based on topography, hydrology, and tidal influence. The largely confined, active channel flows over bedrock and coarse bed material composed chiefly of boulders and cobbles in the Grants Pass (river kilometers [RKM] 178.5-152.8), Merlin (RKM 152.8-132.7), and Galice Reaches (RKM 132.7-43.9). Within these confined reaches, the channel contains few bars and has stable planforms except for locally wider segments such as the Brushy Chutes area in the Merlin Reach. Conversely, the active channel flows over predominately alluvial material and contains nearly continuous gravel bars in the Lobster Creek Reach (RKM 43.9-6.7). The channel in the Tidal Reach (RKM 6.7-0) is also alluvial, but tidally affected and unconfined until RKM 2. The Lobster Creek and Tidal Reaches contain some of the most extensive bar deposits within the Rogue River study area. * For the 56.6-km-long segment of the Applegate River included in this study, the river was divided into two reaches based on topography. In the Upper Applegate River Reach (RKM 56.6-41.6), the confined, active channel flows over alluvium and bedrock and has few bars. In the Lower Applegate River Reach (RKM 41.6-0), the active channel alternates between confined and unconfined segments, flows predominantly over alluvium, shifts laterally in unconfined sections, and contains more numerous and larger bars. * The 6.5-km segment of the lower

Monte Carlo simulation of ballistic transport in high-mobility channels

Energy Technology Data Exchange (ETDEWEB)

Sabatini, G; Marinchio, H; Palermo, C; Varani, L; Daoud, T; Teissier, R [Institut d' Electronique du Sud (CNRS UMR 5214) - Universite Montpellier II (France); Rodilla, H; Gonzalez, T; Mateos, J, E-mail: sabatini@ies.univ-montp2.f [Departamento de Fisica Aplicada - Universidad de Salamanca (Spain)

2009-11-15

By means of Monte Carlo simulations coupled with a two-dimensional Poisson solver, we evaluate directly the possibility to use high mobility materials in ultra fast devices exploiting ballistic transport. To this purpose, we have calculated specific physical quantities such as the transit time, the transit velocity, the free flight time and the mean free path as functions of applied voltage in InAs channels with different lengths, from 2000 nm down to 50 nm. In this way the transition from diffusive to ballistic transport is carefully described. We remark a high value of the mean transit velocity with a maximum of 14x10{sup 5} m/s for a 50 nm-long channel and a transit time shorter than 0.1 ps, corresponding to a cutoff frequency in the terahertz domain. The percentage of ballistic electrons and the number of scatterings as functions of distance are also reported, showing the strong influence of quasi-ballistic transport in the shorter channels.

Monte Carlo simulation of ballistic transport in high-mobility channels

International Nuclear Information System (INIS)

Sabatini, G; Marinchio, H; Palermo, C; Varani, L; Daoud, T; Teissier, R; Rodilla, H; Gonzalez, T; Mateos, J

2009-01-01

By means of Monte Carlo simulations coupled with a two-dimensional Poisson solver, we evaluate directly the possibility to use high mobility materials in ultra fast devices exploiting ballistic transport. To this purpose, we have calculated specific physical quantities such as the transit time, the transit velocity, the free flight time and the mean free path as functions of applied voltage in InAs channels with different lengths, from 2000 nm down to 50 nm. In this way the transition from diffusive to ballistic transport is carefully described. We remark a high value of the mean transit velocity with a maximum of 14x10 5 m/s for a 50 nm-long channel and a transit time shorter than 0.1 ps, corresponding to a cutoff frequency in the terahertz domain. The percentage of ballistic electrons and the number of scatterings as functions of distance are also reported, showing the strong influence of quasi-ballistic transport in the shorter channels.

Understanding transporter specificity and the discrete appearance of channel-like gating domains in transporters

Directory of Open Access Journals (Sweden)

GEORGE eDIALLINAS

2014-09-01

Full Text Available Transporters are ubiquitous proteins mediating the translocation of solutes across cell membranes, a biological process involved in nutrition, signaling, neurotransmission, cell communication and drug uptake or efflux. Similarly to enzymes, most transporters have a single substrate binding-site and thus their activity follows Michaelis-Menten kinetics. Substrate binding elicits a series of structural changes, which produce a transporter conformer open towards the side opposite to the one from where the substrate was originally bound. This mechanism, involving alternate outward- and inward-facing transporter conformers, has gained significant support from structural, genetic, biochemical and biophysical approaches. Most transporters are specific for a given substrate or a group of substrates with similar chemical structure, but substrate specificity and/or affinity can vary dramatically, even among members of a transporter family that show high overall amino acid sequence and structural similarity. The current view is that transporter substrate affinity or specificity is determined by a small number of interactions a given solute can make within a specific binding site. However, genetic, biochemical and in silico modeling studies with the purine transporter UapA of the filamentous ascomycete Aspergillus nidulans have challenged this dogma. This review highlights results leading to a novel concept, stating that substrate specificity, but also transport kinetics and transporter turnover, are determined by subtle intramolecular interactions between a major substrate binding site and independent outward- or cytoplasmically-facing gating domains, analogous to those present in channels. This concept is supported by recent structural evidence from several, phylogenetically and functionally distinct transporter families. The significance of this concept is discussed in relationship to the role and potential exploitation of transporters in drug action.

Water transport in graphene nano-channels

DEFF Research Database (Denmark)

Wagemann, Enrique; Oyarzua, Elton; Walther, J. H.

The transport of water in nanopores is of both fundamental and practical interest. Graphene Channels (GCs) are potential building blocks for nanofluidic devices dueto their molecularly smooth walls and exceptional mechanical properties. Numerous studies have found a significant flow rate enhancem......The transport of water in nanopores is of both fundamental and practical interest. Graphene Channels (GCs) are potential building blocks for nanofluidic devices dueto their molecularly smooth walls and exceptional mechanical properties. Numerous studies have found a significant flow rate...... between the chirality of the graphene walls and the slip length has not been established. In this study, we perform non-equilibrium molecular dynamics simulations of water flow in single- and multi-walled GCs. We examine the influence on the flow rates of dissipating the viscous heat produced...... by connecting the thermostat to the water molecules, the CNT wall atoms or both of them. From the atomic trajectories, we compute the fluid flow rates in GCs with zig-zag and armchair walls, heights from 1 to 4 nm and different number of graphene layers on the walls. A relation between the chirality, slip...

Sediment transport-storage relations for degrading, gravel bed channels

Science.gov (United States)

Thomas E. Lisle; Michael Church

2002-01-01

In a drainage network,sediment is transferred through a series of channel/valley segments (natural sediment storage reservoirs) that are distinguished from their neighbors by their particular capacity to store and transport sediment. We propose that the sediment transport capacity of each reservoir is a unique positive function of storage volume, which influences...

Glial and Neuronal Glutamate Transporters Differ in the Na+ Requirements for Activation of the Substrate-Independent Anion Conductance

Directory of Open Access Journals (Sweden)

Christopher B. Divito

2017-05-01

Full Text Available Excitatory amino acid transporters (EAATs are secondary active transporters of L-glutamate and L- or D-aspartate. These carriers also mediate a thermodynamically uncoupled anion conductance that is gated by Na+ and substrate binding. The activation of the anion channel by binding of Na+ alone, however, has only been demonstrated for mammalian EAAC1 (EAAT3 and EAAT4. To date, no difference has been observed for the substrate dependence of anion channel gating between the glial, EAAT1 and EAAT2, and the neuronal isoforms EAAT3, EAAT4 and EAAT5. Here we describe a difference in the Na+-dependence of anion channel gating between glial and neuronal isoforms. Chloride flux through transporters without glutamate binding has previously been described as substrate-independent or “leak” channel activity. Choline or N-methyl-D-glucamine replacement of external Na+ ions significantly reduced or abolished substrate-independent EAAT channel activity in EAAT3 and EAAT4 yet has no effect on EAAT1 or EAAT2. The interaction of Na+ with the neuronal carrier isoforms was concentration dependent, consistent with previous data. The presence of substrate and Na+-independent open states in the glial EAAT isoforms is a novel finding in the field of EAAT function. Our results reveal an important divergence in anion channel function between glial and neuronal glutamate transporters and highlight new potential roles for the EAAT-associated anion channel activity based on transporter expression and localization in the central nervous system.

Aluminum-Activated Malate Transporters Can Facilitate GABA Transport.

Science.gov (United States)

Ramesh, Sunita A; Kamran, Muhammad; Sullivan, Wendy; Chirkova, Larissa; Okamoto, Mamoru; Degryse, Fien; McLaughlin, Michael; Gilliham, Matthew; Tyerman, Stephen D

2018-05-01

Plant aluminum-activated malate transporters (ALMTs) are currently classified as anion channels; they are also known to be regulated by diverse signals, leading to a range of physiological responses. Gamma-aminobutyric acid (GABA) regulation of anion flux through ALMT proteins requires a specific amino acid motif in ALMTs that shares similarity with a GABA binding site in mammalian GABA A receptors. Here, we explore why TaALMT1 activation leads to a negative correlation between malate efflux and endogenous GABA concentrations ([GABA] i ) in both wheat ( Triticum aestivum ) root tips and in heterologous expression systems. We show that TaALMT1 activation reduces [GABA] i because TaALMT1 facilitates GABA efflux but GABA does not complex Al 3+ TaALMT1 also leads to GABA transport into cells, demonstrated by a yeast complementation assay and via 14 C-GABA uptake into TaALMT1 -expressing Xenopus laevis oocytes; this was found to be a general feature of all ALMTs we examined. Mutation of the GABA motif (TaALMT1 F213C ) prevented both GABA influx and efflux, and resulted in no correlation between malate efflux and [GABA] i We conclude that ALMTs are likely to act as both GABA and anion transporters in planta. GABA and malate appear to interact with ALMTs in a complex manner to regulate each other's transport, suggestive of a role for ALMTs in communicating metabolic status. © 2018 American Society of Plant Biologists. All rights reserved.

Kinetic Theory and Simulation of Single-Channel Water Transport

Science.gov (United States)

Tajkhorshid, Emad; Zhu, Fangqiang; Schulten, Klaus

Water translocation between various compartments of a system is a fundamental process in biology of all living cells and in a wide variety of technological problems. The process is of interest in different fields of physiology, physical chemistry, and physics, and many scientists have tried to describe the process through physical models. Owing to advances in computer simulation of molecular processes at an atomic level, water transport has been studied in a variety of molecular systems ranging from biological water channels to artificial nanotubes. While simulations have successfully described various kinetic aspects of water transport, offering a simple, unified model to describe trans-channel translocation of water turned out to be a nontrivial task.

Intracellular long-chain acyl CoAs activate TRPV1 channels.

Directory of Open Access Journals (Sweden)

Yi Yu

Full Text Available TRPV1 channels are an important class of membrane proteins that play an integral role in the regulation of intracellular cations such as calcium in many different tissue types. The anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2 is a known positive modulator of TRPV1 channels and the negatively charged phosphate groups interact with several basic amino acid residues in the proximal C-terminal TRP domain of the TRPV1 channel. We and other groups have shown that physiological sub-micromolar levels of long-chain acyl CoAs (LC-CoAs, another ubiquitous anionic lipid, can also act as positive modulators of ion channels and exchangers. Therefore, we investigated whether TRPV1 channel activity is similarly regulated by LC-CoAs. Our results show that LC-CoAs are potent activators of the TRPV1 channel and interact with the same PIP2-binding residues in TRPV1. In contrast to PIP2, LC-CoA modulation of TRPV1 is independent of Ca2+i, acting in an acyl side-chain saturation and chain-length dependent manner. Elevation of LC-CoAs in intact Jurkat T-cells leads to significant increases in agonist-induced Ca2+i levels. Our novel findings indicate that LC-CoAs represent a new fundamental mechanism for regulation of TRPV1 channel activity that may play a role in diverse cell types under physiological and pathophysiological conditions that alter fatty acid transport and metabolism such as obesity and diabetes.

Numerical Simulation of Flow and Suspended Sediment Transport in the Distributary Channel Networks

Directory of Open Access Journals (Sweden)

Wei Zhang

2014-01-01

Full Text Available Flow and suspended sediment transport in distributary channel networks play an important role in the evolution of deltas and estuaries, as well as the coastal environment. In this study, a 1D flow and suspended sediment transport model is presented to simulate the hydrodynamics and suspended sediment transport in the distributary channel networks. The governing equations for river flow are the Saint-Venant equations and for suspended sediment transport are the nonequilibrium transport equations. The procedure of solving the governing equations is firstly to get the matrix form of the water level and suspended sediment concentration at all connected junctions by utilizing the transformation of the governing equations of the single channel. Secondly, the water level and suspended sediment concentration at all junctions can be obtained by solving these irregular spare matrix equations. Finally, the water level, discharge, and suspended sediment concentration at each river section can be calculated. The presented 1D flow and suspended sediment transport model has been applied to the Pearl River networks and can reproduce water levels, discharges, and suspended sediment concentration with good accuracy, indicating this that model can be used to simulate the hydrodynamics and suspended sediment concentration in the distributary channel networks.

Suspended sediment transport trough a large fluvial-tidal channel network

Science.gov (United States)

Wright, Scott A.; Morgan-King, Tara L.

2015-01-01

The confluence of the Sacramento and San Joaquin Rivers, CA, forms a large network of interconnected channels, referred to as the Sacramento-San Joaquin Delta (the Delta). The Delta comprises the transition zone from the fluvial influences of the upstream rivers and tidal influences of San Francisco Bay downstream. Formerly an extensive tidal marsh, the hydrodynamics and geomorphology of Delta have been substantially modified by humans to support agriculture, navigation, and water supply. These modifications, including construction of new channels, diking and draining of tidal wetlands, dredging of navigation channels, and the operation of large pumping facilities for distribution of freshwater from the Delta to other parts of the state, have had a dramatic impact on the physical and ecological processes within the Delta. To better understand the current physical processes, and their linkages to ecological processes, the USGS maintains an extensive network of flow, sediment, and water quality gages in the Delta. Flow gaging is accomplished through use of the index-velocity method, and sediment monitoring uses turbidity as a surrogate for suspended-sediment concentration. Herein, we present analyses of the transport and dispersal of suspended sediment through the complex network of channels in the Delta. The primary source of sediment to the Delta is the Sacramento River, which delivers pulses of sediment primarily during winter and spring runoff events. Upon reaching the Delta, the sediment pulses move through the fluvial-tidal transition while also encountering numerous channel junctions as the Sacramento River branches into several distributary channels. The monitoring network allows us to track these pulses through the network and document the dominant transport pathways for suspended sediment. Further, the flow gaging allows for an assessment of the relative effects of advection (the fluvial signal) and dispersion (from the tides) on the sediment pulses as they

Channel-facilitated molecular transport: The role of strength and spatial distribution of interactions

Energy Technology Data Exchange (ETDEWEB)

Uppulury, Karthik, E-mail: karthik.uppulury@gmail.com [Department of Chemistry, Texas Tech University, Lubbock, TX 79409 (United States); Kolomeisky, Anatoly B. [Department of Chemistry, Department of Chemical and Biomolecular Engineering, Center for Theoretical Biological Physics, Rice University, Houston, TX 77005 (United States)

2016-12-20

Highlights: • Molecular flux strongly depends on the strength of the molecule-pore interactions. • There exists an optimal molecule-pore interaction potential for maximal flux. • Volume of interactions depends inversely on the strength for maximal flux. • Stronger interactions need more number of attractive sites for maximal flux. • Channels with few special sites need more attractive sites for higher flux. - Abstract: Molecular transport across channels and pores is critically important for multiple natural and industrial processes. Recent advances in single-molecule techniques have allowed researchers to probe translocation through nanopores with unprecedented spatial and temporal resolution. However, our understanding of the mechanisms of channel-facilitated molecular transport is still not complete. We present a theoretical approach that investigates the role of molecular interactions in the transport through channels. It is based on the discrete-state stochastic analysis that provides a fully analytical description of this complex process. It is found that a spatial distribution of the interactions strongly influences the translocation dynamics. We predict that there is the optimal distribution that leads to the maximal flux through the channel. It is also argued that the channel transport depends on the strength of the molecule-pore interactions, on the shape of interaction potentials and on the relative contributions of entrance and diffusion processes in the system. These observations are discussed using simple physical-chemical arguments.

Channel-facilitated molecular transport: The role of strength and spatial distribution of interactions

International Nuclear Information System (INIS)

Uppulury, Karthik; Kolomeisky, Anatoly B.

2016-01-01

Highlights: • Molecular flux strongly depends on the strength of the molecule-pore interactions. • There exists an optimal molecule-pore interaction potential for maximal flux. • Volume of interactions depends inversely on the strength for maximal flux. • Stronger interactions need more number of attractive sites for maximal flux. • Channels with few special sites need more attractive sites for higher flux. - Abstract: Molecular transport across channels and pores is critically important for multiple natural and industrial processes. Recent advances in single-molecule techniques have allowed researchers to probe translocation through nanopores with unprecedented spatial and temporal resolution. However, our understanding of the mechanisms of channel-facilitated molecular transport is still not complete. We present a theoretical approach that investigates the role of molecular interactions in the transport through channels. It is based on the discrete-state stochastic analysis that provides a fully analytical description of this complex process. It is found that a spatial distribution of the interactions strongly influences the translocation dynamics. We predict that there is the optimal distribution that leads to the maximal flux through the channel. It is also argued that the channel transport depends on the strength of the molecule-pore interactions, on the shape of interaction potentials and on the relative contributions of entrance and diffusion processes in the system. These observations are discussed using simple physical-chemical arguments.

Bedload transport in an inlet channel during a tidal cycle

DEFF Research Database (Denmark)

Ernstsen, V. B.; Becker, M.; Winter, C.

2007-01-01

  Based on high-resolution swath bathymetry measurements at centimetre-scale precision conducted during a tidal cycle in a dune field in the Grådyb tidal inlet channel in the DanishWadden Sea, a simple tool to calculate bedload transport is presented. Bedload transport was related to simultaneous...... variations in grain-size composition of the mobilised sediment should be taken into account by sediment transport formulae....

Entropic transport of active particles driven by a transverse ac force

Energy Technology Data Exchange (ETDEWEB)

Wu, Jian-chun, E-mail: wjchun2010@163.com; Chen, Qun; Ai, Bao-quan, E-mail: aibq@scnu.edu.cn

2015-12-18

Transport of active particles is numerically investigated in a two-dimensional period channel. In the presence of a transverse ac force, the directed transport of active particles demonstrates striking behaviors. By adjusting the amplitude and the frequency of the transverse ac force, the average velocity will be influenced significantly and the direction of the transport can be reversed several times. Remarkably, it is also found that the direction of the transport varies with different self-propelled speeds. Therefore, particles with different self-propelled speeds will move to the different directions, which is able to separate particles of different self-propelled speeds. - Highlights: • A transverse ac force strongly influence the transport of active particles. • The direction of the transport can be reversed several times. • Active particles with different self-propelled speeds can be separated.

Molecular dynamics simulation of continuous nanoflow transport through the uneven wettability channel

Science.gov (United States)

Zhang, Kai; Wang, Feng-hui; Lu, Yong-jun

2018-01-01

It is necessary to understand and predict the behavior of continuous nanoflow, especially inside the nanochannel with uneven wettability. Because the properties of fluid confined in the nanochannel are different from the macroscopic fluid, molecular level understanding is critical for future applications. In this work, a series of molecular dynamics simulations were executed to investigate the effect of the wettability gradient on the continuous nanofluid. In the simulations, different osmotic pressures were applied to make the water transport through different nanochannels. Simulation data was analyzed to obtain water flow rate, shear viscosity, capillary force, density distributions along the height directions of channel and apparent friction factor. Results show that the uneven wettability has a significant effect on the transportation of confined water only under the proper applied osmotic pressure and the height of channel. Under the appropriate conditions, the uneven wettability has a promotion on the transportation of water when it is at the exit of channel. When the uneven wettability locates in the entrance and middle of the channel, the uneven wettability will hinder the transportation of water. Especially, it is worth mentioning that there is a special phenomenon when the height of the nanochannel becomes 0.8 nm. Depending on the applied osmotic pressure, the uneven wettability has a double-sided effect on the confined fluid inside the channel with H = 0.8 nm. Our work may contribute to the design of nanochannels.

Investigation of the potential barrier lowering for quasi-ballistic transport in short channel MOSFETs

International Nuclear Information System (INIS)

Lee, Jaehong; Kwon, Yongmin; Ji, Junghwan; Shin, Hyungcheol

2011-01-01

In this paper, the quasi-ballistic carrier transport in short channel MOSFETs is investigated from the point of potential barrier lowering. To investigate the ballistic characteristic of transistors, we extracted the channel backscattering coefficient and the ballistic ratio from experimental data obtained by RF C-V and DC I-V measurements. Two factors that modulate the potential barrier height, besides the gate bias, are considered in this work: the drain bias (V DS ) and the channel doping concentration (N A ). We extract the critical length by calculating the potential drop in the channel region and conclude that the drain bias and the channel doping concentration affect the quasi-ballistic carrier transport.

Mechanisms of molecular transport through the urea channel of Helicobacter pylori

Science.gov (United States)

McNulty, Reginald; Ulmschneider, Jakob P.; Luecke, Hartmut; Ulmschneider, Martin B.

2013-12-01

Helicobacter pylori survival in acidic environments relies on cytoplasmic hydrolysis of gastric urea into ammonia and carbon dioxide, which buffer the pathogen’s periplasm. Urea uptake is greatly enhanced and regulated by HpUreI, a proton-gated inner membrane channel protein essential for gastric survival of H. pylori. The crystal structure of HpUreI describes a static snapshot of the channel with two constriction sites near the center of the bilayer that are too narrow to allow passage of urea or even water. Here we describe the urea transport mechanism at atomic resolution, revealed by unrestrained microsecond equilibrium molecular dynamics simulations of the hexameric channel assembly. Two consecutive constrictions open to allow conduction of urea, which is guided through the channel by interplay between conserved residues that determine proton rejection and solute selectivity. Remarkably, HpUreI conducts water at rates equivalent to aquaporins, which might be essential for efficient transport of urea at small concentration gradients.

Cl- channels of the gastric parietal cell that are active at low pH.

Science.gov (United States)

Cuppoletti, J; Baker, A M; Malinowska, D H

1993-06-01

HCl secretion across mammalian gastric parietal cell apical membrane may involve Cl- channels. H(+)-K(+)-ATPase-containing membranes isolated from gastric mucosa of histamine-stimulated rabbits were fused to planar lipid bilayers. Channels were recorded with symmetric 800 mM CsCl solutions, pH 7.4. A linear current-voltage (I-V) relationship was obtained, and conductance was 28 +/- 1 pS at 800 mM CsCl. Conductance was 6.9 +/- 2 pS at 150 mM CsCl. Reversal potential was +22 mV with a fivefold cis-trans CsCl concentration gradient, indicating that the channel was anion selective with a discrimination ratio of 6:1 for Cl- over Cs+. Anion selectivity of the channel was I- > Cl- > or = Br- > NO3-, and gluconate was impermeant. Channels obtained at pH 7.4 persisted when pH of medium bathing the trans side of the bilayer (pHtrans) was reduced to pH 3, without a change in conductance, linearity of I-V relationship, or ion selectivity. In contrast, asymmetric reduction of pH of medium bathing the cis side of the bilayer from 7.4 to 3 always resulted in loss of channel activity. At pH 7.4, open probability (Po) of the channel was voltage dependent, i.e., predominantly open at +80 mV but mainly closed at -80 mV. In contrast, with low pHtrans, channel Po at -80 mV was increased 3.5-fold. The Cl- channel was Ca2+ indifferent. In absence of ionophores, ion selectivity for support of H(+)-K(+)-ATPase activity and H+ transport was consistent with that exhibited by the channel and could be limited by substitution with NO3-, whereas maximal H(+)-K(+)-ATPase activity was indifferent to anion present, demonstrating that anion transport can be rate limiting. Cl- channels with similar characteristics (conductance, linear I-V relationship, and ion selectivity) were also present in H(+)-K(+)-ATPase-containing vesicles isolated from resting (cimetidine-treated) gastric mucosa, exhibiting at -80 mV a pH-independent approximately 3.5-fold lower Po than stimulated vesicle channels. At -80 m

Percolated microstructures for multi-modal transport enhancement in porous active materials

Energy Technology Data Exchange (ETDEWEB)

McKay, Ian Salmon; Yang, Sungwoo; Wang, Evelyn N.; Kim, Hyunho

2018-03-13

A method of forming a composite material for use in multi-modal transport includes providing three-dimensional graphene having hollow channels, enabling a polymer to wick into the hollow channels of the three-dimensional graphene, curing the polymer to form a cured three-dimensional graphene, adding an active material to the cured three-dimensional graphene to form a composite material, and removing the polymer from within the hollow channels. A composite material formed according to the method is also provided.

Pneumatic transport devices based on the ARS equipment set for activation analysis

International Nuclear Information System (INIS)

Ivanov, I.V.; Ivanets, V.N.; Rogachev, V.M.; Zakharov, E.A.

1978-01-01

The AGIDEL and ARS-28G facilities manufactured on the basis of a set of standardized and aggregated products for activation analysis are described. The AGIDEL is designed for automatic activation analysis of relatively homogeneous samples from oil boreholes. The ARS-28G is designed for transporting the test samples during activation analysis, using a fast-neutron generator. Structurally, the ARS-28 is based on a pneumatic transportation system with two independenhat transport cnnels and a two-channel rotating irradiation unit. The analyzed samples are transported in polyethylene containers, which are moved by compressed air. The facility has been successfully tested and is used in an automated system for multielement activation analysis

Channel change and bed-material transport in the Lower Chetco River, Oregon

Science.gov (United States)

Wallick, J. Rose; Anderson, Scott W.; Cannon, Charles; O'Connor, Jim E.

2010-01-01

The lower Chetco River is a wandering gravel-bed river flanked by abundant and large gravel bars formed of coarse bed-material sediment. Since the early twentieth century, the large gravel bars have been a source of commercial aggregate for which ongoing permitting and aquatic habitat concerns have motivated this assessment of historical channel change and sediment transport rates. Analysis of historical channel change and bed-material transport rates for the lower 18 kilometers shows that the upper reaches of the study area are primarily transport zones, with bar positions fixed by valley geometry and active bars mainly providing transient storage of bed material. Downstream reaches, especially near the confluence of the North Fork Chetco River, are zones of active sedimentation and channel migration.Multiple analyses, supported by direct measurements of bedload during winter 2008–09, indicate that since 1970 the mean annual flux of bed material into the study reach has been about 40,000–100,000 cubic meters per year. Downstream tributary input of bed-material sediment, probably averaging 5–30 percent of the influx coming into the study reach from upstream, is approximately balanced by bed-material attrition by abrasion. Probably little bed material leaves the lower river under natural conditions, with most net influx historically accumulating in wider and more dynamic reaches, especially near the North Fork Chetco River confluence, 8 kilometers upstream from the Pacific Ocean.The year-to-year flux, however, varies tremendously. Some years may have less than 3,000 cubic meters of bed material entering the study area; by contrast, some high-flow years, such as 1982 and 1997, likely have more than 150,000 cubic meters entering the reach. For comparison, the estimated annual volume of gravel extracted from the lower Chetco River for commercial aggregate during 2000–2008 has ranged from 32,000 to 90,000 cubic meters and averaged about 59,000 cubic meters per

Carbonate Channel-Levee Systems Influenced by Mass-Transport Deposition, Browse Basin, Australia

Science.gov (United States)

Dunlap, D.; Janson, X.; Sanchez-Phelps, C.; Covault, J. A.

2017-12-01

Submarine channels are primary conduits for clastic sediment transport to deep-water basins, thereby controlling the location of marine depocenters and sediment bypass. The evolution and depositional character of submarine channels have broad implications to sediment dispersal, sediment quality, and hydrocarbon exploration potential. Siliciclastic channel systems have been extensively studied in modern environments, seismic and outcrop; however, carbonate channel-levee deposits have only recently been explored. Here we utilize newly released high-resolution (90 Hz) seismic-reflection data from the Australian Browse Basin to document the influence of mass-transport complex (MTC) deposition on the stratigraphic architecture of carbonate channel-levee systems. The 2014 vintage seismic survey is 2500 km2 and hosts numerous large Miocene-age carbonate channel-levee complexes basinward of the shelf edge. Regional horizons and individual channel forms were mapped. Channels range from 200-300 m wide and are bounded by high-relief levee-overbank wedges (>100 ms TWTT). These channels extend across the survey area >70 km. The leveed-channels were sourced from middle and late Miocene slope gullies linked to platform carbonates. Slope-attached and locally derived MTC's are evident throughout the Miocene section likely related to periods of basin inversion and shelf-edge gully incision. We interpret that regionally extensive (>1000 km2) slope-attached MTC's can shut down a channel-levee system and trigger the initiation of a new system, whereas more locally derived (wasting and turbidity currents, which informs depositional models of carbonate slope systems and calls for re-evaluation of the controls on stratigraphic patterns in mixed siliciclastic-carbonate deep-water basins.

The overview of channels, transporters, and calcium signaling molecules during amelogenesis.

Science.gov (United States)

Kim, Hee-Eun; Hong, Jeong Hee

2018-05-20

Enamel is a highly calcified tissue. Its formation requires a progressive and dynamic system for the regulation of electrolyte concentration by enamel epithelia. A critical function of enamel epithelial cells, ameloblasts, is the secretion and movement of electrolytes via various channels and transporters to develop the enamel tissue. Enamel formation generates protons, which need to be neutralised. Thus, ameloblasts possess a buffering system to sustain mineral accretion. Normal tooth formation involves stage-dependent net fluctuations in pH during amelogenesis. To date, all of our information about ion transporters in dental enamel tissue is based solely on immunostaining-expression techniques. This review critically evaluates the current understanding and recent discoveries and physiological role of ion channels and transporters, Mg 2+ transporters, and Ca 2+ regulatory proteins during amelogenesis in enamel formation. The ways in which ameloblasts modulate ions are discussed in the context of current research for developing a novel morphologic-functional model of enamel maturation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mechanisms of the 40-70 Day Variability in the Yucatan Channel Volume Transport

Science.gov (United States)

van Westen, René M.; Dijkstra, Henk A.; Klees, Roland; Riva, Riccardo E. M.; Slobbe, D. Cornelis; van der Boog, Carine G.; Katsman, Caroline A.; Candy, Adam S.; Pietrzak, Julie D.; Zijlema, Marcel; James, Rebecca K.; Bouma, Tjeerd J.

2018-02-01

The Yucatan Channel connects the Caribbean Sea with the Gulf of Mexico and is the main outflow region of the Caribbean Sea. Moorings in the Yucatan Channel show high-frequent variability in kinetic energy (50-100 days) and transport (20-40 days), but the physical mechanisms controlling this variability are poorly understood. In this study, we show that the short-term variability in the Yucatan Channel transport has an upstream origin and arises from processes in the North Brazil Current. To establish this connection, we use data from altimetry and model output from several high resolution global models. A significant 40-70 day variability is found in the sea surface height in the North Brazil Current retroflection region with a propagation toward the Lesser Antilles. The frequency of variability is generated by intrinsic processes associated with the shedding of eddies, rather than by atmospheric forcing. This sea surface height variability is able to pass the Lesser Antilles, it propagates westward with the background ocean flow in the Caribbean Sea and finally affects the variability in the Yucatan Channel volume transport.

Targeting channels and transporters in protozoan parasite infections

Science.gov (United States)

Meier, Anna; Erler, Holger; Beitz, Eric

2018-03-01

Infectious diseases caused by pathogenic protozoa are among the most significant causes of death in humans. Therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains. Many of the current anti-parasite drugs target soluble enzymes, generate unspecific oxidative stress, or act by an unresolved mechanism within the parasite. In recent years, collections of drug-like compounds derived from large-scale phenotypic screenings, such as the malaria or pathogen box, have been made available to researchers free of charge boosting the identification of novel promising targets. Remarkably, several of the compound hits have been found to inhibit membrane proteins at the periphery of the parasites, i.e. channels and transporters for ions and metabolites. In this review, we will focus on the progress made on targeting channels and transporters at different levels and the potential for use against infections with apicomplexan parasites mainly Plasmodium spp. (malaria) and Toxoplasma gondii (toxoplasmosis), with kinetoplastids Trypanosoma brucei (sleeping sickness), Trypanosoma cruzi (Chagas disease) and Leishmania ssp. (leishmaniasis), and the amoeba Entamoeba histolytica (amoebiasis).

Ionic channels in plants: potassium transport Canais iônicos em plantas: o transporte de potássio

Directory of Open Access Journals (Sweden)

Antonio Costa de Oliveira

1995-01-01

Full Text Available The discovery of potassium channels on the plasma membrane has helped to elucidate important mechanisms in animal and plant physiology. Plant growth and development associated mechanisms, such as germination, leaf movements, stomatal action, ion uptake in roots, phloem transport and nutrient storage are linked to potassium transport. Studies describing potassium transport regulation by abscisic acid (ABA, Ca++, light and other factors are presented here. Also the types of channels that regulate potassium uptake and efflux in the cell, and the interaction of these channels with external signals, are discussed.A descoberta de canais iônicos presentes na membrana plasmática tem ajudado a elucidar importantes mecanismos fisiológicos em animais e plantas. Mecanismos associados ao crescimento e desenvolvimento das plantas, tais como germinação, movimento foliar, abertura e fechamento de estômatos, absorção de íons pelas raízes e armazenamento de nutrientes estão ligados ao transporte de potássio. Estudos descrevendo a regulação do transporte deste nutriente por ácido abscísico (ABA, Ca++, luz e outros fatores são apresentados. Os tipos de canais que regulam a saída e entrada de potássio na célula, e as interações destes com os sinais externos, são discutidos.

Transport or Store? Synthesizing Flow-based Microfluidic Biochips using Distributed Channel Storage

DEFF Research Database (Denmark)

Liu, Chunfeng; Li, Bing; Yao, Hailong

2017-01-01

of the performance of biochips. In this paper, we propose the first architectural synthesis framework considering distributed storage constructed temporarily from transportation channels to cache fluid samples. Since distributed storage can be accessed more efficiently than a dedicated storage unit and channels can...... switch between the roles of transportation and storage easily, biochips with this distributed computing architecture can achieve a higher execution efficiency even with fewer resources. Experimental results confirm that the execution efficiency of a bioassay can be improved by up to 28% while the number...

Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex.

Directory of Open Access Journals (Sweden)

Weiping Zhang

Full Text Available Calcium-activated chloride channels of the anoctamin (alias TMEM16 protein family fulfill critical functions in epithelial fluid transport, smooth muscle contraction and sensory signal processing. Little is known, however, about their contribution to information processing in the central nervous system. Here we examined the recent finding that a calcium-dependent chloride conductance impacts on GABAergic synaptic inhibition in Purkinje cells of the cerebellum. We asked whether anoctamin channels may underlie this chloride conductance. We identified two anoctamin channel proteins, ANO1 and ANO2, in the cerebellar cortex. ANO1 was expressed in inhibitory interneurons of the molecular layer and the granule cell layer. Both channels were expressed in Purkinje cells but, while ANO1 appeared to be retained in the cell body, ANO2 was targeted to the dendritic tree. Functional studies confirmed that ANO2 was involved in a calcium-dependent mode of ionic plasticity that reduces the efficacy of GABAergic synapses. ANO2 channels attenuated GABAergic transmission by increasing the postsynaptic chloride concentration, hence reducing the driving force for chloride influx. Our data suggest that ANO2 channels are involved in a Ca2+-dependent regulation of synaptic weight in GABAergic inhibition. Thus, in balance with the chloride extrusion mechanism via the co-transporter KCC2, ANO2 appears to regulate ionic plasticity in the cerebellum.

Hybrid sediment transport model for the “linguado” channel, state of Santa Catarina, Brazil

Directory of Open Access Journals (Sweden)

Edison Conde Perez dos Santos

2017-12-01

Full Text Available This study involves an assessment of various artificial intelligence-related techniques which aim to produce a more robust system for sediment transport modeling. The intelligent systems developed in this research are directly applicable to academic knowledge and use data from a report on "water circulation assessment in the “Linguado” Channel and Babitonga Bay ,”Santa Catarina”, Brazil, developed by  Military Engineering Institute (IME. The solution employed for sediment transport was built using an intelligent system from the conception of two hybrid models. The first was a Neuro-Fuzzy (ANFIS hybrid model for the study of hydrodynamic behavior, aiming to determine flow rate in the channel. The second was a fuzzy genetic model, able to assess sediment transport in the “Linguado” Channel. The study's conclusion compares the different effects involved in the dredging equilibrium in the “Linguado” Channel according to this hybrid model with the results obtained using a finite element model in the MIKE21® software.

Hydrogen sulfide: role in ion channel and transporter modulation in the eye

Directory of Open Access Journals (Sweden)

Ya Fatou eNjie-Mbye

2012-07-01

Full Text Available Hydrogen sulfide (H2S, a colorless gas with a characteristic smell of rotten eggs, has been portrayed for decades as a toxic environmental pollutant. Since evidence of its basal production in mammalian tissues a decade ago, H2S has attracted substantial interest as a potential inorganic gaseous mediator with biological importance in cellular functions. Current research suggests that, next to its counterparts nitric oxide and carbon monoxide, H2S is an important multifunctional signaling molecule with pivotal regulatory roles in various physiological and pathophysiological processes as diverse as learning and memory, modulation of synaptic activities, cell survival, inflammation and maintenance of vascular tone in the central nervous and cardiovascular systems. In contrast, there are few reports of a regulatory role of H2S in the eye. Accumulating reports on the pharmacological role of H2S in ocular tissues indicate the existence of a functional trans-sulfuration pathway and a potential physiological role for H2S as a gaseous neuromodulator in the eye. Thus, understanding the role of H2S in vision-related processes is imperative to our expanding knowledge of this molecule as a gaseous mediator in ocular tissues. This review aims to provide a comprehensive and current understanding of the potential role of H2S as a signaling molecule in the eye. This objective is achieved by discussing the involvement of H2S in the regulation of (1 ion channels such as calcium (L-type, T-type and intracellular stores, potassium (KATP and small conductance channels and chloride channels, (2 glutamate transporters such as EAAT1/GLAST and the L-cystine/glutamate antiporter. The role of H2S as an important mediator in cellular functions and physiological processes that are triggered by its interaction with ion channels/transporters in the eye will also be discussed.

A fundamental study of ''contribution'' transport theory and channel theory applications

International Nuclear Information System (INIS)

Williams, M.L.

1992-01-01

The objective of this three-year study is to develop a technique called ''channel theory'' that can be used in interpreting particle transport analysis such as frequently required in radiation shielding design and assessment. Channel theory is a technique used to provide insight into the mechanisms by which particles emitted from a source are transported through a complex system and register a response on some detector. It is based on the behavior of a pseudo particle called a ''contributon,'' which is the response carrier through space and energy channels that connect the source and detector. ''Contributons'' are those particles among all the ones contained in the system which will eventually contribute some amount of response to the detector. The specific goals of this projects are to provide a more fundamental theoretical understanding of the method, and to develop computer programs to apply the techniques to practical problems encountered in radiation transport analysis. The overall project can be divided into three components to meet these objectives: (a) Theoretical Development, (b) Code Development, and (c) Sample Applications. During the present third year of this study, an application of contributon theory to the analysis of radiation heating in a nuclear rocket has been completed, and a paper on the assessment of radiation damage response of an LWR pressure vessel and analysis of radiation propagation through space and energy channels in air at the Hiroshima weapon burst was accepted for publication. A major effort was devoted to developing a new ''Contributon Monte Carlo'' method, which can improve the efficiency of Monte Carlo calculations of radiation transport by tracking only contributons. The theoretical basis for Contributon Monte Carlo has been completed, and the implementation and testing of the technique is presently being performed

Modeling of Particle Transport on Channels and Gaps Exposed to Plasma Fluxes

International Nuclear Information System (INIS)

Nieto-Perez, Martin

2008-01-01

Many problems in particle transport in fusion devices involve the transport of plasma or eroded particles through channels or gaps, such as in the case of trying to assess damage to delicate optical diagnostics collecting light through a slit or determining the deposition and codeposition on the gaps between tiles of plasma-facing components. A dynamic-composition Monte Carlo code in the spirit of TRIDYN, previously developed to study composition changes on optical mirrors subject to ion bombardment, has been upgraded to include motion of particles through a volume defined by sets of plane surfaces. Particles sputtered or reflected from the walls of the channel/gap can be tracked as well, allowing the calculation of wall impurity transport, either back to the plasma (for the case of a gap) or to components separated from the plasma by a channel/slit (for the case of optical diagnostics). Two examples of the code application to particle transport in fusion devices will be presented in this work: one will evaluate the erosion/impurity deposition rate on a mirror separated from a plasma source by a slit; the other case will look at the enhanced emission of tile material in the region of the gap between two tiles

Additional transport channel of carbon ions for biological research at the Nuclotron of JINR

International Nuclear Information System (INIS)

Yudin, I.P.; Panasik, V.A.; Tyutyunnikov, S.I.

2011-01-01

The paper deals with the construction of the 12 C +6 beam transport line for biomedical research at the Nuclotron accelerator complex, JINR. We have studied the scheme and modes of magneto-optical elements of the channel. The results of calculations of the investigated beam transport of carbon ions are presented. The algorithms to control the carbon ion beam in the transportation system are discussed. The choice of the magneto-optical system is motivated. The graphs of the beam envelopes in the channel are given. The scanning control beam functions are considered

Additional transport channel of carbon ions for biological research at the Nuclotron of JINR

International Nuclear Information System (INIS)

Yudin, I.P.; Panasik, V.A.; Tyutyunnikov, S.I.

2012-01-01

The paper deals with the construction of the beam 12 C +6 transport line for biomedical research at the Nuclotron accelerator complex, JINR. We have studied the scheme and modes of magneto-optical elements of the channel. The results of calculations of the investigated beam transport of carbon ions are presented. The algorithms to control the carbon ion beam in the transportation system are discussed. The choice of the magneto-optical system is motivated. The graphs of the beam envelopes in the channel are given. The scanning control beam functions are considered

SLITHER: a web server for generating contiguous conformations of substrate molecules entering into deep active sites of proteins or migrating through channels in membrane transporters.

Science.gov (United States)

Lee, Po-Hsien; Kuo, Kuei-Ling; Chu, Pei-Ying; Liu, Eric M; Lin, Jung-Hsin

2009-07-01

Many proteins use a long channel to guide the substrate or ligand molecules into the well-defined active sites for catalytic reactions or for switching molecular states. In addition, substrates of membrane transporters can migrate to another side of cellular compartment by means of certain selective mechanisms. SLITHER (http://bioinfo.mc.ntu.edu.tw/slither/or http://slither.rcas.sinica.edu.tw/) is a web server that can generate contiguous conformations of a molecule along a curved tunnel inside a protein, and the binding free energy profile along the predicted channel pathway. SLITHER adopts an iterative docking scheme, which combines with a puddle-skimming procedure, i.e. repeatedly elevating the potential energies of the identified global minima, thereby determines the contiguous binding modes of substrates inside the protein. In contrast to some programs that are widely used to determine the geometric dimensions in the ion channels, SLITHER can be applied to predict whether a substrate molecule can crawl through an inner channel or a half-channel of proteins across surmountable energy barriers. Besides, SLITHER also provides the list of the pore-facing residues, which can be directly compared with many genetic diseases. Finally, the adjacent binding poses determined by SLITHER can also be used for fragment-based drug design.

Transport of long-pulse relativistic electron beams in preformed plasma channels in the ion focus regime

International Nuclear Information System (INIS)

Miller, J.D.

1989-01-01

Experiments have been performed demonstrating efficient transport of long-pulse (380 ns), high-current (200 A), relativistic electron beams (REBs) in preformed plasma channels in the ion focus regime (IFR). Plasma channels were created by low-energy ( e , and channel ion mass, in agreement with theoretical values predicted for the ion hose instability. Microwave emission has also been observed indicative of REB-plasma electron two-stream instability. Plasma channel density measurements indicate that the two-stream instability can become dominant for measured f e values slightly above unity. The author has introduced a theoretical analysis for high-current REB transport and modulation in axially periodic IFR plasma channels. Analytic expression for the electric field are found for the case of a cosine modulation of the channel ion density. Two different types of channels are considered: (i) periodic beam-induced ionization channels, and (ii) periodic plasma slab channels created by an external source. Analytical conditions are derived for the matched radius of the electron beam and for approximate beam envelope motion using a 'smooth' approximation. Numerical solutions to the envelope equation show that by changing the wavelength or the amplitude of the space-charge neutralization fraction of the ion channel density modulation, the beam can be made to focus and diverge, or to undergo stable, modulated transport

User's Guide for Mixed-Size Sediment Transport Model for Networks of One-Dimensional Open Channels

Science.gov (United States)

Bennett, James P.

2001-01-01

This user's guide describes a mathematical model for predicting the transport of mixed sizes of sediment by flow in networks of one-dimensional open channels. The simulation package is useful for general sediment routing problems, prediction of erosion and deposition following dam removal, and scour in channels at road embankment crossings or other artificial structures. The model treats input hydrographs as stepwise steady-state, and the flow computation algorithm automatically switches between sub- and supercritical flow as dictated by channel geometry and discharge. A variety of boundary conditions including weirs and rating curves may be applied both external and internal to the flow network. The model may be used to compute flow around islands and through multiple openings in embankments, but the network must be 'simple' in the sense that the flow directions in all channels can be specified before simulation commences. The location and shape of channel banks are user specified, and all bedelevation changes take place between these banks and above a user-specified bedrock elevation. Computation of sediment-transport emphasizes the sand-size range (0.0625-2.0 millimeter) but the user may select any desired range of particle diameters including silt and finer (user may set the original bed-sediment composition of any number of layers of known thickness. The model computes the time evolution of total transport and the size composition of bed- and suspended-load sand through any cross section of interest. It also tracks bed -surface elevation and size composition. The model is written in the FORTRAN programming language for implementation on personal computers using the WINDOWS operating system and, along with certain graphical output display capability, is accessed from a graphical user interface (GUI). The GUI provides a framework for selecting input files and parameters of a number of components of the sediment-transport process. There are no restrictions in the

Slack, Slick, and Sodium-Activated Potassium Channels

Science.gov (United States)

Kaczmarek, Leonard K.

2013-01-01

The Slack and Slick genes encode potassium channels that are very widely expressed in the central nervous system. These channels are activated by elevations in intracellular sodium, such as those that occur during trains of one or more action potentials, or following activation of nonselective cationic neurotransmitter receptors such as AMPA receptors. This review covers the cellular and molecular properties of Slack and Slick channels and compares them with findings on the properties of sodium-activated potassium currents (termed KNa currents) in native neurons. Human mutations in Slack channels produce extremely severe defects in learning and development, suggesting that KNa channels play a central role in neuronal plasticity and intellectual function. PMID:24319675

Sulina and Danube-Black Sea Channels: Competitors or Allies on Cargo Transport in South-Eastern Europe?

Directory of Open Access Journals (Sweden)

Ionica Soare

2015-10-01

Full Text Available The two river channels which connect the Black Sea to the inland Romanian area, have constituted since the beginning of their building two very important transport routes for the cargo and passenger traffic (Sulina that have connected Black Sea to the internal ports of Romania, thus representing ”transport highways” of the Romanian economy. The present study tries to present the chronological evolution of these two shipping routes, regarding their importance to the cargo traffic, as well as the financial policy imposed by the administration of these channels. We will present and analyze retrospectively the major elements regarding the administration of these channels, a comparative analysis of the role of these two channels in the river cargo transport, consequently trying to predict a future evolution of these two river communication routes.

A quantized mechanism for activation of pannexin channels

Science.gov (United States)

Chiu, Yu-Hsin; Jin, Xueyao; Medina, Christopher B.; Leonhardt, Susan A.; Kiessling, Volker; Bennett, Brad C.; Shu, Shaofang; Tamm, Lukas K.; Yeager, Mark; Ravichandran, Kodi S.; Bayliss, Douglas A.

2017-01-01

Pannexin 1 (PANX1) subunits form oligomeric plasma membrane channels that mediate nucleotide release for purinergic signalling, which is involved in diverse physiological processes such as apoptosis, inflammation, blood pressure regulation, and cancer progression and metastasis. Here we explore the mechanistic basis for PANX1 activation by using wild type and engineered concatemeric channels. We find that PANX1 activation involves sequential stepwise sojourns through multiple discrete open states, each with unique channel gating and conductance properties that reflect contributions of the individual subunits of the hexamer. Progressive PANX1 channel opening is directly linked to permeation of ions and large molecules (ATP and fluorescent dyes) and occurs during both irreversible (caspase cleavage-mediated) and reversible (α1 adrenoceptor-mediated) forms of channel activation. This unique, quantized activation process enables fine tuning of PANX1 channel activity and may be a generalized regulatory mechanism for other related multimeric channels. PMID:28134257

Channel sialic acids limit hERG channel activity during the ventricular action potential.

Science.gov (United States)

Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

2013-02-01

Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

Amiloride-Sensitive Sodium Channels and Pulmonary Edema

Directory of Open Access Journals (Sweden)

Mike Althaus

2011-01-01

Full Text Available The development of pulmonary edema can be considered as a combination of alveolar flooding via increased fluid filtration, impaired alveolar-capillary barrier integrity, and disturbed resolution due to decreased alveolar fluid clearance. An important mechanism regulating alveolar fluid clearance is sodium transport across the alveolar epithelium. Transepithelial sodium transport is largely dependent on the activity of sodium channels in alveolar epithelial cells. This paper describes how sodium channels contribute to alveolar fluid clearance under physiological conditions and how deregulation of sodium channel activity might contribute to the pathogenesis of lung diseases associated with pulmonary edema. Furthermore, sodium channels as putative molecular targets for the treatment of pulmonary edema are discussed.

Channel change and bed-material transport in the Umpqua River basin, Oregon

Science.gov (United States)

Wallick, J. Rose; O'Connor, Jim E.; Anderson, Scott; Keith, Mackenzie K.; Cannon, Charles; Risley, John C.

2011-01-01

The Umpqua River drains 12,103 square kilometers of western Oregon; with headwaters in the Cascade Range, the river flows through portions of the Klamath Mountains and Oregon Coast Range before entering the Pacific Ocean. Above the head of tide, the Umpqua River, along with its major tributaries, the North and South Umpqua Rivers, flows on a mixed bedrock and alluvium bed, alternating between bedrock rapids and intermittent, shallow gravel bars composed of gravel to cobble-sized clasts. These bars have been a source of commercial aggregate since the mid-twentieth century. Below the head of tide, the Umpqua River contains large bars composed of mud and sand. Motivated by ongoing permitting and aquatic habitat concerns related to in-stream gravel mining on the fluvial reaches, this study evaluated spatial and temporal trends in channel change and bed-material transport for 350 kilometers of river channel along the Umpqua, North Umpqua, and South Umpqua Rivers. The assessment produced (1) detailed mapping of the active channel, using aerial photographs and repeat surveys, and (2) a quantitative estimation of bed-material flux that drew upon detailed measurements of particle size and lithology, equations of transport capacity, and a sediment yield analysis. Bed-material transport capacity estimates at 45 sites throughout the South Umpqua and main stem Umpqua Rivers for the period 1951-2008 result in wide-ranging transport capacity estimates, reflecting the difficulty of applying equations of bed-material transport to a supply-limited river. Median transport capacity values calculated from surface-based equations of bedload transport for each of the study reaches provide indications of maximum possible transport rates and range from 8,000 to 27,000 metric tons per year (tons/yr) for the South Umpqua River and 20,000 to 82,000 metric tons/yr for the main stem Umpqua River upstream of the head of tide; the North Umpqua River probably contributes little bed material. A

Scaling relationships between bed load volumes, transport distances, and stream power in steep mountain channels

Science.gov (United States)

Schneider, Johannes M.; Turowski, Jens M.; Rickenmann, Dieter; Hegglin, Ramon; Arrigo, Sabrina; Mao, Luca; Kirchner, James W.

2014-03-01

Bed load transport during storm events is both an agent of geomorphic change and a significant natural hazard in mountain regions. Thus, predicting bed load transport is a central challenge in fluvial geomorphology and natural hazard risk assessment. Bed load transport during storm events depends on the width and depth of bed scour, as well as the transport distances of individual sediment grains. We traced individual gravels in two steep mountain streams, the Erlenbach (Switzerland) and Rio Cordon (Italy), using magnetic and radio frequency identification tags, and measured their bed load transport rates using calibrated geophone bed load sensors in the Erlenbach and a bed load trap in the Rio Cordon. Tracer transport distances and bed load volumes exhibited approximate power law scaling with both the peak stream power and the cumulative stream energy of individual hydrologic events. Bed load volumes scaled much more steeply with peak stream power and cumulative stream energy than tracer transport distances did, and bed load volumes scaled as roughly the third power of transport distances. These observations imply that large bed load transport events become large primarily by scouring the bed deeper and wider, and only secondarily by transporting the mobilized sediment farther. Using the sediment continuity equation, we can estimate the mean effective thickness of the actively transported layer, averaged over the entire channel width and the duration of individual flow events. This active layer thickness also followed approximate power law scaling with peak stream power and cumulative stream energy and ranged up to 0.57 m in the Erlenbach, broadly consistent with independent measurements.

Methane emissions from sugarcane vinasse storage and transportation systems: Comparison between open channels and tanks

Science.gov (United States)

Oliveira, Bruna Gonçalves; Carvalho, João Luís Nunes; Chagas, Mateus Ferreira; Cerri, Carlos Eduardo Pellegrino; Cerri, Carlos Clemente; Feigl, Brigitte Josefine

2017-06-01

Over the last few years the brazilian sugarcane sector has produced an average of 23.5 million liters of ethanol annually. This scale of production generates large amounts of vinasse, which depending on the manner that is disposed, can result significant greenhouse gas emissions. This study aimed to quantify the methane (CH4) emissions associated with the two most widespread systems of vinasse storage and transportation used in Brazil; open channel and those comprising of tanks and pipes. Additionally, a laboratory incubation study was performed with the aim of isolating the effects of vinasse, sediment and the interaction between these factors on CH4 emissions. We observed significant differences in CH4 emissions between the sampling points along the channels during both years of evaluation (2012-2013). In the channel system, around 80% of CH4 emissions were recorded from uncoated sections. Overall, the average CH4 emission intensity was 1.36 kg CO2eq m-3 of vinasse transported in open channels, which was 620 times higher than vinasse transported through a system of tanks and closed pipes. The laboratory incubation corroborated field results, suggesting that vinasse alone does not contribute significant emissions of CH4. Higher CH4 emissions were observed when vinasse and sediment were incubated together. In summary, our findings demonstrate that CH4 emissions originate through the anaerobic decomposition of organic material deposited on the bottom of channels and tanks. The adoption of coated channels as a substitute to uncoated channels offers the potential for an effective and affordable means of reducing CH4 emissions. Ultimately, the modernization of vinasse storage and transportation systems through the adoption of tank and closed pipe systems will provide an effective strategy for mitigating CH4 emissions generated during the disposal phase of the sugarcane ethanol production process.

Structure-function relation of phospholamban: modulation of channel activity as a potential regulator of SERCA activity.

Directory of Open Access Journals (Sweden)

Serena Smeazzetto

Full Text Available Phospholamban (PLN is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+-ATPase (SERCA in the sarcoplasmic reticulum. When reconstituted in planar lipid bilayers PLN exhibits ion channel activity with a low unitary conductance. From the effect of non-electrolyte polymers on this unitary conductance we estimate a narrow pore with a diameter of ca. 2.2 Å for this channel. This value is similar to that reported for the central pore in the structure of the PLN pentamer. Hence the PLN pentamer, which is in equilibrium with the monomer, is the most likely channel forming structure. Reconstituted PLN mutants, which either stabilize (K27A and R9C or destabilize (I47A the PLN pentamer and also phosphorylated PLN still generate the same unitary conductance of the wt/non-phosphorylated PLN. However the open probability of the phosphorylated PLN and of the R9C mutant is significantly lower than that of the respective wt/non-phosphorylated control. In the context of data on PLN/SERCA interaction and on Ca(2+ accumulation in the sarcoplasmic reticulum the present results are consistent with the view that PLN channel activity could participate in the balancing of charge during Ca(2+ uptake. A reduced total conductance of the K(+ transporting PLN by phosphorylation or by the R9C mutation may stimulate Ca(2+ uptake in the same way as an inhibition of K(+ channels in the SR membrane. The R9C-PLN mutation, a putative cause of dilated cardiomyopathy, might hence affect SERCA activity also via its inherent low open probability.

Chrometric properties of curvilinear beam transport channels with reverses of longitudinal magnetic field

International Nuclear Information System (INIS)

Kapchinskij, M.I.; Korenev, I.L.; Roginskij, L.A.

1990-01-01

Dynamics of charged particle beams in curvilinear transport channels comprising sections with counter direction of longitudinal focusing magnetic field is considered. It is shown that such magnetic field reverses reduce sufficiently the particle deflections conditioned by momentum spread of longitudinal motion and their application allows one to completely project the achromatic channel

Structure of the CLC-1 chloride channel from Homo sapiens.

Science.gov (United States)

Park, Eunyong; MacKinnon, Roderick

2018-05-29

CLC channels mediate passive Cl - conduction, while CLC transporters mediate active Cl - transport coupled to H + transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl - conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl - at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl - affinity distinguish CLC channels and transporters. © 2018, Park & MacKinnon.

Fast water transport in graphene nanofluidic channels

Science.gov (United States)

Xie, Quan; Alibakhshi, Mohammad Amin; Jiao, Shuping; Xu, Zhiping; Hempel, Marek; Kong, Jing; Park, Hyung Gyu; Duan, Chuanhua

2018-01-01

Superfast water transport discovered in graphitic nanoconduits, including carbon nanotubes and graphene nanochannels, implicates crucial applications in separation processes and energy conversion. Yet lack of complete understanding at the single-conduit level limits development of new carbon nanofluidic structures and devices with desired transport properties for practical applications. Here, we show that the hydraulic resistance and slippage of single graphene nanochannels can be accurately determined using capillary flow and a novel hybrid nanochannel design without estimating the capillary pressure. Our results reveal that the slip length of graphene in the graphene nanochannels is around 16 nm, albeit with a large variation from 0 to 200 nm regardless of the channel height. We corroborate this finding with molecular dynamics simulation results, which indicate that this wide distribution of the slip length is due to the surface charge of graphene as well as the interaction between graphene and its silica substrate.

Heat transport and surface heat transfer with helium in rotating channels

International Nuclear Information System (INIS)

Schnapper, C.

1978-06-01

Heat transport and surface heat transfer with helium in rotating radially arranged channels were experimentally studied with regard to cooling of large turbogenerators with superconducting windings. Measurements with thermosiphon and thermosiphon loops of different channel diameters were performed, and results are presented. The thermodynamic state of the helium in a rotating thermosiphon and the mass flow rate in a thermosiphon loop is characterized by formulas. Heat transport by directed convection in thermosiphon loops is found to be more efficient 12 cm internal convection in thermosiphons. Steady state is reached sooner in thermosiphon loops than in thermosiphons, when heat load suddenly changes. In a very large centrifugal field single-phase heat transfer with natural and forced convection is described by similar formulas which are also applicable 10 thermosiphons in gravitation field or to heat transfer to non-rotating helium. (orig.) [de

Sediment Transport Capacity and Channel Processes in a Humid Tropical Montane River - Rio Pacuare, Costa Rica

Science.gov (United States)

Lind, P.; McDowell, P. F.

2017-12-01

Investigating sediment transport capacity as well as the spatial and temporal variations of sediment flux are critical component of river research, especially for applications in resource management and conservation, hazards assessment and planning, and riverine ecology. The bedload fraction of sediment transported through montane rivers often defines channel and bed form processes. It is understood that humid tropical montane rivers are capable of producing some of the largest quantities of sediment per unit drainage area. Bedload flux reported on a few Southeast Asian humid tropical montane rivers show that bedload constituted 16-75% of the total sediment load - this is notably higher than the generally accepted 10% of a channel's sediment load. However, to date almost all of the research done on sediment transport in humid tropical systems has focused on suspended load. This study presents annual bedload transport rate estimates for six field sites distributed within 45 river kilometers (Rkm) of the montane portion of the Rio Pacuare, located in the Talamanca Mountains of Costa Rica. This research reveals that flows capable of mobilizing the D84 occur on average at least once but often multiple times a year in this river system. The Rio Pacuare has a sufficient supply of sediment to meet its high transport capacity needs. As a result, large active bars composed of imbricated boulders define channel form at moderate and low flows throughout the study area. Differences in the magnitude, as well as the spatial and temporal variations of sediment flux at each field site are discussed in relation to stream power, and annual/inter-annual precipitation patterns. A unique mix of field and remote sensing techniques were applied to address these questions and to overcome some of the challenges of tropical river research. For example, due to the large grain size and high stream energy, grain mobilization and validation of modeled shear stress requirements for transport

Numerical Simulation of Plume Transport in Channel Bend with Different Sediment Diameters

Science.gov (United States)

Kim, H. S.; Chen, H. C.

2017-12-01

The flow and transport of suspended sediment particles, in the form of plume, were simulated using an in-house Computational Fluid Dynamics (CFD) solver FANS3D (Finite Analytic Navier-Stokes code for 3D flow). The motivation for this investigation is to provide a means to simulate and visualize dispersal systems in a complex flow environment. The physical domain considered is a 90-degrees channel bend with wingwall abutments, which induces complex, three-dimensional flow characteristics. At the inlet of the channel, a sediment plume with the volumetric concentration of 1,000 parts per million (ppm) was constantly supplied. For simplicity, it was assumed that neither deposition nor erosion takes place inside the channel and settling sediment was made to pass through the bed surface. The effect of the sediment particle size was also analyzed using two different median diameters: 0.10 mm and 0.20 mm. It was shown that flow acceleration and vortices cause strong mixing inside the channel. The three-dimensional time series from the simulation captured increasing suspended sediment concentration downstream of the abutments, along the outer bank. When the median diameter was varied, the sediment concentration at certain locations differed by orders of magnitude, indicating that the settling velocity dominates the transport process for larger diameters.

Mechanisms of Sediment Transport to an Abandoned Distributary Channel on the Huanghe (Yellow River) Delta, China

Science.gov (United States)

Kumpf, L. L.; Kineke, G. C.; Carlson, B.; Mullane, M.

2017-12-01

Avulsions on the fine-grained Huanghe delta have left it scarred with traces of abandoned distributary channels that become intertidal systems, open to water and sediment exchange with the sea. In 1996, an engineered avulsion of the Huanghe left a 30 km long abandoned channel to the south of the modern active river channel. Though all fluvial input was cut off, present-day sedimentation on the new tidal flats has been observed at rates around 2 cm/yr. The source must be suspended-sediment from the Bohai Sea conveyed by the tidal channel network, but the mechanisms promoting sediment import are unknown. Possible mechanisms include (A) import sourced from the sediment-rich buoyant coastal plume, (B) wave resuspension on the shallow shelf, (C) reverse-estuarine residual circulation in the tidal channel, and (D) tidal asymmetry in the channel. Over three summers, in situ measurements of current velocity, suspended-sediment concentration (SSC), and wave climate were made on the delta front, and measurements of velocity, SSC, and salinity were made within the tidal channel. Results suggest that the buoyant plume from the active Huanghe channel can transport sediment south toward the tidal channel mouth (A). Additionally, wave resuspension (B) takes place on the subaqueous topset beds when the significant wave height exceeds 1 m, providing potential sources of suspended-sediment to the tidal channel. Within the abandoned channel, the tidal channel can become hypersaline and exhibit reverse-estuarine circulation (C), which would promote import of turbid coastal water near the surface. Time-series of velocity in the tidal channel indicate that ebb currents are consistently higher than flood currents through the spring-neap cycle (D), with maximum velocities exceeding 1 m/s and corresponding maximum SSC reaching 2 g/L during spring tide. While ebb dominance would typically tend to flush the system of its sediment over time, sediment supplied to the tidal flats may not be

Molecular and functional expression of high conductance Ca 2+ activated K+ channels in the eel intestinal epithelium

DEFF Research Database (Denmark)

Lionetto, Maria G; Rizzello, Antonia; Giordano, Maria E

2008-01-01

Several types of K(+) channels have been identified in epithelial cells. Among them high conductance Ca(2+)-activated K(+) channels (BK channels) are of relevant importance for their involvement in regulatory volume decrease (RVD) response following hypotonic stress. The aim of the present work...... was to investigate the functional and molecular expression of BK in the eel intestine, which is a useful experimental model for cell volume regulation research. In the present paper using rat BK channel-specific primer, a RT-PCR signal of 696 pb cDNA was detected in eel intestine, whole nucleotide sequence showed...... high similarity (83%) to the alpha subunit of BK channel family. BK channel protein expression was verified by immunoblotting and confocal microscopy, while the functional role of BK channels in epithelial ion transport mechanisms and cell volume regulation was examined by electrophysiological...

Active and passive transport of cargo in a corrugated channel: A lattice model study

Science.gov (United States)

Dey, Supravat; Ching, Kevin; Das, Moumita

2018-04-01

Inside cells, cargos such as vesicles and organelles are transported by molecular motors to their correct locations via active motion on cytoskeletal tracks and passive, Brownian diffusion. During the transportation of cargos, motor-cargo complexes (MCCs) navigate the confining and crowded environment of the cytoskeletal network and other macromolecules. Motivated by this, we study a minimal two-state model of motor-driven cargo transport in confinement and predict transport properties that can be tested in experiments. We assume that the motion of the MCC is directly affected by the entropic barrier due to confinement if it is in the passive, unbound state but not in the active, bound state where it moves with a constant bound velocity. We construct a lattice model based on a Fokker Planck description of the two-state system, study it using a kinetic Monte Carlo method and compare our numerical results with analytical expressions for a mean field limit. We find that the effect of confinement strongly depends on the bound velocity and the binding kinetics of the MCC. Confinement effectively reduces the effective diffusivity and average velocity, except when it results in an enhanced average binding rate and thereby leads to a larger average velocity than when unconfined.

Transport of bedload sediment and channel morphology of a southeast Alaska stream.

Science.gov (United States)

Margaret A. Estep; Robert L. Beschta

1985-01-01

During 1980-81, transport of bedload sediment and channel morphology were determined at Trap Bay Creek, a third-order stream that drains a 13.5-square kilometer watershed on Chichagof island in southeast Alaska. Bedload sediment was sampled for 10 storms: peak flows ranged from 0.6 to 19.0 cubic meters per second, and transport rates ranged from 4 to 4400 kilograms per...

Asymmetric ion transport through ion-channel-mimetic solid-state nanopores.

Science.gov (United States)

Guo, Wei; Tian, Ye; Jiang, Lei

2013-12-17

Both scientists and engineers are interested in the design and fabrication of synthetic nanofluidic architectures that mimic the gating functions of biological ion channels. The effort to build such structures requires interdisciplinary efforts at the intersection of chemistry, materials science, and nanotechnology. Biological ion channels and synthetic nanofluidic devices have some structural and chemical similarities, and therefore, they share some common features in regulating the traverse ionic flow. In the past decade, researchers have identified two asymmetric ion transport phenomena in synthetic nanofluidic structures, the rectified ionic current and the net diffusion current. The rectified ionic current is a diode-like current-voltage response that occurs when switching the voltage bias. This phenomenon indicates a preferential direction of transport in the nanofluidic system. The net diffusion current occurs as a direct product of charge selectivity and is generated from the asymmetric diffusion through charged nanofluidic channels. These new ion transport phenomena and the elaborate structures that occur in biology have inspired us to build functional nanofluidic devices for both fundamental research and practical applications. In this Account, we review our recent progress in the design and fabrication of biomimetic solid-state nanofluidic devices with asymmetric ion transport behavior. We demonstrate the origin of the rectified ionic current and the net diffusion current. We also identify several influential factors and discuss how to build these asymmetric features into nanofluidic systems by controlling (1) nanopore geometry, (2) surface charge distribution, (3) chemical composition, (4) channel wall wettability, (5) environmental pH, (6) electrolyte concentration gradient, and (7) ion mobility. In the case of the first four features, we build these asymmetric features directly into the nanofluidic structures. With the final three, we construct

Investigation of thermal energy transport from an anisotropic central heating element to the adjacent channels: A multipoint flux approximation

KAUST Repository

Salama, Amgad; Sun, Shuyu; El-Amin, Mohamed

2015-01-01

anisotropy of the heating element and/or the encompassing plates on thermal energy transport to the fluid passing through the two channels. When the medium is anisotropic with respect to thermal conductivity; energy transport to the neighboring channels

Temporal variability of mass transport across Canary Islands Channels

Science.gov (United States)

Marrero-Díaz, Ángeles; Rodríguez-Santana, Ángel; José Machín, Francisco; García-Weil, Luis; Sangrà, Pablo; Vélez-Belchí, Pedro; Fraile-Nuez, Eugenio

2014-05-01

The equatorward flowing Canary Current (CC) is the main feature of the circulation in the Canary Islands region. The CC flow perturbation by the Canary Islands originate the Canary Eddy Corridor which is the major pathway for long lived eddies in the subtropical North Atlantic (Sangrà et al., 2009, DSR). Therefore the variability of the CC passing through the Canary Archipelago will have both local and regional importance. Past studies on the CC variability trough the Canary Islands point out a clearly seasonal variability (Fraile-Nuez et al, 2010 (JGR); Hernández-Guerra et al, 2002 (DSR)). However those studies where focused on the eastern islands channels missing the variability through the western island channels which are the main source of long lived eddies. In order to fill this gap from November 2012 until September 2013 we conducted trimonthly surveys crossing the whole islands channels using opportunity ships (Naviera Armas Ferries). XBT and XCTD where launched along the cross channels transects. Additionally a closed box circling the Archipelago was performed on October 2013 as part of the cruise RAPROCAN-2013 (IEO) using also XBT and XCTD. Dynamical variables where derived inferring salinity from S(T,p) analytical relationships for the region updated with new XCTD data. High resolution, vertical sections of temperature, potential density, geostrophic velocity and transport where obtained. Our preliminary results suggest that the CC suffer a noticeable acceleration in those islands channels where eddy shedding is more frequent. They also indicate a clearly seasonal variability of the flows passing the islands channels. With this regard we observed significant differences on the obtained seasonal variability with respect the cited past studies on the eastern islands channel (Lanzarote / Fuerteventura - Africa coast). This work was co-funded by Canary Government (TRAMIC project: PROID20100092) and the European Union (FEDER).

Vulnerable transportation and utility assets near actively migrating streams in Indiana

Science.gov (United States)

Sperl, Benjamin J.

2017-11-02

An investigation was completed by the U.S. Geological Survey in cooperation with the Indiana Office of Community and Rural Affairs that found 1,132 transportation and utility assets in Indiana are vulnerable to fluvial erosion hazards due to close proximity to actively migrating streams. Locations of transportation assets (bridges, roadways, and railroad lines) and selected utility assets (high-capacity overhead power-transmission lines, underground pipelines, water treatment facilities, and in-channel dams) were determined using aerial imagery hosted by the Google Earth platform. Identified assets were aggregated by stream reach, county, and class. Accompanying the report is a polyline shapefile of the stream reaches documented by Robinson. The shapefile, derived from line work in the National Hydrography Dataset and attributed with channel migration rates, is released with complete Federal Geographic Data Committee metadata. The data presented in this report are intended to help stakeholders and others identify high-risk areas where transportation and utility assets may be threatened by fluvial erosion hazards thus warranting consideration for mitigation strategies.

Liquid Water Transport in the Reactant Channels of Proton Exchange Membrane Fuel Cells

Science.gov (United States)

Banerjee, Rupak

Water management has been identified as a critical issue in the development of PEM fuel cells for automotive applications. Water is present inside the PEM fuel cell in three phases, i.e. liquid phase, vapor phase and mist phase. Liquid water in the reactant channels causes flooding of the cell and blocks the transport of reactants to the reaction sites at the catalyst layer. Understanding the behavior of liquid water in the reactant channels would allow us to devise improved strategies for removing liquid water from the reactant channels. In situ fuel cell tests have been performed to identify and diagnose operating conditions which result in the flooding of the fuel cell. A relationship has been identified between the liquid water present in the reactant channels and the cell performance. A novel diagnostic technique has been established which utilizes the pressure drop multiplier in the reactant channels to predict the flooding of the cell or the drying-out of the membrane. An ex-situ study has been undertaken to quantify the liquid water present in the reactant channels. A new parameter, the Area Coverage Ratio (ACR), has been defined to identify the interfacial area of the reactant channel which is blocked for reactant transport by the presence of liquid water. A parametric study has been conducted to study the effect of changing temperature and the inlet relative humidity on the ACR. The ACR decreases with increase in current density as the gas flow rates increase, removing water more efficiently. With increase in temperature, the ACR decreases rapidly, such that by 60°C, there is no significant ACR to be reported. Inlet relative humidity of the gases does change the saturation of the gases in the channel, but did not show any significant effect on the ACR. Automotive powertrains, which is the target for this work, are continuously faced with transient changes. Water management under transient operating conditions is significantly more challenging and has not

CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease.

Science.gov (United States)

Jentsch, Thomas J; Pusch, Michael

2018-07-01

CLC anion transporters are found in all phyla and form a gene family of eight members in mammals. Two CLC proteins, each of which completely contains an ion translocation parthway, assemble to homo- or heteromeric dimers that sometimes require accessory β-subunits for function. CLC proteins come in two flavors: anion channels and anion/proton exchangers. Structures of these two CLC protein classes are surprisingly similar. Extensive structure-function analysis identified residues involved in ion permeation, anion-proton coupling and gating and led to attractive biophysical models. In mammals, ClC-1, -2, -Ka/-Kb are plasma membrane Cl - channels, whereas ClC-3 through ClC-7 are 2Cl - /H + -exchangers in endolysosomal membranes. Biological roles of CLCs were mostly studied in mammals, but also in plants and model organisms like yeast and Caenorhabditis elegans. CLC Cl - channels have roles in the control of electrical excitability, extra- and intracellular ion homeostasis, and transepithelial transport, whereas anion/proton exchangers influence vesicular ion composition and impinge on endocytosis and lysosomal function. The surprisingly diverse roles of CLCs are highlighted by human and mouse disorders elicited by mutations in their genes. These pathologies include neurodegeneration, leukodystrophy, mental retardation, deafness, blindness, myotonia, hyperaldosteronism, renal salt loss, proteinuria, kidney stones, male infertility, and osteopetrosis. In this review, emphasis is laid on biophysical structure-function analysis and on the cell biological and organismal roles of mammalian CLCs and their role in disease.

Theoretical analysis of selectivity mechanisms in molecular transport through channels and nanopores

International Nuclear Information System (INIS)

Agah, Shaghayegh; Pasquali, Matteo; Kolomeisky, Anatoly B.

2015-01-01

Selectivity is one of the most fundamental concepts in natural sciences, and it is also critically important in various technological, industrial, and medical applications. Although there are many experimental methods that allow to separate molecules, frequently they are expensive and not efficient. Recently, a new method of separation of chemical mixtures based on utilization of channels and nanopores has been proposed and successfully tested in several systems. However, mechanisms of selectivity in the molecular transport during the translocation are still not well understood. Here, we develop a simple theoretical approach to explain the origin of selectivity in molecular fluxes through channels. Our method utilizes discrete-state stochastic models that take into account all relevant chemical transitions and can be solved analytically. More specifically, we analyze channels with one and two binding sites employed for separating mixtures of two types of molecules. The effects of the symmetry and the strength of the molecular-pore interactions are examined. It is found that for one-site binding channels, the differences in the strength of interactions for two species drive the separation. At the same time, in more realistic two-site systems, the symmetry of interaction potential becomes also important. The most efficient separation is predicted when the specific binding site is located near the entrance to the nanopore. In addition, the selectivity is higher for large entrance rates into the channel. It is also found that the molecular transport is more selective for repulsive interactions than for attractive interactions. The physical-chemical origin of the observed phenomena is discussed

Plant ion channels: gene families, physiology, and functional genomics analyses.

Science.gov (United States)

Ward, John M; Mäser, Pascal; Schroeder, Julian I

2009-01-01

Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

Maintenance of an obstruction-forced pool in a gravel-bed channel: streamflow, channel morphology, and sediment transport.

Science.gov (United States)

Richard D. Woodsmith; Marwan A. Hassan

2005-01-01

Maintenance of pool morphology in a stream channel with a mobile bed requires hydraulic conditions at moderate to high flows that route bed load through the pool as it is delivered from upstream. Through field measurements of discharge, vertical velocity profiles, bed load transport, and streambed scour, fill, and grain-size distribution, we found that maintenance of a...

Cell swelling activates K⁺ and Cl^- channels as well as nonselective, stretch-activated cation channels in ehrlich ascites tumor cells

DEFF Research Database (Denmark)

Christensen, Ove; Hoffmann, Else Kay

1992-01-01

Cell-attached patch-clamp recordings from Ehrlich ascites tumor cells reveal nonselective cation channels which are activated by mechanical deformation of the membrane. These channels are seen when suction is applied to the patch pipette or after osmotic cell swelling. The channel activation does...... system. In isolated insideout patches a Ca2+-dependent, inwardly rectifying K+ channel is demonstrated. The single-channel conductance recorded with symmetrical 150 mm K+ solutions is for inward current estimated at 40 pS and for outward current at 15 pS. Activation of the K+ channel takes place after...... by membrane stretch (suction). The time-averaged number of open K+ channels during regulatory volume decrease (RVD) can be estimated at 40 per cell. The number of open K+ channels following addition of Ca2+ plus ionophore A23187 was estimated at 250 per cell. Concurrent activation in cell-attached patches...

Characterization of active ion transport across primary rabbit corneal epithelial cell layers (RCrECL) cultured at an air-interface.

Science.gov (United States)

Chang-Lin, Joan-En; Kim, Kwang-Jin; Lee, Vincent H L

2005-06-01

Previously, we reported the development of a primary culture model of tight rabbit corneal epithelial cell layers (RCrECL) characterizing bioelectric parameters, morphology, cytokeratin, and passive permeability. In the present study, we specifically evaluated the active ion transport processes of RCrECL cultured from either pigmented or albino rabbits. Primary cultured RCrECL were grown at an air-interface on Clear-Snapwells precoated with collagen/fibronectin/laminin and mounted in a modified Ussing-type chamber for the evaluation of their active ion transport processes under short-circuited conditions. Contribution of active Na(+) and Cl(-) transport to overall short-circuit current (I(sc)) was evaluated by removing Na(+) and Cl(-), respectively, from bathing fluids of RCrECL and measurements of net fluxes of Na(+) and Cl(-) using (22)Na and (36)Cl, respectively. Amiloride and benzamil were used to determine the role of apical Na(+)-channel activities to net Na(+) fluxes. N-phenylanthranilic acid (NPAA), ouabain, BaCl(2) and bumetanide were used to determine the role of basolateral Na,K-ATPase, apical Cl(-)-channel, and basolateral K(+)-channel and Na(+)(K(+))2Cl(-)-cotransporter activities, respectively, in active ion transport across RCrECL. I(sc) of RCrECL derived from pigmented rabbits was comprised of 64+/-2% and 44+/-5% for active Na(+) and Cl(-) transport, respectively, consistent with net Na(+) absorption and Cl(-) secretion of 0.062+/-0.006 and 0.046+/-0.008 muEq/cm(2)/hr estimated from radionuclide fluxes. Apical amiloride and benzamil inhibited I(sc) by up to approximately 50% with an IC(50) of 1 and 0.1 microm, respectively, consistent with participation of apical epithelial Na(+)-channels to net Na(+) absorption across RCrECL cultured from pigmented rabbits. Addition of ouabain to the basolateral, NPAA to the apical, BaCl(2) to the basolateral and bumetanide to basolateral fluid decreased I(sc) by 86+/-1.5%, 53+/-3%, 18+/-1.8% and 13+/-1.9% in RCr

Mass and charge transport in micro and nanofluidic channels

DEFF Research Database (Denmark)

Mortensen, Niels Asger; Olesen, Laurits Højgaard; Okkels, Fridolin

2007-01-01

and charge transport coefficients that satisfy Onsager relations. In the limit of nonoverlapping Debye layers the transport coefficients are simply expressed in terms of parameters of the electrolyte as well as the hydraulic radiusR ¼ 2A=P with Aand P being the cross-sectional area and perimeter......, respectively. In particular, we consider the limits of thin nonoverlapping as well as strongly overlapping Debye layers, respectively, and calculate the corrections to the hydraulic resistance due to electrohydrodynamic interactions.......We consider laminar flow of incompressible electrolytes in long, straight channels driven by pressure and electroosmosis. We use aHilbert space eigenfunction expansion to address the general problem of an arbitrary cross section and obtain general results in linear-response theory for the mass...

Lipid nanocapsules containing the non-ionic surfactant Solutol HS15 inhibit the transport of calcium through hyperforin-activated channels in neuronal cells.

Science.gov (United States)

Chauvet, Sylvain; Barras, Alexandre; Boukherroub, Rabah; Bouron, Alexandre

2015-12-01

Hyperforin is described as a natural antidepressant inhibiting the reuptake of neurotransmitters and also activating cation channels. However the blood-brain barrier limits the access to the brain of this biomolecule. To circumvent this problem it was envisaged to encapsulate hyperforin into biomimetic lipid nano-carriers like lipid nanocapsules (LNCs). When testing the safety of 25 nm LNCs it appeared that they strongly blocked hyperforin-activated Ca2+ channels of cultured cortical neurons. This inhibition was due to one of their main component: solutol HS15 (polyoxyethylene-660-12-hydroxy stearate), a non-ionic soluble surfactant. Solutol HS15 rapidly depresses in a concentration-dependent manner the entry of Ca2+ through hyperforin-activated channels without influencing store-operated channels. This effect is mimicked by Brij58 but not by PEG600, indicating that the lipid chain of Solutol HS15 is important in determining its effects on the channels. The inhibition of the Ca2+ fluxes depends on the cellular cholesterol content; it is stronger after depleting cholesterol with methyl-β-cyclodextrin and is nearly absent on cells cultured in a cholesterol-rich medium. When chronically applied for 24 h, Solutol HS15 slightly up-regulates the entry of Ca2+ through hyperforin-activated channels. Similar observations were made when testing 25 nm lipid nanocapsules containing the surfactant Solutol HS15. Altogether, this study shows that Solutol HS15 perturbs in a cholesterol-dependent manner the activity of some neuronal channels. This is the first demonstration that LNCs containing this surfactant can influence cellular calcium signaling in the brain, a finding that can have important clinical implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fluctuation theorem for channel-facilitated membrane transport of interacting and noninteracting solutes.

Science.gov (United States)

Berezhkovskii, Alexander M; Bezrukov, Sergey M

2008-05-15

In this paper, we discuss the fluctuation theorem for channel-facilitated transport of solutes through a membrane separating two reservoirs. The transport is characterized by the probability, P(n)(t), that n solute particles have been transported from one reservoir to the other in time t. The fluctuation theorem establishes a relation between P(n)(t) and P-(n)(t): The ratio P(n)(t)/P-(n)(t) is independent of time and equal to exp(nbetaA), where betaA is the affinity measured in the thermal energy units. We show that the same fluctuation theorem is true for both single- and multichannel transport of noninteracting particles and particles which strongly repel each other.

First demonstration of single-mode MCF transport network with crosstalk-aware in-service optical channel control

DEFF Research Database (Denmark)

Pulverer, K.; Tanaka, T.; Häbel, U.

2017-01-01

We demonstrate the first crosstalk-aware traffic engineering as a use case in a multicore fibre transport network. With the help of a software-defined network controller, modulation format and channel route are adaptively changed using programmable devices with XT monitors.......We demonstrate the first crosstalk-aware traffic engineering as a use case in a multicore fibre transport network. With the help of a software-defined network controller, modulation format and channel route are adaptively changed using programmable devices with XT monitors....

Entropic transport without external force in confined channel with oscillatory boundary

Energy Technology Data Exchange (ETDEWEB)

Ding, Huai; Jiang, Huijun; Hou, Zhonghuai, E-mail: hzhlj@ustc.edu.cn [Department of Chemical Physics & Hefei National Laboratory for Physical Sciences at Microscales, University of Science and Technology of China, Hefei, Anhui 230026 (China)

2015-12-28

The dynamics of point-like Brownian particles in a periodic confined channel with oscillating boundaries has been studied. Directional transport (DT) behavior, characterized by net displacement along the horizontal direction, is observed even without external force which is necessary for the conventional DT where the boundaries are static. For typical parameter values, the average velocity V{sub t} of DT reaches a maximum with the variation of the noise intensity D, being alike to the phenomenon of stochastic resonance. Interestingly, we find that V{sub t} shows nontrivial dependences on the particle gravity G depending on the noise level. When the noise is large, V{sub t} increases monotonically with G indicating that heavier particle moves faster, while for small noise, V{sub t} shows a bell-shape dependence on G, suggesting that a particle with an intermediate weight may move the fastest. Such results were not observed for DT in a channel with static boundaries. To understand these findings, we have adopted an effective one-dimensional coarsening description, which facilitates us to introduce an effective entropic force along the horizontal direction. The average force is apparently nonzero due to the oscillatory boundary, hence leading to the net transport, and it shows similar dependences as V{sub t} on the noise intensity D and particle gravity G. The dependences of the DT behavior on other parameters describing the oscillatory channel have also been investigated, showing that DT is more pronounced for larger oscillation amplitude and frequency, and asymmetric geometry within a channel period and phase difference between neighboring periods are both necessary for the occurrence of DT.

Large conductance Ca2+-activated K+ (BK channel: Activation by Ca2+ and voltage

Directory of Open Access Journals (Sweden)

RAMÓN LATORRE

2006-01-01

Full Text Available Large conductance Ca2+-activated K+ (BK channels belong to the S4 superfamily of K+ channels that include voltage-dependent K+ (Kv channels characterized by having six (S1-S6 transmembrane domains and a positively charged S4 domain. As Kv channels, BK channels contain a S4 domain, but they have an extra (S0 transmembrane domain that leads to an external NH2-terminus. The BK channel is activated by internal Ca2+, and using chimeric channels and mutagenesis, three distinct Ca2+-dependent regulatory mechanisms with different divalent cation selectivity have been identified in its large COOH-terminus. Two of these putative Ca2+-binding domains activate the BK channel when cytoplasmic Ca2+ reaches micromolar concentrations, and a low Ca2+ affinity mechanism may be involved in the physiological regulation by Mg2+. The presence in the BK channel of multiple Ca2+-binding sites explains the huge Ca2+ concentration range (0.1 μM-100 μM in which the divalent cation influences channel gating. BK channels are also voltage-dependent, and all the experimental evidence points toward the S4 domain as the domain in charge of sensing the voltage. Calcium can open BK channels when all the voltage sensors are in their resting configuration, and voltage is able to activate channels in the complete absence of Ca2+. Therefore, Ca2+ and voltage act independently to enhance channel opening, and this behavior can be explained using a two-tiered allosteric gating mechanism.

Sausage instability in a proton-beam transport through wall-confined plasma channel

International Nuclear Information System (INIS)

Yamada, Tetsuo; Masugata, Katsumi; Matsui, Masao; Yatsui, Kiyoshi

1983-01-01

An instability observed previously in a 800-keV of proton-beam transport through a wall-confined, z-discharged plasma channel (1-m long) has been identified as a sausage type from measurements made using an image converter campera. Clear evidence of the sausage instability has been obtained from the streak and framing photographs. When the instability grows with time, the wavelength tends to increase. The pinch velocity of the channel has also been measured in a parameter space, which gives reasonable agreement with the existing theory. (author)

Effect of stochastic gating on channel-facilitated transport of non-interacting and strongly repelling solutes

Science.gov (United States)

Berezhkovskii, Alexander M.; Bezrukov, Sergey M.

2017-08-01

Ligand- or voltage-driven stochastic gating—the structural rearrangements by which the channel switches between its open and closed states—is a fundamental property of biological membrane channels. Gating underlies the channel's ability to respond to different stimuli and, therefore, to be functionally regulated by the changing environment. The accepted understanding of the gating effect on the solute flux through the channel is that the mean flux is the product of the flux through the open channel and the probability of finding the channel in the open state. Here, using a diffusion model of channel-facilitated transport, we show that this is true only when the gating is much slower than the dynamics of solute translocation through the channel. If this condition breaks, the mean flux could differ from this simple estimate by orders of magnitude.

Molecular Aspects of Structure, Gating, and Physiology of pH-Sensitive Background K2P and Kir K+-Transport Channels

Science.gov (United States)

Sepúlveda, Francisco V.; Pablo Cid, L.; Teulon, Jacques; Niemeyer, María Isabel

2015-01-01

K+ channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K+ channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K+ homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K+-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge. PMID:25540142

Kinetics of proton transport into influenza virions by the viral M2 channel.

Directory of Open Access Journals (Sweden)

Tijana Ivanovic

Full Text Available M2 protein of influenza A viruses is a tetrameric transmembrane proton channel, which has essential functions both early and late in the virus infectious cycle. Previous studies of proton transport by M2 have been limited to measurements outside the context of the virus particle. We have developed an in vitro fluorescence-based assay to monitor internal acidification of individual virions triggered to undergo membrane fusion. We show that rimantadine, an inhibitor of M2 proton conductance, blocks the acidification-dependent dissipation of fluorescence from a pH-sensitive virus-content probe. Fusion-pore formation usually follows internal acidification but does not require it. The rate of internal virion acidification increases with external proton concentration and saturates with a pK(m of ∼4.7. The rate of proton transport through a single, fully protonated M2 channel is approximately 100 to 400 protons per second. The saturating proton-concentration dependence and the low rate of internal virion acidification derived from authentic virions support a transporter model for the mechanism of proton transfer.

Role of endolymphatic anion transport in forskolin-induced Cl- activity increase of scala media.

Science.gov (United States)

Kitano, I; Mori, N; Matsunaga, T

1995-03-01

To determine the role of anion transport in the forskolin-induced Cl- increase of scala media (SM), effects of forskolin on the EP (endocochlear potential) and Cl- activity (ACl) in SM were examined with double-barrelled Cl(-)-selective microelectrodes. The experiments were carried out on guinea pig cochleae, using a few anion transport inhibitors: IAA-94 for a Cl- channel blocker, bumetanide (BU) for an Na+/K+/2Cl- cotransport blocker, and SITS and DIDS for Cl-/HCO3- exchange blockers. The application of forskolin (200 microM) into scala vestibuli (SV) caused a 20 mEq increase of endolymphatic ACl and a 15 mV elevation of EP, and IAA-94 with forskolin completely abolished these responses. Although each application of BU, SITS or DIDS did not completely suppress EP elevation, the concurrent application of these inhibitors completely suppressed EP with endolymphatic ACl increase. The results indicate the involvement of Cl- channels, Na+/K+/2Cl- cotransport and Cl-/HCO3- exchange in forskolin-induced increase of ACl and EP. The role of adenylate cyclase activation and Cl- transport in endolymph homeostasis was discussed.

Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643)

DEFF Research Database (Denmark)

Hansen, Rie Schultz; Diness, Thomas Goldin; Christ, Torsten

2005-01-01

The cardiac action potential is generated by a concerted action of different ion channels and transporters. Dysfunction of any of these membrane proteins can give rise to cardiac arrhythmias, which is particularly true for the repolarizing potassium channels. We suggest that an increased repolari......The cardiac action potential is generated by a concerted action of different ion channels and transporters. Dysfunction of any of these membrane proteins can give rise to cardiac arrhythmias, which is particularly true for the repolarizing potassium channels. We suggest that an increased......M. Application of NS1643 also resulted in a prolonged postrepolarization refractory time. Finally, cardiomyocytes exposed to NS1643 resisted reactivation by small depolarizing currents mimicking early afterdepolarizations. In conclusion, HERG channel activation by small molecules such as NS1643 increases...

The effect of a concentration-dependent viscosity on particle transport in a channel flow with porous walls

KAUST Repository

Herterich, James G.; Griffiths, Ian M.; Vella, Dominic; Field, Robert W.

2014-01-01

The transport of a dilute suspension of particles through a channel with porous walls, accounting for the concentration dependence of the viscosity, is analyzed. In particular, we study two cases of fluid permeation through the porous channel walls

Incision of the Jezero Crater Outflow Channel by Fluvial Sediment Transport

Science.gov (United States)

Holo, S.; Kite, E. S.

2017-12-01

Jezero crater, the top candidate landing site for the Mars 2020 rover, once possessed a lake that over-spilled and eroded a large outflow channel into the Eastern rim. The Western deltaic sediments that would be the primary science target of the rover record a history of lake level, which is modulated by the inflow and outflow channels. While formative discharges for the Western delta exist ( 500 m3/s), little work has been done to see if these flows are the same responsible for outflow channel incision. Other models of the Jezero outflow channel incision assume that a single rapid flood (incision timescales of weeks), with unknown initial hydraulic head and no discharge into the lake (e.g. from the inflow channels or the subsurface), incised an open channel with discharge modulated by flow over a weir. We present an alternate model where, due to an instability at the threshold of sediment motion, the incision of the outflow channel occurs in concert with lake filling. In particular, we assume a simplified lake-channel-valley system geometry and that the channel is hydraulically connected to the filling/draining crater lake. Bed load sediment transport and water discharge through the channel are quantified using the Meyer-Peter and Mueller relation and Manning's law respectively. Mass is conserved for both water and sediment as the lake level rises/falls and the channel incises. This model does not resolve backwater effects or concavity in the alluvial system, but it does capture the non-linear feedbacks between lake draining, erosion rate, channel flow rate, and slope relaxation. We identify controls on incision of the outflow channel and estimate the time scale of outflow channel formation through a simple dynamical model. We find that the observed 300m of channel erosion can be reproduced in decades to centuries of progressive bed load as the delta forming flows fill the lake. This corresponds to time scales on the order of or smaller than the time scale

The Structure and Transport of Water and Hydrated Ions Within Hydrophobic, Nanoscale Channels

International Nuclear Information System (INIS)

Holt, J.K.; Herberg, J.L.; Wu, Y.; Schwegler, E.; Mehta, A.

2009-01-01

The purpose of this project includes an experimental and modeling investigation into water and hydrated ion structure and transport at nanomaterials interfaces. This is a topic relevant to understanding the function of many biological systems such as aquaporins that efficiently shuttle water and ion channels that permit selective transport of specific ions across cell membranes. Carbon nanotubes (CNT) are model nanoscale, hydrophobic channels that can be functionalized, making them artificial analogs for these biological channels. This project investigates the microscopic properties of water such as water density distributions and dynamics within CNTs using Nuclear Magnetic Resonance (NMR) and the structure of hydrated ions at CNT interfaces via X-ray Absorption Spectroscopy (XAS). Another component of this work is molecular simulation, which can predict experimental measurables such as the proton relaxation times, chemical shifts, and can compute the electronic structure of CNTs. Some of the fundamental questions this work is addressing are: (1) what is the length scale below which nanoscale effects such as molecular ordering become important, (2) is there a relationship between molecular ordering and transport?, and (3) how do ions interact with CNT interfaces? These are questions of interest to the scientific community, but they also impact the future generation of sensors, filters, and other devices that operate on the nanometer length scale. To enable some of the proposed applications of CNTs as ion filtration media and electrolytic supercapacitors, a detailed knowledge of water and ion structure at CNT interfaces is critical.

Chloride transport in human fibroblasts is activated by hypotonic shock

Energy Technology Data Exchange (ETDEWEB)

Rugolo, M.; Mastocola, T.; Flamigni, A.; Lenaz, G. (Universita' di Bologna (Italy))

1989-05-15

Incubation of human skin fibroblasts in hypotonic media induced the activation of {sup 36}Cl- efflux which was roughly proportional to the decrease in the osmolality of the media. The efflux of {sup 36}Cl- was insensitive to DIDS plus furosemide and inhibited by addition of a Cl- channel blocker such as 5-nitro-2-(3-phenyl propylamino) benzoic acid (NPPB). We propose that a conductive pathway for Cl- transport, almost silent in isotonic conditions, is activated by exposing human fibroblasts to hypotonic shock, this conclusion being supported by evidence that also {sup 36}Cl- influx was enhanced by hypotonic medium.

Effects of Drawdown and Structures on Bed-Load Transport in Pool 8 Navigation Channel

National Research Council Canada - National Science Library

Abraham, David; Hendrickson, Jon

2003-01-01

... of a pool drawdown and structures on bed-load transport in the Pool 8 navigation channel. Work was conducted as part of the Monitoring of Completed Navigation Projects (MCNP) program. BACKGROUND...

Interannual Variations of Surface Currents and Transports in the Sicily Channel Derived From Coastal Altimetry

Science.gov (United States)

Jebri, Fatma; Zakardjian, Bruno; Birol, Florence; Bouffard, Jérôme; Jullion, Loïc.; Sammari, Cherif

2017-11-01

A 20 year coastal altimetry data set (X-TRACK) is used, for the first time, to gain insight into the long-term interannual variations of the surface circulation in the Sicily Channel. First, a spectral along with a time/space diagram analysis are applied to the monthly means. They reveal a regionally coherent current patterns from track to track with a marked interannual variability that is unequally shared between the Atlantic Tunisian Current and Atlantic Ionian Stream inflows in the Sicily Channel and the Bifurcation Tyrrhenian Current outflow northeast of Sicily. Second, an empirical altimetry-based transport-like technique is proposed to quantify volume budgets inside the closed boxes formed by the crossing of the altimetry tracks and coastlines over the study area. A set of hydrographic measurements is used to validate the method. The inferred altimetry transports give a well-balanced mean eastward Atlantic Waters baroclinic flow of 0.4 Sv and standard deviations of 0.2 Sv on a yearly basis throughout the Sicily Channel and toward the Ionian Sea, which is fairly coherent with those found in the literature. Furthermore, the analysis allows to quantify the intrusions of Atlantic Waters over the Tunisian Shelf (0.12 ± 0.1 Sv) and highlights two main modes of variability of the main surface waters path over the Sicily Channel through the Bifurcation Atlantic Tunisian Current and Atlantic Ionian Stream systems. Some physical mechanisms are finally discussed with regards to changes in the observed currents and transports.

Parallel Evolution of Sperm Hyper-Activation Ca2+ Channels.

Science.gov (United States)

Cooper, Jacob C; Phadnis, Nitin

2017-07-01

Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca2+ into the sperm flagellum via CatSper ion channels. Surprisingly, all nine CatSper genes have been independently lost in several animal lineages. In Drosophila, sperm hyper-activation is performed through the cooption of the polycystic kidney disease 2 (pkd2) Ca2+ channel. The parallels between CatSpers in primates and pkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by > 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila. Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Expression, purification and functional reconstitution of slack sodium-activated potassium channels.

Science.gov (United States)

Yan, Yangyang; Yang, Youshan; Bian, Shumin; Sigworth, Fred J

2012-11-01

The slack (slo2.2) gene codes for a potassium-channel α-subunit of the 6TM voltage-gated channel family. Expression of slack results in Na(+)-activated potassium channel activity in various cell types. We describe the purification and reconstitution of Slack protein and show that the Slack α-subunit alone is sufficient for potassium channel activity activated by sodium ions as assayed in planar bilayer membranes and in membrane vesicles.

TRPP2 and TRPV4 form an EGF-activated calcium permeable channel at the apical membrane of renal collecting duct cells.

Directory of Open Access Journals (Sweden)

Zhi-Ren Zhang

Full Text Available Regulation of apical calcium entry is important for the function of principal cells of the collecting duct. However, the molecular identity and the regulators of the transporter/channel, which is responsible for apical calcium entry and what factors regulate the calcium conduction remain unclear.We report that endogenous TRPP2 and TRPV4 assemble to form a 23-pS divalent cation-permeable non-selective ion channel at the apical membrane of renal principal cells of the collecting duct. TRPP2\\TRPV4 channel complex was identified by patch-clamp, immunofluorescence and co-immunprecipitation studies in both principal cells that either possess normal cilia (cilia (+ or in which cilia are absent (cilia (-. This channel has distinct biophysical and pharmacological and regulatory profiles compared to either TRPP2 or TRPV4 channels. The rate of occurrence detected by patch clamp was higher in cilia (- compared to cilia (+ cells. In addition, shRNA knockdown of TRPP2 increased the prevalence of TRPV4 channel activity while knockdown of TRPV4 resulted in TRPP2 activity and knockdown of both proteins vastly decreased the 23-pS channel activity. Epidermal growth factor (EGF stimulated TRPP2\\TRPV4 channel through the EGF receptor (EGFR tyrosine kinase-dependent signaling. With loss of cilia, apical EGF treatment resulted in 64-fold increase in channel activity in cilia (- but not cilia (+ cells. In addition EGF increased cell proliferation in cilia (- cell that was dependent upon TRPP2\\TRPV4 channel mediated increase in intracellular calcium.We conclude that in the absence of cilia, an EGF activated TRPP2\\TRPV4 channel may play an important role in increased cell proliferation and cystogenesis.

Activation of purified calcium channels by stoichiometric protein phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Nunoki, K.; Florio, V.; Catterall, W.A. (Univ. of Washington, Seattle (USA))

1989-09-01

Purified dihydropyridine-sensitive calcium channels from rabbit skeletal muscle were reconstituted into phosphatidylcholine vesicles to evaluate the effect of phosphorylation by cyclic AMP-dependent protein kinase (PK-A) on their function. Both the rate and extent of {sup 45}Ca{sup 2+} uptake into vesicles containing reconstituted calcium channels were increased severalfold after incubation with ATP and PK-A. The degree of stimulation of {sup 45}Ca{sup 2+} uptake was linearly proportional to the extent of phosphorylation of the alpha 1 and beta subunits of the calcium channel up to a stoichiometry of approximately 1 mol of phosphate incorporated into each subunit. The calcium channels activated by phosphorylation were determined to be incorporated into the reconstituted vesicles in the inside-out orientation and were completely inhibited by low concentrations of dihydropyridines, phenylalkylamines, Cd{sup 2+}, Ni{sup 2+}, and Mg{sup 2+}. The results demonstrate a direct relationship between PK-A-catalyzed phosphorylation of the alpha 1 and beta subunits of the purified calcium channel and activation of the ion conductance activity of the dihydropyridine-sensitive calcium channels.

Activation of purified calcium channels by stoichiometric protein phosphorylation

International Nuclear Information System (INIS)

Nunoki, K.; Florio, V.; Catterall, W.A.

1989-01-01

Purified dihydropyridine-sensitive calcium channels from rabbit skeletal muscle were reconstituted into phosphatidylcholine vesicles to evaluate the effect of phosphorylation by cyclic AMP-dependent protein kinase (PK-A) on their function. Both the rate and extent of 45 Ca 2+ uptake into vesicles containing reconstituted calcium channels were increased severalfold after incubation with ATP and PK-A. The degree of stimulation of 45 Ca 2+ uptake was linearly proportional to the extent of phosphorylation of the alpha 1 and beta subunits of the calcium channel up to a stoichiometry of approximately 1 mol of phosphate incorporated into each subunit. The calcium channels activated by phosphorylation were determined to be incorporated into the reconstituted vesicles in the inside-out orientation and were completely inhibited by low concentrations of dihydropyridines, phenylalkylamines, Cd 2+ , Ni 2+ , and Mg 2+ . The results demonstrate a direct relationship between PK-A-catalyzed phosphorylation of the alpha 1 and beta subunits of the purified calcium channel and activation of the ion conductance activity of the dihydropyridine-sensitive calcium channels

The Arabidopsis vacuolar malate channel is a member of the ALMT family.

Science.gov (United States)

Kovermann, Peter; Meyer, Stefan; Hörtensteiner, Stefan; Picco, Cristiana; Scholz-Starke, Joachim; Ravera, Silvia; Lee, Youngsook; Martinoia, Enrico

2007-12-01

In plants, malate is a central metabolite and fulfills a large number of functions. Vacuolar malate may reach very high concentrations and fluctuate rapidly, whereas cytosolic malate is kept at a constant level allowing optimal metabolism. Recently, a vacuolar malate transporter (Arabidopsis thaliana tonoplast dicarboxylate transporter, AttDT) was identified that did not correspond to the well-characterized vacuolar malate channel. We therefore hypothesized that a member of the aluminum-activated malate transporter (ALMT) gene family could code for a vacuolar malate channel. Using GFP fusion constructs, we could show that AtALMT9 (A. thaliana ALMT9) is targeted to the vacuole. Promoter-GUS fusion constructs demonstrated that this gene is expressed in all organs, but is cell-type specific as GUS activity in leaves was detected nearly exclusively in mesophyll cells. Patch-clamp analysis of an Atalmt9 T-DNA insertion mutant exhibited strongly reduced vacuolar malate channel activity. In order to functionally characterize AtALMT9 as a malate channel, we heterologously expressed this gene in tobacco and in oocytes. Overexpression of AtALMT9-GFP in Nicotiana benthamiana leaves strongly enhanced the malate current densities across the mesophyll tonoplasts. Functional expression of AtALMT9 in Xenopus oocytes induced anion currents, which were clearly distinguishable from endogenous oocyte currents. Our results demonstrate that AtALMT9 is a vacuolar malate channel. Deletion mutants for AtALMT9 exhibit only slightly reduced malate content in mesophyll protoplasts and no visible phenotype, indicating that AttDT and the residual malate channel activity are sufficient to sustain the transport activity necessary to regulate the cytosolic malate homeostasis.

Quantum ballistic transport by interacting two-electron states in quasi-one-dimensional channels

Energy Technology Data Exchange (ETDEWEB)

Huang, Danhong [Air Force Research Laboratory, Space Vehicles Directorate, Kirtland Air Force Base, New Mexico 87117 (United States); Center for High Technology Materials, University of New Mexico, 1313 Goddard St SE, Albuquerque, New Mexico 87106 (United States); Gumbs, Godfrey [Center for High Technology Materials, University of New Mexico, 1313 Goddard St SE, Albuquerque, New Mexico 87106 (United States); Abranyos, Yonatan [Department of Physics and Astronomy, Hunter College of the City University of New York, 695 Park Avenue, New York, New York 10065 (United States); Pepper, Michael; Kumar, Sanjeev [Department of Electronic and Electrical Engineering, University College London, London, WC1E 7JE (United Kingdom); London Centre for Nanotechnology, 17-19 Gordon Street, London, WC1H 0AH (United Kingdom)

2015-11-15

For quantum ballistic transport of electrons through a short conduction channel, the role of Coulomb interaction may significantly modify the energy levels of two-electron states at low temperatures as the channel becomes wide. In this regime, the Coulomb effect on the two-electron states is calculated and found to lead to four split energy levels, including two anticrossing-level and two crossing-level states. Moreover, due to the interplay of anticrossing and crossing effects, our calculations reveal that the ground two-electron state will switch from one anticrossing state (strong confinement) to a crossing state (intermediate confinement) as the channel width gradually increases and then back to the original anticrossing state (weak confinement) as the channel width becomes larger than a threshold value. This switching behavior leaves a footprint in the ballistic conductance as well as in the diffusion thermoelectric power of electrons. Such a switching is related to the triple spin degeneracy as well as to the Coulomb repulsion in the central region of the channel, which separates two electrons away and pushes them to different channel edges. The conductance reoccurrence region expands from the weak to the intermediate confinement regime with increasing electron density.

Turbulence and transport of passive scalar in magnetohydrodynamic channel flows with different orientations of magnetic field

International Nuclear Information System (INIS)

Dey, Prasanta K.; Zikanov, Oleg

2012-01-01

Highlights: ► Turbulent passive scalar transport in an MHD flow in a channel is studied using DNS. ► Magnetic fields of wall-normal, spanwise, and streamwise orientations are considered. ► Magnetic fields suppress turbulent transport and modifies scalar distribution. ► The effect is particularly strong at wall-normal and spanwise magnetic fields. ► Decrease of Nusselt number is approximated by a linear function of magnetic interaction parameter. - Abstract: DNS of turbulent flow and passive scalar transport in a channel are conducted for the situation when the fluid is electrically conducting (for example, a liquid metal) and the flow is affected by an imposed magnetic field. The cases of wall-normal, spanwise, and streamwise orientation of the magnetic field are considered. As main results, we find that the magnetic fields, especially those in the wall-normal and spanwise directions, significantly reduce the turbulent scalar transport and modify the properties of the scalar distribution.

Transport of nano-objects in narrow channels: influence of Brownian diffusion, confinement and particle nature.

Science.gov (United States)

Liot, O; Socol, M; Garcia, L; Thiéry, J; Figarol, A; Mingotaud, A F; Joseph, P

2018-06-13

This paper presents experimental results about transport of dilute suspensions of nano-objects in silicon-glass micrometric and sub-micrometric channels. Two kinds of objects are used: solid, rigid latex beads and spherical capsule-shaped, soft polymersomes. They are tracked using fluorescence microscopy. Three aspects are studied: confinement (ratio between particle diameter and channel depth), Brownian diffusion and particle nature. The aim of this work is to understand how these different aspects affect the transport of suspensions in narrow channels and to understand the different mechanisms at play. Concerning the solid beads we observe the appearance of two regimes, one where the experimental mean velocity is close to the expected one and another where this velocity is lower. This is directly related to a competition between confinement, Brownian diffusion and advection. These two regimes are shown to be linked to the inhomogeneity of particles distribution in the channel depth, which we experimentally deduce from velocity distributions. This inhomogeneity appears during the entrance process into the sub-micrometric channels, as for hydrodynamic separation or deterministic lateral displacement. Concerning the nature of the particles we observed a shift of transition towards the second regime likely due to the relationships between shear stress and polymersomes mechanical properties which could reduce the inhomogeneity imposed by the geometry of our device.

Transport of nano-objects in narrow channels: influence of Brownian diffusion, confinement and particle nature

Science.gov (United States)

Liot, O.; Socol, M.; Garcia, L.; Thiéry, J.; Figarol, A.; Mingotaud, A. F.; Joseph, P.

2018-06-01

This paper presents experimental results about transport of dilute suspensions of nano-objects in silicon-glass micrometric and sub-micrometric channels. Two kinds of objects are used: solid, rigid latex beads and spherical capsule-shaped, soft polymersomes. They are tracked using fluorescence microscopy. Three aspects are studied: confinement (ratio between particle diameter and channel depth), Brownian diffusion and particle nature. The aim of this work is to understand how these different aspects affect the transport of suspensions in narrow channels and to understand the different mechanisms at play. Concerning the solid beads we observe the appearance of two regimes, one where the experimental mean velocity is close to the expected one and another where this velocity is lower. This is directly related to a competition between confinement, Brownian diffusion and advection. These two regimes are shown to be linked to the inhomogeneity of particles distribution in the channel depth, which we experimentally deduce from velocity distributions. This inhomogeneity appears during the entrance process into the sub-micrometric channels, as for hydrodynamic separation or deterministic lateral displacement. Concerning the nature of the particles we observed a shift of transition towards the second regime likely due to the relationships between shear stress and polymersomes mechanical properties which could reduce the inhomogeneity imposed by the geometry of our device.

Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium.

Science.gov (United States)

Hahn, Anne; Faulhaber, Johannes; Srisawang, Lalita; Stortz, Andreas; Salomon, Johanna J; Mall, Marcus A; Frings, Stephan; Möhrlen, Frank

2017-06-01

Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca 2+ or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca 2+ - dependent and cAMP- dependent Cl - secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca 2+ -gated Cl - channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel, the epithelial Na + channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium. The contribution of ANO1 channels to nucleotide-stimulated Cl - secretion was determined using the channel blocker Ani9 in short-circuit current recordings obtained from primary cultures of rat tracheal epithelial cells in Ussing chambers. We found that ANO1, CFTR and AQP5 proteins were expressed in nonciliated cells of the tracheal epithelium, whereas ENaC was expressed in ciliated cells. Among nonciliated cells, ANO1 occurred together with CFTR and Muc5b and, in addition, in a different cell type without CFTR and Muc5b. Bioelectrical studies with the ANO1-blocker Ani9 indicated that ANO1 mediated the secretory response to the nucleotide uridine-5'-triphosphate. Our data demonstrate that, in rat tracheal epithelium, Cl - secretion and Na + absorption are routed through different cell types, and that ANO1 channels form the molecular basis of Ca 2+ -dependent Cl - secretion in this tissue. These characteristic features of Cl - -dependent secretion reveal similarities and distinct differences to secretory processes in human airways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Intrathecal infusion of a Ca(2+)-permeable AMPA channel blocker slows loss of both motor neurons and of the astrocyte glutamate transporter, GLT-1 in a mutant SOD1 rat model of ALS.

Science.gov (United States)

Yin, Hong Z; Tang, Darryl T; Weiss, John H

2007-10-01

Elevated extracellular glutamate, resulting from a loss of astrocytic glutamate transport capacity, may contribute to excitotoxic motor neuron (MN) damage in ALS. Accounting for their high excitotoxic vulnerability, MNs possess large numbers of unusual Ca(2+)-permeable AMPA channels (Ca-AMPA channels), the activation of which triggers mitochondrial Ca(2+) overload and strong reactive oxygen species (ROS) generation. However, the causes of the astrocytic glutamate transport loss remain unexplained. To assess the role of Ca-AMPA channels on the evolution of pathology in vivo, we have examined effects of prolonged intrathecal infusion of the Ca-AMPA channel blocker, 1-naphthyl acetylspermine (NAS), in G93A transgenic rat models of ALS. In wild-type animals, immunoreactivity for the astrocytic glutamate transporter, GLT-1, was particularly strong around ventral horn MNs. However, a marked loss of ventral horn GLT-1 was observed, along with substantial MN damage, prior to onset of symptoms (90-100 days) in the G93A rats. Conversely, labeling with the oxidative marker, nitrotyrosine, was increased in the neuropil surrounding MNs in the transgenic animals. Compared to sham-treated G93A animals, 30-day NAS infusions (starting at 67+/-2 days of age) markedly diminished the loss of both MNs and of astrocytic GLT-1 labeling. These observations are compatible with the hypothesis that activation of Ca-AMPA channels on MNs contributes, likely in part through oxidative mechanisms, to loss of glutamate transporter in surrounding astrocytes.

Effect of wall compliance on peristaltic transport of a Newtonian fluid in an asymmetric channel

Directory of Open Access Journals (Sweden)

Mohamed H. Haroun

2006-01-01

Full Text Available Peristaltic transport of an incompressible viscous fluid in an asymmetric compliant channel is studied. The channel asymmetry is produced by choosing the peristaltic wave train on the walls to have different amplitudes and phases. The fluid-solid interaction problem is investigated by considering equations of motion of both the fluid and the deformable boundaries. The driving mechanism of the muscle is represented by assuming the channel walls to be compliant. The phenomenon of the “mean flow reversal” is discussed. The effect of wave amplitude ratio, width of the channel, phase difference, wall elastance, wall tension, and wall damping on mean-velocity and reversal flow has been investigated. The results reveal that the reversal flow occurs near the boundaries which is not possible in the elastic symmetric channel case.

Electrostatics of aquaporin and aquaglyceroporin channels correlates with their transport selectivity

Science.gov (United States)

Oliva, Romina; Calamita, Giuseppe; Thornton, Janet M.; Pellegrini-Calace, Marialuisa

2010-01-01

Aquaporins are homotetrameric channel proteins, which allow the diffusion of water and small solutes across biological membranes. According to their transport function, aquaporins can be divided into “orthodox aquaporins”, which allow the flux of water molecules only, and “aquaglyceroporins”, which facilitate the diffusion of glycerol and other small solutes in addition to water. The contribution of individual residues in the pore to the selectivity of orthodox aquaporins and aquaglyceroporins is not yet fully understood. To gain insights into aquaporin selectivity, we focused on the sequence variation and electrostatics of their channels. The continuum Poisson-Boltzmann electrostatic potential along the channel was calculated and compared for ten three-dimensional-structures which are representatives of different aquaporin subfamilies, and a panel of functionally characterized mutants, for which high-accuracy three-dimensional-models could be derived. Interestingly, specific electrostatic profiles associated with the main selectivity to water or glycerol could be identified. In particular: (i) orthodox aquaporins showed a distinctive electrostatic potential maximum at the periplasmic side of the channel around the aromatic/Arg (ar/R) constriction site; (ii) aquaporin-0 (AQP0), a mammalian aquaporin with considerably low water permeability, had an additional deep minimum at the cytoplasmic side; (iii) aquaglyceroporins showed a rather flat potential all along the channel; and (iv) the bifunctional protozoan PfAQP had an unusual all negative profile. Evaluation of electrostatics of the mutants, along with a thorough sequence analysis of the aquaporin pore-lining residues, illuminated the contribution of specific residues to the electrostatics of the channels and possibly to their selectivity. PMID:20147624

Proton and non-proton activation of ASIC channels.

Directory of Open Access Journals (Sweden)

Ivan Gautschi

Full Text Available The Acid-Sensing Ion Channels (ASIC exhibit a fast desensitizing current when activated by pH values below 7.0. By contrast, non-proton ligands are able to trigger sustained ASIC currents at physiological pHs. To analyze the functional basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two distinct currents, a proton-induced desensitizing current and a sustained current triggered by sulfhydryl reagents. These currents differ in their pH dependency, their sensitivity to the sulfhydryl reagents, their ionic selectivity and their relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the channels can function in two distinct modes, a desensitizing mode and a sustained mode depending on the activating ligands. The pore vestibule of the channel represents a functional site for binding non-proton ligands to activate ASIC1 and ASIC2 at neutral pH and to prevent channel desensitization.

Proton and non-proton activation of ASIC channels.

Science.gov (United States)

Gautschi, Ivan; van Bemmelen, Miguel Xavier; Schild, Laurent

2017-01-01

The Acid-Sensing Ion Channels (ASIC) exhibit a fast desensitizing current when activated by pH values below 7.0. By contrast, non-proton ligands are able to trigger sustained ASIC currents at physiological pHs. To analyze the functional basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two distinct currents, a proton-induced desensitizing current and a sustained current triggered by sulfhydryl reagents. These currents differ in their pH dependency, their sensitivity to the sulfhydryl reagents, their ionic selectivity and their relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the channels can function in two distinct modes, a desensitizing mode and a sustained mode depending on the activating ligands. The pore vestibule of the channel represents a functional site for binding non-proton ligands to activate ASIC1 and ASIC2 at neutral pH and to prevent channel desensitization.

Tracer transport in fractures: analysis of field data based on a variable - aperture channel model

International Nuclear Information System (INIS)

Tsang, C.F.; Tsang, Y.W.; Hale, F.V.

1991-06-01

A variable-aperture channel model is used as the basis to interpret data from a three-year tracer transport experiment in fractured rocks. The data come from the so-called Stripa-3D experiment performed by Neretnieks and coworkers. Within the framework of the variable-aperture channel conceptual model, tracers are envisioned as travelling along a number of variable-aperture flow channels, whose properties are related to the mean b - and standard deviation σ b of the fracture aperture distribution. Two methods are developed to address the presence of strong time variation of the tracer injection flow rate in this experiment. The first approximates the early part of the injection history by an exponential decay function and is applicable to the early time tracer breakthrough data. The second is a deconvolution method involving the use of Toeplitz matrices and is applicable over the complete period of variable injection of the tracers. Both methods give consistent results. These results include not only estimates of b and σ, but also ranges of Peclet numbers, dispersivity and an estimate of the number of channels involved in the tracer transport. An interesting and surprising observation is that the data indicate that the Peclet number increases with the mean travel time: i.e., dispersivity decreasing with mean travel time. This trend is consistent with calculated results of tracer transport in multiple variable-aperture fractures in series. The meaning of this trend is discussed in terms of the strong heterogeneity of the flow system. (au) (22 refs.)

BAD and KATP channels regulate neuron excitability and epileptiform activity.

Science.gov (United States)

Martínez-François, Juan Ramón; Fernández-Agüera, María Carmen; Nathwani, Nidhi; Lahmann, Carolina; Burnham, Veronica L; Danial, Nika N; Yellen, Gary

2018-01-25

Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad ( B CL-2 a gonist of cell d eath) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (K ATP ) channels. Here we investigated the effect of BAD manipulation on K ATP channel activity and excitability in acute brain slices. We found that BAD's influence on neuronal K ATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal K ATP channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of K ATP channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a 'dentate gate' function that is reinforced by increased K ATP channel activity. © 2018, Martínez-François et al.

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.

Sediment and Vegetation Controls on Delta Channel Networks

Science.gov (United States)

Lauzon, R.; Murray, A. B.; Piliouras, A.; Kim, W.

2016-12-01

Numerous factors control the patterns of distributary channels formed on a delta, including water and sediment discharge, grain size, sea level rise rates, and vegetation type. In turn, these channel networks influence the shape and evolution of a delta, including what types of plant and animal life - such as humans - it can support. Previous fluvial modeling and flume experiments, outside of the delta context, have addressed how interactions between sediment and vegetation, through their influence on lateral transport of sediment, determine what type of channel networks develops. Similar interactions likely also shape delta flow patterns. Vegetation introduces cohesion, tending to reduce channel migration rates and strengthen existing channel banks, reinforcing existing channels and resulting in localized, relatively stable flow patterns. On the other hand, sediment transport processes can result in lateral migration and frequent switching of active channels, resulting in flow resembling that of a braided stream. While previous studies of deltas have indirectly explored the effects of vegetation through the introduction of cohesive sediment, we directly incorporate key effects of vegetation on flow and sediment transport into the delta-building model DeltaRCM to explore how these effects influence delta channel network formation. Model development is informed by laboratory flume experiments at UT Austin. Here we present initial results of experiments exploring the effects of sea level rise rate, sediment grain size, vegetation type, and vegetation growth rate on delta channel network morphology. These results support the hypothesis that the ability for lateral transport of sediment to occur plays a key role in determining the evolution of delta channel networks and delta morphology.

Activation of ERG2 potassium channels by the diphenylurea NS1643

DEFF Research Database (Denmark)

Elmedyb, Pernille; Olesen, Søren-Peter; Grunnet, Morten

2007-01-01

Three members of the ERG potassium channel family have been described (ERG1-3 or Kv 11.1-3). ERG1 is by far the best characterized subtype and it constitutes the molecular component of the cardiac I(Kr) current. All three channel subtypes are expressed in neurons but their function remains unclear....... The lack of functional information is at least partly due to the lack of specific pharmacological tools. The compound NS1643 has earlier been reported as an ERG1 channel activator. We found that NS1643 also activates the ERG2 channel; however, the molecular mechanism of the activation differs between...... the ERG1 and ERG2 channels. This is surprising since ERG1 and ERG2 channels have very similar biophysical and structural characteristics. For ERG2, NS1643 causes a left-ward shift of the activation curve, a faster time-constant of activation and a slower time-constant of inactivation as well...

Split-Channel Ballistic Transport in an InSb Nanowire

Science.gov (United States)

Estrada Saldaña, Juan Carlos; Niquet, Yann-Michel; Cleuziou, Jean-Pierre; Lee, Eduardo J. H.; Car, Diana; Plissard, Sébastien R.; Bakkers, Erik P. A. M.; De Franceschi, Silvano

2018-04-01

We report an experimental study of one-dimensional (1D) electronic transport in an InSb semiconducting nanowire. Three bottom gates are used to locally deplete the nanowire creating a ballistic quantum point contact with only a few conducting channels. In a magnetic field, the Zeeman splitting of the corresponding 1D subbands is revealed by the emergence of conductance plateaus at multiples of $e^2$/h, yet we find a quantized conductance pattern largely dependent on the configuration of voltages applied to the bottom gates. In particular, we can make the first plateau disappear leaving a first conductance step of 2$e^2/h$, which is indicative of a remarkable two-fold subband degeneracy that can persist up to several Tesla. For certain gate voltage settings, we also observe the presence of discrete resonant states producing conductance features that can resemble those expected from the opening of a helical gap in the subband structure. We explain our experimental findings through the formation of two spatially separated 1D conduction channels.

Plasma channel and Z-pinch dynamics for heavy ion transport

Energy Technology Data Exchange (ETDEWEB)

Ponce-Marquez, David [Univ. of California, Berkeley, CA (United States)

2002-01-01

A self stabilized, free standing, z-pinch plasma channel has been proposed to deliver the high intensity heavy ion beam from the end of a driver to the fuel target in a heavy ion inertial fusion power plant. The z-pinch relaxes emittance and energy spread requirements requiring a lower cost driver. A z-pinch transport would reduce the number of beam entry port holes to the target chamber from over a hundred to four as compared to neutralized ballistic focusing thus reducing the driver hardware exposure to neutron flux. Experiments where a double pulse discharge technique is used, z-pinch plasma channels with enhanced stability are achieved. Typical parameters are 7 kV pre-pulse discharge and 30 kV main bank discharge with 50 kA of channel current in a 7 torr background gas atmosphere. This work is an experimental study of these plasma channels examining the relevant physics necessary to understand and model such plasmas. Laser diagnostics measured the dynamical properties of neutrals and plasma. Schlieren and phase contrast techniques probe the pre-pulse gas dynamics and infrared interferometry and faraday effect polarimetry are used on the z-pinch to study its electron density and current distribution. Stability and repeatability of the z-pinch depend on the initial conditions set by the pre-pulse. Results show that the z-pinch channel is wall stabilized by an on-axis gas density depression created by the pre-pulse through hydrodynamic expansion where the ratio of the initial gas density to the final gas density is > 10/1. The low on-axis density favors avalanching along the desired path for the main bank discharge. Pinch time is around 2 s from the main bank discharge initiation with a FWHM of ~ 2 cm. Results also show that typical main bank discharge plasma densities reach 10¹⁷ cm^-3 peak on axis for a 30 kV, 7 torr gas nitrogen discharge. Current rise time is limited by the circuit-channel inductance with the highest contribution to the

Development and applications of the channel network model for simulations of flow and solute transport in fractured rock

International Nuclear Information System (INIS)

Gylling, B.

1997-01-01

The Channel Network model and its computer implementation, the code CHAN3D, for simulations of fluid flow and transport of solutes have been developed. The tool may be used for performance and safety assessments of deep lying repositories in fractured rocks for nuclear and other hazardous wastes, e.g. chemical wastes. It may also be used to simulate and interpret field experiments of flow and transport in large or small scale. Fluid flow and solute transport in fractured media are of interest in the performance assessment of a repository for hazardous waste, located at depth in crystalline rock, with potential release of solutes. Fluid flow in fractured rock is found to be very unevenly distributed due to the heterogeneity of the medium. The water will seek the easiest path, channels, under a prevailing pressure gradient. Solutes in the flowing water may be transported through preferential paths and migrate from the water in the fractures into the stagnant water in the rock matrix. There, sorbing solutes may be sorbed on the micro surfaces within the matrix. The diffusion into the matrix and the sorption process may significantly retard the transport of species and increase the time available for radionuclide decay. Channelling and matrix diffusion contribute to the dispersion of solutes in the water. Important for performance assessment is that channeling may cause a portion of the solutes to arrive much faster than the rest of the solutes. Simulations of field experiments at the Aespoe Hard Rock Laboratory using the Channel Network model have been performed. The application of the model to the site and the simulation results of the pumping and tracer tests are presented. The results show that the model is capable of describing the hydraulic gradient and of predicting flow rates and tracer transport obtained in the experiments. The data requirements for the Channel Network model have been investigated to determine which data are the most important for predictions

A structural view of ligand-dependent activation in thermoTRP channels

Directory of Open Access Journals (Sweden)

Ximena eSteinberg

2014-05-01

Full Text Available Transient Receptor Potential (TRP proteins are a large family of ion channels, grouped intoseven sub-families. Although great advances have been made regarding the activation andmodulation of TRP channel activity, detailed molecular mechanisms governing TRPchannel gating are still needed. Sensitive to electric, chemical, mechanical, and thermalcues, TRP channels are tightly associated with the detection and integration of sensoryinput, emerging as a model to study the polymodal activation of ion channel proteins.Among TRP channels, the temperature-activated kind constitute a subgroup by itself,formed by Vanilloid receptors 1-4, Melastatin receptors 2, 4, 5 and 8, TRPC5, and TRPA1.Some of the so-called thermoTRP channels participate in the detection of noxious stimulimaking them an interesting pharmacological target for the treatment of pain. However, thepoor specificity of the compounds available in the market represents an important obstacleto overcome. Understanding the molecular mechanics underlying ligand-dependentmodulation of TRP channels may help with the rational design of novel syntheticanalgesics. The present review focuses on the structural basis of ligand-dependentactivation of TRPV1 and TRPM8 channels. Special attention is drawn to the dissection ofligand-binding sites within TRPV1, PIP 2 -dependent modulation of TRP channels, and thestructure of natural and synthetic ligands.

Role of aquaporin and sodium channel in pleural water movement.

Science.gov (United States)

Jiang, Jinjun; Hu, Jie; Bai, Chunxue

2003-12-16

The role of the ENaC sodium channel and aquaporin-1 (AQP1) water channel on pleural fluid dynamics in mice was investigated. 0.25 ml of hypertonic or isosmolar fluid was infused into the pleural space in anesthetized wildtype and AQP1 null mice. Pleural fluid was sampled at specified times to quantify the osmolality and volume. The sodium channel activator terbutaline increased isosmolar fluid clearance by 90% while the sodium channel inhibitor amiloride decreased it by 15%, but had no effect on osmotically driven water transport. AQP1 deletion significantly decreased osmotic water transport in pleural space by twofold, but it had no effect on isosmolar fluid clearance. Pretreatment with dexamethasone increased pleural osmotic fluid entry by 25%, while intravenous injection of HgCl2 decreased osmotic pleural water movement by 43%. These results provided evidence for a role of a sodium channel in pleural fluid absorption; AQP1 plays a major role in osmotic liquid transport but it does not affect isosmolar fluid clearance.

Channel-accelerating gap interaction and beam acceleration and transport experiments with the recirculating linear accelerator (RLA)

International Nuclear Information System (INIS)

Mazarakis, M.G.; Smith, D.L.; Poukey, J.W.; Wagner, J.S.; Bennett, L.F.; Olson, W.R.; Turman, B.N.; Prestwich, K.R.; Wells, J.; Struve, K.

1992-01-01

The lifetime of the Ion Focusing Regime (IFR) channel following the pulsing of the post-accelerating gaps is critical for open-ended low energy devices. It dictates the number of allowable beam recirculations through the gaps. In the case of a closed racetrack configuration, it is significant but not as critical, since the presence of the electron beam focuses the ions and lengthens the lifetime of the ion channel. The authors have experimentally established that pulsing an accelerating gap perturbs the IFR channel. However for the parameters studied, the lifetime is long enough to allow at least four beam recirculations in a spiral device. In addition transparent grids of cusp fields positioned upstream and downstream from the gaps prevent them from perturbing the IFR channel. Experiments were performed with and without injected electron beams. For the experiments investigating the IFR channel interaction with the accelerating gap, the injector was removed and the beam line was extended downstream and upstream from the accelerating cavity. Only the first straight section of the RLA with one accelerating cavity (ET-2) was utilized. The acceleration and transport experiments were performed utilizing two injectors: first the low energy 1.3-MV Isolated Blumlein (IB) injector and most recently the new 4-MV 20-kA injector. Beams of 6--20 kA current were produced and successfully transported and accelerated through the ET-2 post-accelerating gap. For both injectors an apertured non-immersed ion-focused foilless diode was selected among various options. It is the simplest and easiest to operate and can be adjusted to provide variable beam impedance loads to the injector. The transport efficiencies were 90% for the low energy injector and 100% for the new 4-MV injector. The beam Gaussian profile and radius (5 mm) remain the same through acceleration. Experimental results will be presented and compared with numerical simulations

Two-photon activation of endogenous store-operated calcium channels without optogenetics

Science.gov (United States)

Cheng, Pan; Tang, Wanyi; He, Hao

2018-02-01

Store-operated calcium (SOC) channels, regulated by intracellular Ca2+ store, are the essential pathway of calcium signaling and participate in a wide variety of cellular activities such as gene expression, secretion and immune response1. However, our understanding and regulation of SOC channels are mainly based on pharmacological methods. Considering the unique advantages of optical control, optogenetic control of SOC channels has been developed2. However, the process of genetic engineering to express exogenous light-sensitive protein is complicated, which arouses concerns about ethic difficulties in some research of animal and applications in human. In this report, we demonstrate rapid, robust and reproducible two-photon activation of endogenous SOC channels by femtosecond laser without optogenetics. We present that the short-duration two-photon scanning on subcellular microregion induces slow Ca2+ influx from extracellular medium, which can be eliminated by removing extracellular Ca2+. Block of SOC channels using various pharmacological inhibitors or knockdown of SOC channels by RNA interference reduce the probability of two-photon activated Ca2+ influx. On the contrary, overexpression of SOC channels can increase the probability of Ca2+ influx by two-photon scanning. These results collectively indicate Ca2+ influx through two-photon activated SOC channels. Different from classical pathway of SOC entry activated by Ca2+ store depletion, STIM1, the sensor protein of Ca2+ level in endoplasmic reticulum, does not show any aggregation or migration in this two-photon activated Ca2+ influx, which rules out the possibility of intracellular Ca2+ store depletion. Thereby, we propose this all-optical method of two-photon activation of SOC channels is of great potential to be widely applied in the research of cell calcium signaling and related biological research.

Transport coefficients for electrolytes in arbitrarily shaped nano- and microfluidic channels

DEFF Research Database (Denmark)

Mortensen, Niels Asger; Olesen, Laurits Højgaard; Bruus, Henrik

2006-01-01

for the hydraulic and electrical transport coefficients which satisfy Onsager relations. In the limit of non-overlapping Debye layers, the transport coefficients are simply expressed in terms of parameters of the electrolyte as well as the geometrical correction factor for the Hagen-Poiseuille part of the problem....... In particular, we consider the limits of thin non-overlapping as well as strongly overlapping Debye layers, respectively, and calculate the corrections to the hydraulic resistance due to electro-hydrodynamic interactions.......We consider laminar flow of incompressible electrolytes in long, straight channels driven by pressure and electro-osmosis. We use a Hilbert space eigenfunction expansion to address the general problem of an arbitrary cross-section and obtain general results in linear-response theory...

Cell volume and membrane stretch independently control K+ channel activity

DEFF Research Database (Denmark)

Bomholtz, Sofia Hammami; Willumsen, Niels J; Olsen, Hervør L

2009-01-01

A number of potassium channels including members of the KCNQ family and the Ca(2+) activated IK and SK, but not BK, are strongly and reversibly regulated by small changes in cell volume. It has been argued that this general regulation is mediated through sensitivity to changes in membrane stretch...... was not affected by membrane stretch. The results indicate that (1) activation of BK channels by local membrane stretch is not mimicked by membrane stress induced by cell swelling, and (2) activation of KCNQ1 channels by cell volume increase is not mediated by local tension in the cell membrane. We conclude....... To test this hypothesis we have studied the regulation of KCNQ1 and BK channels after expression in Xenopus oocytes. Results from cell-attached patch clamp studies (approximately 50 microm(2) macropatches) in oocytes expressing BK channels demonstrate that the macroscopic volume-insensitive BK current...

Coassembly of big conductance Ca2+-activated K+ channels and L-type voltage-gated Ca2+ channels in rat brain

DEFF Research Database (Denmark)

Grunnet, Morten; Kaufmann, Walter A

2004-01-01

Based on electrophysiological studies, Ca(2+)-activated K(+) channels and voltage-gated Ca(2+) channels appear to be located in close proximity in neurons. Such colocalization would ensure selective and rapid activation of K(+) channels by local increases in the cytosolic calcium concentration...

Suppression of adenosine-activated chloride transport by ethanol in airway epithelia.

Directory of Open Access Journals (Sweden)

Sammeta V Raju

Full Text Available Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR, a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B adenosine receptor (A(2BAR, largely abolished the adenosine-stimulated chloride transport, suggesting that A(2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.

The role of an ancestral hyperpolarization-activated cyclic nucleotide-gated K+ channel in branchial acid-base regulation in the green crab, Carcinus maenas.

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Fehsenfeld, Sandra; Weihrauch, Dirk

2016-03-01

Numerous electrophysiological studies on branchial K(+) transport in brachyuran crabs have established an important role for potassium channels in osmoregulatory ion uptake and ammonia excretion in the gill epithelium of decapod crustaceans. However, hardly anything is known of the actual nature of these channels in crustaceans. In the present study, the identification of a hyperpolarization-activated cyclic nucleotide-gated potassium channel (HCN) in the transcriptome of the green crab Carcinus maenas and subsequent performance of quantitative real-time PCR revealed the ubiquitous expression of this channel in this species. Even though mRNA expression levels in the cerebral ganglion were found to be approximately 10 times higher compared with all other tissues, posterior gills still expressed significant levels of HCN, indicating an important role for this transporter in branchial ion regulation. The relatively unspecific K(+)-channel inhibitor Ba(2+), as well as the HCN-specific blocker ZD7288, as applied in gill perfusion experiments and electrophysiological studies employing the split gill lamellae revealed the presence of at least two different K(+)/NH4(+)-transporting structures in the branchial epithelium of C. maenas. Furthermore, HCN mRNA levels in posterior gill 7 decreased significantly in response to the respiratory or metabolic acidosis that was induced by acclimation of green crabs to high environmental PCO2 and ammonia, respectively. Consequently, the present study provides first evidence that HCN-promoted NH4(+) epithelial transport is involved in both branchial acid-base and ammonia regulation in an invertebrate. © 2016. Published by The Company of Biologists Ltd.

Preliminary assessment of channel stability and bed-material transport in the Tillamook Bay tributaries and Nehalem River basin, northwestern Oregon

Science.gov (United States)

Jones, Krista L.; Keith, Mackenzie K.; O'Connor, Jim E.; Mangano, Joseph F.; Wallick, J. Rose

2012-01-01

subject to incision and aggradation as well as lateral shifts in thalweg position and bank deposition and erosion. * In fluvial reaches, unit bar area declined a net 5.3-83.6 percent from 1939 to 2009. The documented reduction in bar area may be attributable to several factors, including vegetation establishment and stabilization of formerly active bar surfaces, lateral channel changes and resulting alterations in sediment deposition and erosion patterns, and streamflow and/or tide differences between photographs. Other factors that may be associated with the observed reduction in bar area but not assessed in this reconnaissance level study include changes in the sediment and hydrology regimes of these rivers over the analysis period. * In tidal reaches, unit bar area increased on the Tillamook and Nehalem Rivers (98.0 and 14.7 percent, respectively), but declined a net 24.2 to 83.1 percent in the other four tidal reaches. Net increases in bar area in the Tidal Tillamook and Nehalem Reaches were possibly attributable to tidal differences between the photographs as well as sediment deposition behind log booms and pile structures on the Tillamook River between 1939 and 1967. * The armoring ratio (ratio of the median grain sizes of a bar's surface and subsurface layers) was 1.6 at Lower Waldron Bar on the Miami River, tentatively indicating a relative balance between transport capacity and sediment supply at this location. Armoring ratios, however, ranged from 2.4 to 5.5 at sites on the Trask, Wilson, Kilchis, and Nehalem Rivers; these coarse armor layers probably reflect limited bed-material supply at these sites. * On the basis of mapping results, measured armoring ratios, and channel cross section surveys, preliminary conclusions are that the fluvial reaches on the Tillamook, Trask, Kilchis, and Nehalem Rivers are currently sediment supply-limited in terms of bed material - that is, the transport capacity of the channel generally exceeds the supply of bed material. The

Piezo proteins are pore-forming subunits of mechanically activated channels.

Science.gov (United States)

Coste, Bertrand; Xiao, Bailong; Santos, Jose S; Syeda, Ruhma; Grandl, Jörg; Spencer, Kathryn S; Kim, Sung Eun; Schmidt, Manuela; Mathur, Jayanti; Dubin, Adrienne E; Montal, Mauricio; Patapoutian, Ardem

2012-02-19

Mechanotransduction has an important role in physiology. Biological processes including sensing touch and sound waves require as-yet-unidentified cation channels that detect pressure. Mouse Piezo1 (MmPiezo1) and MmPiezo2 (also called Fam38a and Fam38b, respectively) induce mechanically activated cationic currents in cells; however, it is unknown whether Piezo proteins are pore-forming ion channels or modulate ion channels. Here we show that Drosophila melanogaster Piezo (DmPiezo, also called CG8486) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. MmPiezo1 assembles as a ∼1.2-million-dalton homo-oligomer, with no evidence of other proteins in this complex. Purified MmPiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium-red-sensitive ion channels. These data demonstrate that Piezo proteins are an evolutionarily conserved ion channel family involved in mechanotransduction.

Characterization of the human pH- and PKA-activated ClC-2G(2 alpha) Cl- channel.

Science.gov (United States)

Sherry, A M; Stroffekova, K; Knapp, L M; Kupert, E Y; Cuppoletti, J; Malinowska, D H

1997-08-01

A ClC-2G(2 alpha) Cl- channel was identified to be present in human lung and stomach, and a partial cDNA for this Cl- channel was cloned from a human fetal lung library. A full-length expressible human ClC-2G(2 alpha) cDNA was constructed by ligation of mutagenized expressible rabbit ClC-2G(2 alpha) cDNA with the human lung ClC-2G(2 alpha) cDNA, expressed in oocytes, and characterized at the single-channel level. Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) treatment increased the probability of opening of the channel (Po). After PKA activation, the channel exhibited a linear (r = 0.99) current-voltage curve with a slope conductance of 22.1 +/- 0.8 pS in symmetric 800 mM tetraethylammonium chloride (TEACl; pH 7.4). Under fivefold gradient conditions of TEACl, a reversal potential of +21.5 +/- 2.8 mV was measured demonstrating anion-to-cation discrimination. As previously demonstrated for the rabbit ClC-2G(2 alpha) Cl- channel, the human analog, hClC-2G(2 alpha), was active at pH 7.4 as well as when the pH of the extracellular face of the channel (trans side of the bilayer; pHtrans) was asymmetrically reduced to pH 3.0. The extent of PKA activation was dependent on pHtrans. With PKA treatment, Po increased fourfold with a pHtrans of 7.4 and eightfold with a pHtrans of 3.0. Effects of sequential PKA addition followed by pHtrans reduction on the same channel suggested that the PKA- and pH-dependent increases in channel Po were separable and cumulative. Northern analysis showed ClC-2G(2 alpha) mRNA to be present in human adult and fetal lung and adult stomach, and quantitative reverse transcriptase-polymerase chain reaction showed this channel to be present in the adult human lung and stomach at about one-half the level found in fetal lung. The findings of the present study suggest that the ClC-2G(2 alpha) Cl- channel may play an important role in Cl- transport in the fetal and adult human lung.

Channel-forming activities in the glycosomal fraction from the bloodstream form of Trypanosoma brucei.

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Melisa Gualdron-López

Full Text Available BACKGROUND: Glycosomes are a specialized form of peroxisomes (microbodies present in unicellular eukaryotes that belong to the Kinetoplastea order, such as Trypanosoma and Leishmania species, parasitic protists causing severe diseases of livestock and humans in subtropical and tropical countries. The organelles harbour most enzymes of the glycolytic pathway that is responsible for substrate-level ATP production in the cell. Glycolysis is essential for bloodstream-form Trypanosoma brucei and enzymes comprising this pathway have been validated as drug targets. Glycosomes are surrounded by a single membrane. How glycolytic metabolites are transported across the glycosomal membrane is unclear. METHODS/PRINCIPAL FINDINGS: We hypothesized that glycosomal membrane, similarly to membranes of yeast and mammalian peroxisomes, contains channel-forming proteins involved in the selective transfer of metabolites. To verify this prediction, we isolated a glycosomal fraction from bloodstream-form T. brucei and reconstituted solubilized membrane proteins into planar lipid bilayers. The electrophysiological characteristics of the channels were studied using multiple channel recording and single channel analysis. Three main channel-forming activities were detected with current amplitudes 70-80 pA, 20-25 pA, and 8-11 pA, respectively (holding potential +10 mV and 3.0 M KCl as an electrolyte. All channels were in fully open state in a range of voltages ±150 mV and showed no sub-conductance transitions. The channel with current amplitude 20-25 pA is anion-selective (P(K+/P(Cl-∼0.31, while the other two types of channels are slightly selective for cations (P(K+/P(Cl- ratios ∼1.15 and ∼1.27 for the high- and low-conductance channels, respectively. The anion-selective channel showed an intrinsic current rectification that may suggest a functional asymmetry of the channel's pore. CONCLUSIONS/SIGNIFICANCE: These results indicate that the membrane of glycosomes

Activation of TRPM7 channels by small molecules under physiological conditions.

Science.gov (United States)

Hofmann, T; Schäfer, S; Linseisen, M; Sytik, L; Gudermann, T; Chubanov, V

2014-12-01

Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a cation channel covalently linked to a protein kinase domain. TRPM7 is ubiquitously expressed and regulates key cellular processes such as Mg(2+) homeostasis, motility, and proliferation. TRPM7 is involved in anoxic neuronal death, cardiac fibrosis, and tumor growth. The goal of this work was to identify small molecule activators of the TRPM7 channel and investigate their mechanism of action. We used an aequorin bioluminescence-based assay to screen for activators of the TRPM7 channel. Valid candidates were further characterized using patch clamp electrophysiology. We identified 20 drug-like compounds with various structural backbones that can activate the TRPM7 channel. Among them, the δ opioid antagonist naltriben was studied in greater detail. Naltriben's action was selective among the TRP channels tested. Naltriben activates TRPM7 currents without prior depletion of intracellular Mg(2+) even under conditions of low PIP2. Moreover, naltriben interfered with the effect of the TRPM7 inhibitor NS8593. Finally, our experiments with TRPM7 variants carrying mutations in the pore, TRP, and kinase domains indicate that the site of TRPM7 activation by this small-molecule ligand is most likely located in or near the TRP domain. In conclusion, we identified the first organic small-molecule activators of TRPM7 channels, thus providing new experimental tools to study TRPM7 function in native cellular environments.

C-terminus-mediated voltage gating of Arabidopsis guard cell anion channel QUAC1.

Science.gov (United States)

Mumm, Patrick; Imes, Dennis; Martinoia, Enrico; Al-Rasheid, Khaled A S; Geiger, Dietmar; Marten, Irene; Hedrich, Rainer

2013-09-01

Anion transporters in plants play a fundamental role in volume regulation and signaling. Currently, two plasma membrane-located anion channel families—SLAC/SLAH and ALMT—are known. Among the ALMT family, the root-expressed ALuminium-activated Malate Transporter 1 was identified by comparison of aluminum-tolerant and Al(3+)-sensitive wheat cultivars and was subsequently shown to mediate voltage-independent malate currents. In contrast, ALMT12/QUAC1 (QUickly activating Anion Channel1) is expressed in guard cells transporting malate in an Al(3+)-insensitive and highly voltage-dependent manner. So far, no information is available about the structure and mechanism of voltage-dependent gating with the QUAC1 channel protein. Here, we analyzed gating of QUAC1-type currents in the plasma membrane of guard cells and QUAC1-expressing oocytes revealing similar voltage dependencies and activation–deactivation kinetics. In the heterologous expression system, QUAC1 was electrophysiologically characterized at increasing extra- and intracellular malate concentrations. Thereby, malate additively stimulated the voltage-dependent QUAC1 activity. In search of structural determinants of the gating process, we could not identify transmembrane domains common for voltage-sensitive channels. However, site-directed mutations and deletions at the C-terminus of QUAC1 resulted in altered voltage-dependent channel activity. Interestingly, the replacement of a single glutamate residue, which is conserved in ALMT channels from different clades, by an alanine disrupted QUAC1 activity. Together with C- and N-terminal tagging, these results indicate that the cytosolic C-terminus is involved in the voltage-dependent gating mechanism of QUAC1.

Generic transmission zeros in time-reversal symmetric single channel transport through quasi-1d systems

International Nuclear Information System (INIS)

Lee, H. W.

1999-01-01

Wh study phase coherent transport in a single channel system using the scattering matrix approach. It is show that the Friedel sum rule and the time-reversal symmetry result in the generic appearance of transmission zeros in quasi-1d systems. The transmission zeros naturally lead to abrupt phase changes (without any intrinsic energy scale) and in-phase resonances, thus providing insights to recent experiments on phase coherent transport through a quantum dot

Active Transportation Surveillance - United States, 1999-2012.

Science.gov (United States)

Whitfield, Geoffrey P; Paul, Prabasaj; Wendel, Arthur M

2015-08-28

Physical activity is a health-enhancing behavior, and most U.S. adults do not meet the 2008 Physical Activity Guidelines for Americans. Active transportation, such as by walking or bicycling, is one way that persons can be physically active. No comprehensive, multiyear assessments of active transportation surveillance in the United States have been conducted. 1999-2012. Five surveillance systems assess one or more components of active transportation. The American Community Survey and the National Household Travel Survey (NHTS) both assess the mode of transportation to work in the past week. From these systems, the proportion of respondents who reported walking or bicycling to work can be calculated. NHTS and the American Time Use Survey include 1-day assessments of trips or activities. With that information, the proportion of respondents who report any walking or bicycling for transportation can be calculated. The National Health and Nutrition Examination Survey and the National Health Interview Survey both assess recent (i.e., in the past week or past month) habitual physical activity behaviors, including those performed during active travel. From these systems, the proportion of respondents who report any recent habitual active transportation can be calculated. The prevalence of active transportation as the primary commute mode to work in the past week ranged from 2.6% to 3.4%. The 1-day assessment indicated that the prevalence of any active transportation ranged from 10.5% to 18.5%. The prevalence of any habitual active transportation ranged from 23.9% to 31.4%. No consistent trends in active transportation across time periods and surveillance systems were identified. Among systems, active transportation was usually more common among men, younger respondents, and minority racial/ethnic groups. Among education groups, the highest prevalence of active transportation was usually among the least or most educated groups, and active transportation tended to be more

Cell swelling activates cloned Ca(2+)-activated K(+) channels: a role for the F-actin cytoskeleton

DEFF Research Database (Denmark)

Jorgensen, Nanna K; Pedersen, Stine F; Rasmussen, Hanne B

2003-01-01

Cloned Ca(2+)-activated K(+) channels of intermediate (hIK) or small (rSK3) conductance were expressed in HEK 293 cells, and channel activity was monitored using whole-cell patch clamp. hIK and rSK3 currents already activated by intracellular calcium were further increased by 95% and 125......%, respectively, upon exposure of the cells to a 33% decrease in extracellular osmolarity. hIK and rSK3 currents were inhibited by 46% and 32%, respectively, by a 50% increase in extracellular osmolarity. Cell swelling and channel activation were not associated with detectable increases in [Ca(2+)](i), evidenced...... by population and single-cell measurements. In addition, inhibitors of IK and SK channels significantly reduced the rate of regulatory volume decrease (RVD) in cells expressing these channels. Cell swelling induced a decrease, and cell shrinkage an increase, in net cellular F-actin content. The swelling...

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.

Regulation of cloned, Ca2+-activated K+ channels by cell volume changes

DEFF Research Database (Denmark)

Grunnet, Morten; MacAulay, Nanna; Jorgensen, Nanna K

2002-01-01

Ca2+-activated K+ channels of big (hBK), intermediate (hIK) or small (rSK3) conductance were co-expressed with aquaporin 1 (AQP1) in Xenopus laevis oocytes. hBK channels were activated by depolarization, whereas hIK and rSK3 channels were activated by direct injection of Ca2+ or Cd2+ into the ooc...

KCNQ4 channel activation by BMS-204352 and retigabine

DEFF Research Database (Denmark)

Schrøder, Rikke Louise K.; Jespersen, Thomas; Christophersen, P

2001-01-01

Activation of potassium channels generally reduces cellular excitability, making potassium channel openers potential drug candidates for the treatment of diseases related to hyperexcitabilty such as epilepsy, neuropathic pain, and neurodegeneration. Two compounds, BMS-204352 and retigabine, prese...

Hypoxic augmentation of Ca2+ channel currents requires a functional electron transport chain.

Science.gov (United States)

Brown, Stephen T; Scragg, Jason L; Boyle, John P; Hudasek, Kristin; Peers, Chris; Fearon, Ian M

2005-06-10

The incidence of Alzheimer disease is increased following ischemic episodes, and we previously demonstrated that following chronic hypoxia (CH), amyloid beta (Abeta) peptide-mediated increases in voltage-gated L-type Ca(2+) channel activity contribute to the Ca(2+) dyshomeostasis seen in Alzheimer disease. Because in certain cell types mitochondria are responsible for detecting altered O(2) levels we examined the role of mitochondrial oxidant production in the regulation of recombinant Ca(2+) channel alpha(1C) subunits during CH and exposure to Abeta-(1-40). In wild-type (rho(+)) HEK 293 cells expressing recombinant L-type alpha(1C) subunits, Ca(2+) currents were enhanced by prolonged (24 h) exposure to either CH (6% O(2)) or Abeta-(1-40) (50 nm). By contrast the response to CH was absent in rho(0) cells in which the mitochondrial electron transport chain (ETC) was depleted following long term treatment with ethidium bromide or in rho(+) cells cultured in the presence of 1 microm rotenone. CH was mimicked in rho(0) cells by the exogenous production of O2(-.). by xanthine/xanthine oxidase. Furthermore Abeta-(1-40) enhanced currents in rho(0) cells to a degree similar to that seen in cells with an intact ETC. The antioxidants ascorbate (200 microm) and Trolox (500 microm) ablated the effect of CH in rho(+) cells but were without effect on Abeta-(1-40)-mediated augmentation of Ca(2+) current in rho(0) cells. Thus oxidant production in the mitochondrial ETC is a critical factor, acting upstream of amyloid beta peptide production in the up-regulation of Ca(2+) channels in response to CH.

Size graded sediment dynamics: from the processes characterization to the transport modelling in the English Channel

International Nuclear Information System (INIS)

Blanpain, O.

2009-10-01

The purpose of this work is the implementation of a sediment transport model in the English Channel. The design of such a model requires the identification of the physical processes, their modelling and their in-situ validation. Because of the sedimentary particularities of the study area, modelling of the mechanical behaviour of a non uniform mixture of sediments and particularly of the fine grains within a coarse matrix is required. This study focused on the characterization of the relevant processes by acquisition of experimental and in-situ data. Data acquired in hydro-sedimentary conditions comparable to those found in the English Channel are scarce. A new instrument and image processing technique were specifically conceived and implemented in-situ to observe and measure, with a high temporal resolution, the dynamics of a strongly heterogeneous mixture of particles in a grain-size scale. The data collected compared well with several existing formulations. One of these formulations was chosen to be adapted. The transfer dynamics of fine grains in coarse sediments and their depth of penetration were acquired from stratigraphic samples. The sediment transport model deals with multi-size grains and multi sedimentary layers, it is forced by swell and currents, and accounts for bead load and suspended load transports. It was applied to realistic scenarios for the English Channel. (author)

Proteolytic activation of the epithelial sodium channel ENaC in preeclampsia examined with urinary exosomes

DEFF Research Database (Denmark)

Nielsen, Maria Ravn; Rytz, Mie; Frederiksen-Møller, Britta

2015-01-01

OBJECTIVES: Increased activity of the epithelial sodium channel (ENaC) in the kidneys may explain the coupling between proteinuria, edema, suppressed aldosterone and hypertension in preeclampsia. Preeclamptic women excrete plasminogen-plasmin in urine. In vitro, plasmin increases the activity...... as a positive control for the presence of collecting duct membrane. RESULTS: Urine plasmin-plasminogen/creatinine ratio was increased in the preeclampsia group (p... pregnancy and preeclampsia CONCLUSIONS: It is possible to examine collecting duct transport proteins in urine exosome from pregnant women including γ-ENaC, 2) Urine exosome fraction displays a variable pattern of γ-ENaC signal with a predominance of cleaved forms in both normal and preeclamptic women...

Fragile X mental retardation protein controls ion channel expression and activity.

Science.gov (United States)

Ferron, Laurent

2016-10-15

Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome, the most common cause of inherited intellectual disability and autism. FMRP is an RNA-binding protein involved in the control of local translation, which has pleiotropic effects, in particular on synaptic function. Analysis of the brain FMRP transcriptome has revealed hundreds of potential mRNA targets encoding postsynaptic and presynaptic proteins, including a number of ion channels. FMRP has been confirmed to bind voltage-gated potassium channels (K v 3.1 and K v 4.2) mRNAs and regulates their expression in somatodendritic compartments of neurons. Recent studies have uncovered a number of additional roles for FMRP besides RNA regulation. FMRP was shown to directly interact with, and modulate, a number of ion channel complexes. The sodium-activated potassium (Slack) channel was the first ion channel shown to directly interact with FMRP; this interaction alters the single-channel properties of the Slack channel. FMRP was also shown to interact with the auxiliary β4 subunit of the calcium-activated potassium (BK) channel; this interaction increases calcium-dependent activation of the BK channel. More recently, FMRP was shown to directly interact with the voltage-gated calcium channel, Ca v 2.2, and reduce its trafficking to the plasma membrane. Studies performed on animal models of fragile X syndrome have revealed links between modifications of ion channel activity and changes in neuronal excitability, suggesting that these modifications could contribute to the phenotypes observed in patients with fragile X-associated disorders. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Multi-Scale Thermal Heat Tracer Tests for Characterizing Transport Processes and Flow Channelling in Fractured Media: Theory and Field Experiments

Science.gov (United States)

de La Bernardie, J.; Klepikova, M.; Bour, O.; Le Borgne, T.; Dentz, M.; Guihéneuf, N.; Gerard, M. F.; Lavenant, N.

2017-12-01

The characterization of flow and transport in fractured media is particularly challenging because hydraulic conductivity and transport properties are often strongly dependent on the geometric structure of the fracture surfaces. Here we show how thermal tracer tests may be an excellent complement to conservative solute tracer tests to infer fracture geometry and flow channeling. We performed a series of thermal tracer tests at different scales in a crystalline rock aquifer at the experimental site of Ploemeur (H+ observatory network). The first type of thermal tracer tests are push-pull tracer tests at different scales. The temporal and spatial scaling of heat recovery, measured from thermal breakthrough curves, shows a clear signature of flow channeling. In particular, the late time tailing of heat recovery under channeled flow is shown to diverge from the T(t) α t-1,5 behavior expected for the classical parallel plate model and follow the scaling T(t) α 1/t(logt)2 for a simple channel modeled as a tube. Flow channeling is also manifested on the spatial scaling of heat recovery as flow channeling affects the decay of the thermal breakthrough peak amplitude and the increase of the peak time with scale. The second type of thermal tracer tests are flow-through tracer tests where a pulse of hot water was injected in a fracture isolated by a double straddle packer while pumping at the same flow rate in another fracture at a distance of about 10 meters to create a dipole flow field. Comparison with a solute tracer test performed under the same conditions also present a clear signature of flow channeling. We derive analytical expressions for the retardation and decay of the thermal breakthrough peak amplitude for different fracture geometries and show that the observed differences between thermal and solute breakthrough can be explained only by channelized flow. These results suggest that heat transport is much more sensitive to fracture heterogeneity and flow

Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle

Science.gov (United States)

Feng, Liang; Campbell, Ernest B.; Hsiung, Yichun; MacKinnon, Roderick

2011-01-01

CLC proteins transport Cl− ions across cell membranes to control the electrical potential of muscle cells, transfer electrolytes across epithelia, and control the pH and electrolyte composition of intracellular organelles. Some members of this protein family are Cl− ion channels, while others are secondary active transporters that exchange Cl− ions and H+ with a 2:1 stoichiometry. We have determined the structure of a eukaryotic CLC transporter at 3.5 Å resolution. Cytoplasmic CBS domains are strategically positioned to regulate the ion transport pathway, and many disease-causing mutations in human CLCs reside on the CBS-transmembrane interface. Comparison with prokaryotic CLC shows that a gating glutamate changes conformation and suggests a basis for 2:1 Cl−/H+ exchange and a simple mechanistic connection between CLC channels and transporters. PMID:20929736

Entropy production and rectification efficiency in colloid transport along a pulsating channel

Science.gov (United States)

Florencia Carusela, M.; Rubi, J. Miguel

2018-06-01

We study the current rectification of particles moving in a pulsating channel under the influence of an applied force. We have shown the existence of different rectification scenarios in which entropic and energetic effects compete. The effect can be quantified by means of a rectification coefficient that is analyzed in terms of the force, the frequency and the diffusion coefficient. The energetic cost of the motion of the particles expressed in terms of the entropy production depends on the importance of the entropic contribution to the total force. Rectification is more important at low values of the applied force when entropic effects become dominant. In this regime, the entropy production is not invariant under reversal of the applied force. The phenomenon observed could be used to optimize transport in microfluidic devices or in biological channels.

Estradiol rapidly induces the translocation and activation of the intermediate conductance calcium activated potassium channel in human eccrine sweat gland cells.

LENUS (Irish Health Repository)

Muchekehu, Ruth W

2009-02-01

Steroid hormones target K+ channels as a means of regulating electrolyte and fluid transport. In this study, ion transporter targets of Estradiol (E2) were investigated in the human eccrine sweat gland cell line NCL-SG3.

Alluvial cover controlling the width, slope and sinuosity of bedrock channels

Science.gov (United States)

Turowski, Jens Martin

2018-02-01

Bedrock channel slope and width are important parameters for setting bedload transport capacity and for stream-profile inversion to obtain tectonics information. Channel width and slope development are closely related to the problem of bedrock channel sinuosity. It is therefore likely that observations on bedrock channel meandering yields insights into the development of channel width and slope. Active meandering occurs when the bedrock channel walls are eroded, which also drives channel widening. Further, for a given drop in elevation, the more sinuous a channel is, the lower is its channel bed slope in comparison to a straight channel. It can thus be expected that studies of bedrock channel meandering give insights into width and slope adjustment and vice versa. The mechanisms by which bedrock channels actively meander have been debated since the beginning of modern geomorphic research in the 19th century, but a final consensus has not been reached. It has long been argued that whether a bedrock channel meanders actively or not is determined by the availability of sediment relative to transport capacity, a notion that has also been demonstrated in laboratory experiments. Here, this idea is taken up by postulating that the rate of change of both width and sinuosity over time is dependent on bed cover only. Based on the physics of erosion by bedload impacts, a scaling argument is developed to link bedrock channel width, slope and sinuosity to sediment supply, discharge and erodibility. This simple model built on sediment-flux-driven bedrock erosion concepts yields the observed scaling relationships of channel width and slope with discharge and erosion rate. Further, it explains why sinuosity evolves to a steady-state value and predicts the observed relations between sinuosity, erodibility and storm frequency, as has been observed for meandering bedrock rivers on Pacific Arc islands.

Alluvial cover controlling the width, slope and sinuosity of bedrock channels

Directory of Open Access Journals (Sweden)

J. M. Turowski

2018-02-01

Full Text Available Bedrock channel slope and width are important parameters for setting bedload transport capacity and for stream-profile inversion to obtain tectonics information. Channel width and slope development are closely related to the problem of bedrock channel sinuosity. It is therefore likely that observations on bedrock channel meandering yields insights into the development of channel width and slope. Active meandering occurs when the bedrock channel walls are eroded, which also drives channel widening. Further, for a given drop in elevation, the more sinuous a channel is, the lower is its channel bed slope in comparison to a straight channel. It can thus be expected that studies of bedrock channel meandering give insights into width and slope adjustment and vice versa. The mechanisms by which bedrock channels actively meander have been debated since the beginning of modern geomorphic research in the 19th century, but a final consensus has not been reached. It has long been argued that whether a bedrock channel meanders actively or not is determined by the availability of sediment relative to transport capacity, a notion that has also been demonstrated in laboratory experiments. Here, this idea is taken up by postulating that the rate of change of both width and sinuosity over time is dependent on bed cover only. Based on the physics of erosion by bedload impacts, a scaling argument is developed to link bedrock channel width, slope and sinuosity to sediment supply, discharge and erodibility. This simple model built on sediment-flux-driven bedrock erosion concepts yields the observed scaling relationships of channel width and slope with discharge and erosion rate. Further, it explains why sinuosity evolves to a steady-state value and predicts the observed relations between sinuosity, erodibility and storm frequency, as has been observed for meandering bedrock rivers on Pacific Arc islands.

Zinc-dependent multi-conductance channel activity in mitochondria isolated from ischemic brain.

Science.gov (United States)

Bonanni, Laura; Chachar, Mushtaque; Jover-Mengual, Teresa; Li, Hongmei; Jones, Adrienne; Yokota, Hidenori; Ofengeim, Dimitry; Flannery, Richard J; Miyawaki, Takahiro; Cho, Chang-Hoon; Polster, Brian M; Pypaert, Marc; Hardwick, J Marie; Sensi, Stefano L; Zukin, R Suzanne; Jonas, Elizabeth A

2006-06-21

Transient global ischemia is a neuronal insult that induces delayed cell death. A hallmark event in the early post-ischemic period is enhanced permeability of mitochondrial membranes. The precise mechanisms by which mitochondrial function is disrupted are, as yet, unclear. Here we show that global ischemia promotes alterations in mitochondrial membrane contact points, a rise in intramitochondrial Zn2+, and activation of large, multi-conductance channels in mitochondrial outer membranes by 1 h after insult. Mitochondrial channel activity was associated with enhanced protease activity and proteolytic cleavage of BCL-xL to generate its pro-death counterpart, deltaN-BCL-xL. The findings implicate deltaN-BCL-xL in large, multi-conductance channel activity. Consistent with this, large channel activity was mimicked by introduction of recombinant deltaN-BCL-xL to control mitochondria and blocked by introduction of a functional BCL-xL antibody to post-ischemic mitochondria via the patch pipette. Channel activity was also inhibited by nicotinamide adenine dinucleotide, indicative of a role for the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. In vivo administration of the membrane-impermeant Zn2+ chelator CaEDTA before ischemia or in vitro application of the membrane-permeant Zn2+ chelator tetrakis-(2-pyridylmethyl) ethylenediamine attenuated channel activity, suggesting a requirement for Zn2+. These findings reveal a novel mechanism by which ischemic insults disrupt the functional integrity of the outer mitochondrial membrane and implicate deltaN-BCL-xL and VDAC in the large, Zn2+-dependent mitochondrial channels observed in post-ischemic hippocampal mitochondria.

SENSITIVE EFFECTS OF POTASSIUM AND CALCIUM CHANNEL BLOCKING AND ATP-SENSITIVE POTASSIUM CHANNEL ACTIVATORS ON SEMINAL VESICLE SMOOTH MUSCLE CONTRACTIONS

Directory of Open Access Journals (Sweden)

H SADRAEI

2000-12-01

Full Text Available Background. Seminal vesicle smooth muscle contraction is mediated through sympathetic and parasympathetic neurons activity. Although seminal vesicle plays an important role in male fertility, but little attention is given to mechanism involved in contraction of this organ.
Methods. In this study effects of drugs which activate ATP - sensitive K channels and blockers of K and Ca channels were examined on contraction of guinea - pig isolated seminal vesicle due to electrical filled stimulation (EFS, noradrenaline, carbachol and KCI.
Results. The K channel blocker tetraethyl ammonium potentate the EFS responses at all frequencies, while, the ATP - sensitive K channel inhibitor glibenclamide and the K channel opener levcromakalim, diazoxide, minoxidil and Ca channel blocker nifedipine all had relaxant effect on guinea - pig seminal vesicle.
Discussion. This study indicate that activities of K and Ca channels is important in regulation of seminal vesicle contraction due to nerve stimulation, noradrenaline or carbachol.

Tasks related to increase of RA reactor exploitation and experimental potential, 04. Device for transport of radioactive reactor channels and semi channels of the RA reactor, design project (I-III) Part II, Vol. II; Radovi na povecanju eksploatacionih i eksperimentalnih mogucnosti reaktora RA, 04. Uredjaj za transport aktivnih tehnoloskih kanala I semikanala reaktora RA - izrada projekta (I-III), II Deo, Album II

Energy Technology Data Exchange (ETDEWEB)

Pavicevic, M [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1963-07-15

This second volume includes calculations of the main components of the transporter, description of the mechanical part of the transporter and the engineering drawing of the device for transport of radioactive reactor channels and semi channels of the RA reactor.

Nonlinear concentration gradients regulated by the width of channels for observation of half maximal inhibitory concentration (IC50) of transporter proteins.

Science.gov (United States)

Abe, Yuta; Kamiya, Koki; Osaki, Toshihisa; Sasaki, Hirotaka; Kawano, Ryuji; Miki, Norihisa; Takeuchi, Shoji

2015-08-21

This paper describes a simple microfluidic device that can generate nonlinear concentration gradients. We changed the "width" of channels that can drastically shorten the total microfluidic channel length and simplify the microfluidic network design rather than the "length" of channels. The logarithmic concentration gradients generated by the device were in good agreement with those obtained by simulation. Using this device, we evaluated a probable IC50 value of the ABC transporter proteins by the competitive transport assays at five different logarithmic concentrations. This probable IC50 value was in good agreement with an IC50 value (0.92 μM) obtained at the diluted concentrations of seven points.

Cytosolic nucleotides block and regulate the Arabidopsis vacuolar anion channel AtALMT9.

Science.gov (United States)

Zhang, Jingbo; Martinoia, Enrico; De Angeli, Alexis

2014-09-12

The aluminum-activated malate transporters (ALMTs) form a membrane protein family exhibiting different physiological roles in plants, varying from conferring tolerance to environmental Al(3+) to the regulation of stomatal movement. The regulation of the anion channels of the ALMT family is largely unknown. Identifying intracellular modulators of the activity of anion channels is fundamental to understanding their physiological functions. In this study we investigated the role of cytosolic nucleotides in regulating the activity of the vacuolar anion channel AtALMT9. We found that cytosolic nucleotides modulate the transport activity of AtALMT9. This modulation was based on a direct block of the pore of the channel at negative membrane potentials (open channel block) by the nucleotide and not by a phosphorylation mechanism. The block by nucleotides of AtALMT9-mediated currents was voltage dependent. The blocking efficiency of intracellular nucleotides increased with the number of phosphate groups and ATP was the most effective cellular blocker. Interestingly, the ATP block induced a marked modification of the current-voltage characteristic of AtALMT9. In addition, increased concentrations of vacuolar anions were able to shift the ATP block threshold to a more negative membrane potential. The block of AtALMT9-mediated anion currents by ATP at negative membrane potentials acts as a gate of the channel and vacuolar anion tune this gating mechanism. Our results suggest that anion transport across the vacuolar membrane in plant cells is controlled by cytosolic nucleotides and the energetic status of the cell. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Cytosolic Nucleotides Block and Regulate the Arabidopsis Vacuolar Anion Channel AtALMT9*

Science.gov (United States)

Zhang, Jingbo; Martinoia, Enrico; De Angeli, Alexis

2014-01-01

The aluminum-activated malate transporters (ALMTs) form a membrane protein family exhibiting different physiological roles in plants, varying from conferring tolerance to environmental Al3+ to the regulation of stomatal movement. The regulation of the anion channels of the ALMT family is largely unknown. Identifying intracellular modulators of the activity of anion channels is fundamental to understanding their physiological functions. In this study we investigated the role of cytosolic nucleotides in regulating the activity of the vacuolar anion channel AtALMT9. We found that cytosolic nucleotides modulate the transport activity of AtALMT9. This modulation was based on a direct block of the pore of the channel at negative membrane potentials (open channel block) by the nucleotide and not by a phosphorylation mechanism. The block by nucleotides of AtALMT9-mediated currents was voltage dependent. The blocking efficiency of intracellular nucleotides increased with the number of phosphate groups and ATP was the most effective cellular blocker. Interestingly, the ATP block induced a marked modification of the current-voltage characteristic of AtALMT9. In addition, increased concentrations of vacuolar anions were able to shift the ATP block threshold to a more negative membrane potential. The block of AtALMT9-mediated anion currents by ATP at negative membrane potentials acts as a gate of the channel and vacuolar anion tune this gating mechanism. Our results suggest that anion transport across the vacuolar membrane in plant cells is controlled by cytosolic nucleotides and the energetic status of the cell. PMID:25028514

Chlorovirus-mediated membrane depolarization of Chlorella alters secondary active transport of solutes.

Science.gov (United States)

Agarkova, Irina; Dunigan, David; Gurnon, James; Greiner, Timo; Barres, Julia; Thiel, Gerhard; Van Etten, James L

2008-12-01

Paramecium bursaria chlorella virus 1 (PBCV-1) is the prototype of a family of large, double-stranded DNA, plaque-forming viruses that infect certain eukaryotic chlorella-like green algae from the genus Chlorovirus. PBCV-1 infection results in rapid host membrane depolarization and potassium ion release. One interesting feature of certain chloroviruses is that they code for functional potassium ion-selective channel proteins (Kcv) that are considered responsible for the host membrane depolarization and, as a consequence, the efflux of potassium ions. This report examines the relationship between cellular depolarization and solute uptake. Annotation of the virus host Chlorella strain NC64A genome revealed 482 putative transporter-encoding genes; 224 are secondary active transporters. Solute uptake experiments using seven radioactive compounds revealed that virus infection alters the transport of all the solutes. However, the degree of inhibition varied depending on the solute. Experiments with nystatin, a drug known to depolarize cell membranes, produced changes in solute uptake that are similar but not identical to those that occurred during virus infection. Therefore, these studies indicate that chlorovirus infection causes a rapid and sustained depolarization of the host plasma membrane and that this depolarization leads to the inhibition of secondary active transporters that changes solute uptake.

Flowchart on Choosing Optimal Method of Observing Transverse Dispersion Coefficient for Solute Transport in Open Channel Flow

Directory of Open Access Journals (Sweden)

Kyong Oh Baek

2018-04-01

Full Text Available There are a number of methods for observing and estimating the transverse dispersion coefficient in an analysis of the solute transport in open channel flow. It may be difficult to select an optimal method to calculate dispersion coefficients from tracer data among numerous methodologies. A flowchart was proposed in this study to select an appropriate method under the transport situation of either time-variant or steady condition. When making the flowchart, the strengths and limitations of the methods were evaluated based on its derivation procedure which was conducted under specific assumptions. Additionally, application examples of these methods on experimental data were illustrated using previous works. Furthermore, the observed dispersion coefficients in a laboratory channel were validated by using transport numerical modeling, and the simulation results were compared with the experimental results from tracer tests. This flowchart may assist in choosing the better methods for determining the transverse dispersion coefficient in various river mixing situations.

Transport of sediment through a channel network during a post-fire debris flow

Science.gov (United States)

Nyman, P.; Box, W. A. C.; Langhans, C.; Stout, J. C.; Keesstra, S.; Sheridan, G. J.

2017-12-01

Transport processes linking sediment in steep headwaters with rivers during high magnitude events are rarely examined in detail, particularly in forested settings where major erosion events are rare and opportunities for collecting data are limited. Yet high magnitude events in headwaters are known to drive landscape change. This study examines how a debris flow after wildfire impacts on sediment transport from small headwaters (0.02 km2) through a step pool stream system within a larger 14 km2 catchment, which drains into the East Ovens River in SE Australia. Sediment delivery from debris flows was modelled and downstream deposition of sediment was measured using a combination of aerial imagery and field surveys. Particle size distributions were measured for all major deposits. These data were summarised to map sediment flux as a continuous variable over the drainage network. Total deposition throughout the stream network was 39 x 103 m3. Catchment efflux was 61 x 103 m3 (specific sediment yield of 78 ton ha-1), which equates to 400-800 years of background erosion, based on measurements in nearby catchments. Despite the low gradient (ca. 0.1 m m-1) of the main channel there was no systematic downstream sorting in sediment deposits in the catchment. This is due to debris flow processes operating throughout the stream network, with lateral inputs sustaining the process in low gradient channels, except in the most downstream reaches where the flow transitioned towards hyper-concentrated flow. Overall, a large proportion ( 88%) of the eroded fine fraction (<63 micron) exited the catchment, when compared to the overall ratio (55%) of erosion to deposition. The geomorphic legacy of this post-wildfire event depends on scale. In the lower channels (steam order 4-5), where erosion was nearly equal to deposition, the event had no real impact on total sediment volumes stored. In upper channels (stream orders < 3) erosion was widespread but deposition rates were low. So

Enhanced long-distance transport of periodic electron beams in an advanced double layer cone-channel target

Directory of Open Access Journals (Sweden)

Yanling Ji

2018-02-01

Full Text Available An enhanced long-distance transport of periodic electron beams in an advanced double layer cone-channel target is investigated using two-dimensional particle-in-cell simulations. The target consists of a cone attached to a double-layer hollow channel with a near-critical-density inner layer. The periodic electron beams are generated by the combination of ponderomotive force and longitudinal laser electric field. Then a stable electron propagation is achieved in the double-layer channel over a much longer distance without evident divergency, compared with a normal cone-channel target. Detailed simulations show that the much better long-distance collimation and guidance of energetic electrons is attributed to the much stronger electromagnetic fields at the inner wall surfaces. Furthermore, a continuous electron acceleration is obtained by the more intense laser electric fields and extended electron acceleration length in the channel. Our investigation shows that by employing this advanced target, both the forward-going electron energy flux in the channel and the energy coupling efficiency from laser to electrons are about threefold increased in comparison with the normal case.

Enhanced long-distance transport of periodic electron beams in an advanced double layer cone-channel target

Science.gov (United States)

Ji, Yanling; Duan, Tao; Zhou, Weimin; Li, Boyuan; Wu, Fengjuan; Zhang, Zhimeng; Ye, Bin; Wang, Rong; Wu, Chunrong; Tang, Yongjian

2018-02-01

An enhanced long-distance transport of periodic electron beams in an advanced double layer cone-channel target is investigated using two-dimensional particle-in-cell simulations. The target consists of a cone attached to a double-layer hollow channel with a near-critical-density inner layer. The periodic electron beams are generated by the combination of ponderomotive force and longitudinal laser electric field. Then a stable electron propagation is achieved in the double-layer channel over a much longer distance without evident divergency, compared with a normal cone-channel target. Detailed simulations show that the much better long-distance collimation and guidance of energetic electrons is attributed to the much stronger electromagnetic fields at the inner wall surfaces. Furthermore, a continuous electron acceleration is obtained by the more intense laser electric fields and extended electron acceleration length in the channel. Our investigation shows that by employing this advanced target, both the forward-going electron energy flux in the channel and the energy coupling efficiency from laser to electrons are about threefold increased in comparison with the normal case.

Structure of a Eukaryotic CLC Transporter Defines an Intermediate State in the Transport Cycle

International Nuclear Information System (INIS)

Feng, Liang; Campbell, Ernest B.; Hsiung, Yichun; MacKinnon, Roderick

2010-01-01

CLC proteins transport chloride (Cl - ) ions across cell membranes to control the electrical potential of muscle cells, transfer electrolytes across epithelia, and control the pH and electrolyte composition of intracellular organelles. Some members of this protein family are Cl - ion channels, whereas others are secondary active transporters that exchange Cl - ions and protons (H + ) with a 2:1 stoichiometry. We have determined the structure of a eukaryotic CLC transporter at 3.5 angstrom resolution. Cytoplasmic cystathionine beta-synthase (CBS) domains are strategically positioned to regulate the ion-transport pathway, and many disease-causing mutations in human CLCs reside on the CBS-transmembrane interface. Comparison with prokaryotic CLC shows that a gating glutamate residue changes conformation and suggests a basis for 2:1 Cl - /H + exchange and a simple mechanistic connection between CLC channels and transporters.

Turbulent transport of passive scalar behind line sources in an unstably stratified open channel flow

Energy Technology Data Exchange (ETDEWEB)

Liu, Chun-Ho [The Hong Kong Polytechnic University, Kowloon (Hong Kong). Department of Building and Real Estate; Leung, Dennis Y.C. [The University of Hong Kong (Hong Kong). Department of Mechanical Engineering

2006-11-15

This study employs a direct numerical simulation (DNS) technique to study the flow, turbulence structure, and passive scalar plume transport behind line sources in an unstably stratified open channel flow. The scalar transport behaviors for five emission heights (z{sub s}=0, 0.25H, 0.5H, 0.75H, and H, where H is the channel height) at a Reynolds number of 3000, a Prandtl number and a Schmidt number of 0.72, and a Richardson number of -0.2 are investigated. The vertically meandering mean plume heights and dispersion coefficients calculated by the current DNS model agree well with laboratory results and field measurements in literature. It is found that the plume meandering is due to the movement of the positive and negative vertical turbulent scalar fluxes above and below the mean plume heights, respectively. These findings help explaining the plume meandering mechanism in the unstably stratified atmospheric boundary layer. (author)

Light-induced modification of plant plasma membrane ion transport.

Science.gov (United States)

Marten, I; Deeken, R; Hedrich, R; Roelfsema, M R G

2010-09-01

Light is not only the driving force for electron and ion transport in the thylakoid membrane, but also regulates ion transport in various other membranes of plant cells. Light-dependent changes in ion transport at the plasma membrane and associated membrane potential changes have been studied intensively over the last century. These studies, with various species and cell types, revealed that apart from regulation by chloroplasts, plasma membrane transport can be controlled by phytochromes, phototropins or channel rhodopsins. In this review, we compare light-dependent plasma membrane responses of unicellular algae (Eremosphaera and Chlamydomonas), with those of a multicellular alga (Chara), liverworts (Conocephalum), mosses (Physcomitrella) and several angiosperm cell types. Light-dependent plasma membrane responses of Eremosphaera and Chara are characterised by the dominant role of K(+) channels during membrane potential changes. In most other species, the Ca(2+)-dependent activation of plasma membrane anion channels represents a general light-triggered event. Cell type-specific responses are likely to have evolved by modification of this general response or through the development of additional light-dependent signalling pathways. Future research to elucidate these light-activated signalling chains is likely to benefit from the recent identification of S-type anion channel genes and proteins capable of regulating these channels.

Hierarchically porous carbon with high-speed ion transport channels for high performance supercapacitors

Science.gov (United States)

Lu, Haoyuan; Li, Qingwei; Guo, Jianhui; Song, Aixin; Gong, Chunhong; Zhang, Jiwei; Zhang, Jingwei

2018-01-01

Hierarchically porous carbons (HPC) are considered as promising electrode materials for supercapacitors, due to their outstanding charge/discharge cycling stabilities and high power densities. However, HPC possess a relatively low ion diffusion rate inside the materials, which challenges their application for high performance supercapacitor. Thus tunnel-shaped carbon pores with a size of tens of nanometers were constructed by inducing the self-assembly of lithocholic acid with ammonium chloride, thereby providing high-speed channels for internal ion diffusion. The as-formed one-dimensional pores are beneficial to the activation process by KOH, providing a large specific surface area, and then facilitate rapid transport of electrolyte ions from macropores to the microporous surfaces. Therefore, the HPC achieve an outstanding gravimetric capacitance of 284 F g-1 at a current density of 0.1 A g-1 and a remarkable capacity retention of 64.8% when the current density increases by 1000 times to 100 A g-1.

First demonstration of single-mode MCF transport network with crosstalk-aware in-service optical channel control

DEFF Research Database (Denmark)

Pulverer, K.; Tanaka, T.; Häbel, U.

2017-01-01

We demonstrate the first crosstalk-aware traffic engineering as a use case in a multicore fibre transport network. With the help of a software-defined network controller, modulation format and channel route are adaptively changed using programmable devices with XT monitors....

Studies of heavy ion beam transport in a magnetic quadrupole channel

International Nuclear Information System (INIS)

Klabunde, J.; Reiser, M.; Schonlein, A.; Spadtke, P.; Struckmeier, J.

1983-01-01

In connection with the West German Heavy Ion Fusion Program the first stage (six periods) of a magnetic quadrupole channel (FODO type) to study the transport of intense ion beams was built at GSI. Different ion beams can be used and the variation of the brightness of these beams (hence of the tune depression sigma/sigma /SUB o/ ) is sufficiently large that regions of theoretically predicted instabilities can be covered. The initial studies are being carried out with a high-brightness beam of 190 keV Ar+ ions and currents of a few mA. Since the pulse length is > 0.5 ms and the pressure is between 10 -6 and 10 -7 torr partial space charge neutralization occurs. Clearing electrodes can be used to remove the electrons from the beam. Results of theoretical studies, measurements of charge neutralization effects and first results of transport experiments are reported

A new scripting library for modeling flow and transport in fractured rock with channel networks

Science.gov (United States)

Dessirier, Benoît; Tsang, Chin-Fu; Niemi, Auli

2018-02-01

Deep crystalline bedrock formations are targeted to host spent nuclear fuel owing to their overall low permeability. They are however highly heterogeneous and only a few preferential paths pertaining to a small set of dominant rock fractures usually carry most of the flow or mass fluxes, a behavior known as channeling that needs to be accounted for in the performance assessment of repositories. Channel network models have been developed and used to investigate the effect of channeling. They are usually simpler than discrete fracture networks based on rock fracture mappings and rely on idealized full or sparsely populated lattices of channels. This study reexamines the fundamental parameter structure required to describe a channel network in terms of groundwater flow and solute transport, leading to an extended description suitable for unstructured arbitrary networks of channels. An implementation of this formalism in a Python scripting library is presented and released along with this article. A new algebraic multigrid preconditioner delivers a significant speedup in the flow solution step compared to previous channel network codes. 3D visualization is readily available for verification and interpretation of the results by exporting the results to an open and free dedicated software. The new code is applied to three example cases to verify its results on full uncorrelated lattices of channels, sparsely populated percolation lattices and to exemplify the use of unstructured networks to accommodate knowledge on local rock fractures.

Flow and sediment transport across oblique channels

DEFF Research Database (Denmark)

Hjelmager Jensen, Jacob; Madsen, Erik Østergaard; Fredsøe, Jørgen

1998-01-01

A 3D numerical investigation of flow across channels aligned obliquely to the main flow direction has been conducted. The applied numerical model solves the Reynolds-averaged Navier-Stokes equations using the k-ε model for turbulence closure on a curvilinear grid. Three momentum equations...... are solved, but the computational domain is 2D due to a uniformity along the channel alignment. Two important flow features arise when the flow crosses the channel: (i) the flow will be refracted in the direction of the channel alignment. This may be described by a depth-averaged model. (ii) due to shear...

Design studies of an electrostatic quadrupole channel for transport of a high-brightness H- beam and comparison with gas focusing

International Nuclear Information System (INIS)

Chang, C.R.; Horowitz, E.; Reiser, M.

1989-01-01

Transport of low-energy, high-brightness H - beams from the ion source to the radio-frequency quadrupole (RFQ) accelerator requires the solution of several physics and engineering problems to avoid particle losses and emittance growth. The authors developed a conceptual design of an electrostatic quadrupole channel for transport of a 120 keV, 120 mA, H - beam into a 425 MHz RFQ with low emittance growth and high transmission efficiency. This design satisfies several constraints imposed by voltage breakdown and beam optics considerations. The system will consist entirely of electrostatic lenses which prevent plasma build-up and eliminate possible emittance growth from plasma fluctuations. Pertinent design features a worst case non-linear analysis for the electrostatic quadrupole channel, and first results of a particle simulation code used to study beam loss and emittance growth are reported. As an alternative to the electrostatic quadrupole concept, gas focusing is being investigated for transporting low-energy H - beams. Recent results from the numerical simulations of such a gas focussing channel are presented

Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate.

Science.gov (United States)

Gao, Haixia; Boillat, Aurélien; Huang, Dongyang; Liang, Ce; Peers, Chris; Gamper, Nikita

2017-08-01

M-type (Kv7, KCNQ) potassium channels are proteins that control the excitability of neurons and muscle cells. Many physiological and pathological mechanisms of excitation operate via the suppression of M channel activity or expression. Conversely, pharmacological augmentation of M channel activity is a recognized strategy for the treatment of hyperexcitability disorders such as pain and epilepsy. However, physiological mechanisms resulting in M channel potentiation are rare. Here we report that intracellular free zinc directly and reversibly augments the activity of recombinant and native M channels. This effect is mechanistically distinct from the known redox-dependent KCNQ channel potentiation. Interestingly, the effect of zinc cannot be attributed to a single histidine- or cysteine-containing zinc-binding site within KCNQ channels. Instead, zinc dramatically reduces KCNQ channel dependence on its obligatory physiological activator, phosphatidylinositol 4,5-bisphosphate (PIP 2 ). We hypothesize that zinc facilitates interactions of the lipid-facing interface of a KCNQ protein with the inner leaflet of the plasma membrane in a way similar to that promoted by PIP 2 Because zinc is increasingly recognized as a ubiquitous intracellular second messenger, this discovery might represent a hitherto unknown native pathway of M channel modulation and provide a fresh strategy for the design of M channel activators for therapeutic purposes.

Plasma lens focusing and plasma channel transport for heavy ion fusion

International Nuclear Information System (INIS)

Tauschwitz, A.; Yu, S.S.; Bangerter, R.O.

1996-01-01

The final focus lens in an ion beam driven inertial confinement fusion reactor is important since it sets limiting requirements for the quality of the driver beam. Improvements of the focusing capabilities can facilitate the construction of the driver significantly. A focusing system that is of interest both for heavy ion and for light ion drivers is an adiabatic, current carrying plasma lens. This lens is characterized by the fact that it can slowly (adiabatically) reduce the envelope radius of a beam over several betatron oscillations by increasing the focusing magnetic field along a tapered high current discharge. A reduction of the beam diameter by a factor of 3 to 5 seems feasible with this focusing scheme. Such a lens can be used for an ignition test facility where it can be directly coupled to the fusion target. For use in a repetitively working reactor chamber the lens has to be located outside of the reactor and the tightly focused but strongly divergent beam must be confined in a high current transport channel from the end of the lens into the immediate vicinity of the target. Laser preionization of a background gas is an efficient means to direct and stabilize such a channel. Experiments have been started to test both, the principle of adiabatic focusing, and the stability of laser preionized high current discharge channels. (author). 4 figs., 7 refs

Plasma lens focusing and plasma channel transport for heavy ion fusion

Energy Technology Data Exchange (ETDEWEB)

Tauschwitz, A; Yu, S S; Bangerter, R O [Lawrence Berkeley Lab., CA (United States); and others

1997-12-31

The final focus lens in an ion beam driven inertial confinement fusion reactor is important since it sets limiting requirements for the quality of the driver beam. Improvements of the focusing capabilities can facilitate the construction of the driver significantly. A focusing system that is of interest both for heavy ion and for light ion drivers is an adiabatic, current carrying plasma lens. This lens is characterized by the fact that it can slowly (adiabatically) reduce the envelope radius of a beam over several betatron oscillations by increasing the focusing magnetic field along a tapered high current discharge. A reduction of the beam diameter by a factor of 3 to 5 seems feasible with this focusing scheme. Such a lens can be used for an ignition test facility where it can be directly coupled to the fusion target. For use in a repetitively working reactor chamber the lens has to be located outside of the reactor and the tightly focused but strongly divergent beam must be confined in a high current transport channel from the end of the lens into the immediate vicinity of the target. Laser preionization of a background gas is an efficient means to direct and stabilize such a channel. Experiments have been started to test both, the principle of adiabatic focusing, and the stability of laser preionized high current discharge channels. (author). 4 figs., 7 refs.

Transport on prescription: How can GPs contribute to the promotion of active transport?

Science.gov (United States)

Pistoll, Chance; Furler, John

2017-10-01

Active transport (ie walking, cycling, using public transport) can play a part in reducing non-communicable diseases (NCDs). Very little is known about how general practitioners (GPs) can contribute to promoting active transport. We explored GPs' ideas around active transport, and potential barriers and facilitators to its promotion in the clinical setting. Using a maximal variation sample, we conducted 10 semi-structured interviews with GPs in Victoria, Australia. The socioecological model informed data collection and analysis. The idea of active transport resonated with GPs. Limited awareness around active transport and safety concerns regarding commuter cycling were barriers to clinical promotion. GPs believed patients' health, cultural norms, socioeconomic position and access to supportive environments could facilitate participation. Future efforts should prioritise awareness of active transport among GPs. The perspectives of GPs would be valuable to policymakers, particularly in designing programs to mitigate inequalities around active transport access and use.

Highly selective water channel activity measured by voltage clamp: analysis of planar lipid bilayers reconstituted with purified AqpZ.

Science.gov (United States)

Pohl, P; Saparov, S M; Borgnia, M J; Agre, P

2001-08-14

Aquaporins are membrane channels selectively permeated by water or water plus glycerol. Conflicting reports have described ion conductance associated with some water channels, raising the question of whether ion conductance is a general property of the aquaporin family. To clarify this question, a defined system was developed to simultaneously measure water permeability and ion conductance. The Escherichia coli water channel aquaporin-Z (AqpZ) was studied, because it is a highly stable tetramer. Planar lipid bilayers were formed from unilamellar vesicles containing purified AqpZ. The hydraulic conductivity of bilayers made from the total extract of E. coli lipids increased 3-fold if reconstituted with AqpZ, but electric conductance was unchanged. No channel activity was detected under voltage-clamp conditions, indicating that less than one in 10(9) transport events is electrogenic. Microelectrode measurements were simultaneously undertaken adjacent to the membrane. Changes in sodium concentration profiles accompanying transmembrane water flow permitted calculation of the activation energies: 14 kcal/mol for protein-free lipid bilayers and 4 kcal/mol for lipid bilayers containing AqpZ. Neither the water permeability nor the electric conductivity exhibited voltage dependence. This sensitive system demonstrated that AqpZ is permeated by water but not charged ions and should permit direct analyses of putative electrogenic properties of other aquaporins.

[G-protein potentiates the activation of TNF-alpha on calcium-activated potassium channel in ECV304].

Science.gov (United States)

Lin, L; Zheng, Y; Qu, J; Bao, G

2000-06-01

Observe the effect of tumor necrosis factor-alpha (TNF-alpha) on calcium-activated potassium channel in ECV304 and the possible involvement of G-protein mediation in the action of TNF-alpha. Using the cell-attached configuration of patch clamp technique. (1) the activity of high-conductance calcium-activated potassium channel (BKca) was recorded. Its conductance is (202.54 +/- 16.62) pS; (2) the activity of BKca was potentiated by 200 U/ml TNF-alpha; (3) G-protein would intensify this TNF-alpha activation. TNF-alpha acted on vascular endothelial cell ECV304 could rapidly activate the activity of BKca. Opening of BKca resulted in membrane hyper-polarization which could increase electro-chemical gradient for the resting Ca2+ influx and open leakage calcium channel, thus resting cytoplasmic free Ca2+ concentration could be elevated. G-protein may exert an important regulation in this process.

Imaging large cohorts of single ion channels and their activity

Directory of Open Access Journals (Sweden)

Katia eHiersemenzel

2013-09-01

Full Text Available As calcium is the most important signaling molecule in neurons and secretory cells, amongst many other cell types, it follows that an understanding of calcium channels and their regulation of exocytosis is of vital importance. Calcium imaging using calcium dyes such as Fluo3, or FRET-based dyes that have been used widely has provided invaluable information, which combined with modeling has estimated the sub-types of channels responsible for triggering the exocytotic machinery as well as inferences about the relative distances away from vesicle fusion sites these molecules adopt. Importantly, new super-resolution microscopy techniques, combined with novel Ca2+ indicators and imaginative imaging approaches can now define directly the nanoscale locations of very large cohorts of single channel molecules in relation to single vesicles. With combinations of these techniques the activity of individual channels can be visualized and quantified using novel Ca2+ indicators. Fluorescently labeled specific channel toxins can also be used to localize endogenous assembled channel tetramers. Fluorescence lifetime imaging microscopy and other single-photon-resolution spectroscopic approaches offer the possibility to quantify protein-protein interactions between populations of channels and the SNARE protein machinery for the first time. Together with simultaneous electrophysiology, this battery of quantitative imaging techniques has the potential to provide unprecedented detail describing the locations, dynamic behaviours, interactions and conductance activities of many thousands of channel molecules and vesicles in living cells.

Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na+/K+-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes

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Stefanie Klinger

2018-03-01

Full Text Available Background: Beneficial effects of Resveratrol (RSV have been demonstrated, including effects on transporters and channels. However, little is known about how RSV influences intestinal transport. The aim of this study was to further characterize the effects of RSV on intestinal transport and the respective mechanisms. Methods: Porcine jejunum and ileum were incubated with RSV (300 µM, 30 min in Ussing chambers (functional studies and tissue bathes (detection of protein expression, phosphorylation, association with detergent resistant membranes (DRMs. Results: RSV reduced alanine and glucose-induced short circuit currents (ΔIsc and influenced forskolin-induced ΔIsc. The phosphorylation of sodium–glucose-linked transporter 1 (SGLT1, AMP-activated protein kinase (AMPK, protein kinase A substrates (PKA-S and liver kinase B1 (LKB1 increased but a causative relation to the inhibitory effects could not directly be established. The DRM association of SGLT1, peptide transporter 1 (PEPT1 and (phosphorylated Na+/H+-exchanger 3 (NHE3 did not change. Conclusion: RSV influences the intestinal transport of glucose, alanine and chloride and is likely to affect other transport processes. As the effects of protein kinase activation vary between the intestinal localizations, it would appear that increasing cyclic adenosine monophosphate (cAMP levels are part of the mechanism. Nonetheless, the physiological responses depend on cell type-specific structures.

Genetic disorders of transporters/channels in the inner ear and their relation to the kidney.

NARCIS (Netherlands)

Peters, T.A.; Monnens, L.A.H.; Cremers, C.W.R.J.; Curfs, J.H.A.J.

2004-01-01

Inner ear physiology is reviewed with emphasis on features common to renal physiology. Genetic disorders in transporters/channels for chloride (ClC-K), bicarbonate (Cl(-)/HCO(3)(-) exchanger), protons (H(+)-ATPase), sodium (ENaC, NKKC1, NBC3, NHE3), potassium (KCNQ1/KCNE1, Kcc4), and water (AQP4) in

The temperature dependence of the BK channel activity - kinetics, thermodynamics, and long-range correlations.

Science.gov (United States)

Wawrzkiewicz-Jałowiecka, Agata; Dworakowska, Beata; Grzywna, Zbigniew J

2017-10-01

Large-conductance, voltage dependent, Ca 2+ -activated potassium channels (BK) are transmembrane proteins that regulate many biological processes by controlling potassium flow across cell membranes. Here, we investigate to what extent temperature (in the range of 17-37°C with ΔT=5°C step) is a regulating parameter of kinetic properties of the channel gating and memory effect in the series of dwell-time series of subsequent channel's states, at membrane depolarization and hyperpolarization. The obtained results indicate that temperature affects strongly the BK channels' gating, but, counterintuitively, it exerts no effect on the long-range correlations, as measured by the Hurst coefficient. Quantitative differences between dependencies of appropriate channel's characteristics on temperature are evident for different regimes of voltage. Examining the characteristics of BK channel activity as a function of temperature allows to estimate the net activation energy (E act ) and changes of thermodynamic parameters (ΔH, ΔS, ΔG) by channel opening. Larger E act corresponds to the channel activity at membrane hyperpolarization. The analysis of entropy and enthalpy changes of closed to open channel's transition suggest the entropy-driven nature of the increase of open state probability during voltage activation and supports the hypothesis about the voltage-dependent geometry of the channel vestibule. Copyright © 2017 Elsevier B.V. All rights reserved.

Unique battery with an active membrane separator having uniform physico-chemically functionalized ion channels and a method making the same

Science.gov (United States)

Gerald, II, Rex E.; Ruscic, Katarina J [Chicago, IL; Sears, Devin N [Spruce Grove, CA; Smith, Luis J [Natick, MA; Klingler, Robert J [Glenview, IL; Rathke, Jerome W [Homer Glen, IL

2012-02-21

The invention relates to a unique battery having an active, porous membrane and method of making the same. More specifically the invention relates to a sealed battery system having a porous, metal oxide membrane with uniform, physicochemically functionalized ion channels capable of adjustable ionic interaction. The physicochemically-active porous membrane purports dual functions: an electronic insulator (separator) and a unidirectional ion-transporter (electrolyte). The electrochemical cell membrane is activated for the transport of ions by contiguous ion coordination sites on the interior two-dimensional surfaces of the trans-membrane unidirectional pores. The membrane material is designed to have physicochemical interaction with ions. Control of the extent of the interactions between the ions and the interior pore walls of the membrane and other materials, chemicals, or structures contained within the pores provides adjustability of the ionic conductivity of the membrane.

Charge and spin transport in edge channels of a ν=0 quantum Hall system on the surface of topological insulators.

Science.gov (United States)

Morimoto, Takahiro; Furusaki, Akira; Nagaosa, Naoto

2015-04-10

Three-dimensional topological insulators of finite thickness can show the quantum Hall effect (QHE) at the filling factor ν=0 under an external magnetic field if there is a finite potential difference between the top and bottom surfaces. We calculate energy spectra of surface Weyl fermions in the ν=0 QHE and find that gapped edge states with helical spin structure are formed from Weyl fermions on the side surfaces under certain conditions. These edge channels account for the nonlocal charge transport in the ν=0 QHE which is observed in a recent experiment on (Bi_{1-x}Sb_{x})_{2}Te_{3} films. The edge channels also support spin transport due to the spin-momentum locking. We propose an experimental setup to observe various spintronics functions such as spin transport and spin conversion.

Multiple-channel detection of cellular activities by ion-sensitive transistors

Science.gov (United States)

Machida, Satoru; Shimada, Hideto; Motoyama, Yumi

2018-04-01

An ion-sensitive field-effect transistor to record cellular activities was demonstrated. This field-effect transistor (bio transistor) includes cultured cells on the gate insulator instead of gate electrode. The bio transistor converts a change in potential underneath the cells into variation of the drain current when ion channels open. The bio transistor has high detection sensitivity to even minute variations in potential utilizing a subthreshold swing region. To open ion channels, a reagent solution (acetylcholine) was added to a human-originating cell cultured on the bio transistor. The drain current was successfully decreased with the addition of acetylcholine. Moreover, we attempted to detect the opening of ion channels using a multiple-channel measurement circuit containing several bio transistors. As a consequence, the drain current distinctly decreased only after the addition of acetylcholine. We confirmed that this measurement system including bio transistors enables to observation of cellular activities sensitively and simultaneously.

Active transport among Czech school-aged children

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Jan Pavelka

2012-09-01

Full Text Available BACKGROUND: Active transport is a very important factor for increasing the level of physical activity in children, which is significant for both their health and positive physical behaviour in adult age. OBJECTIVE: The aim of the study was to establish the proportion of Czech children aged 11 to 15 who select active transport to and from school and, at the same time, describe socio-economic and socio-demographic factors influencing active transport to and from school among children. METHODS: To establish the socio-demographic factors affecting active transport, data of a national representative sample of 11 to 15 year-old elementary school children in the Czech Republic (n = 4,425. Research data collection was performed within an international research study called Health Behaviour in School Aged Children in June 2010. Statistical processing of the results was made using a logistic regression analysis in the statistical programme IBM SPSS v 20. RESULTS: Active transport to and from school is opted for in the Czech Republic by approximately 2/3 of children aged 11 to 15. Differences between genders are not statistically significant; most children opting for active transport are aged 11 (69%. An important factor increasing the probability of active transport as much as 16 times is whether a child's place of residence is in the same municipality as the school. Other factors influencing this choice include BMI, time spent using a computer or a privateroom in a family. A significant factor determining active transport by children is safety; safe road crossing, opportunity to leave a bicycle safely at school, no fear of being assaulted on the way or provision of school lockers where children can leave their items. CONCLUSIONS: Active transport plays an important role in increasing the overall level of physical activity in children. Promotion of active transport should focus on children who spend more time using a computer; attention should also be

Momentum and scalar transport in a localised synthetic turbulence in a channel flow with a short contraction

Energy Technology Data Exchange (ETDEWEB)

Lefeuvre, N; Djenidi, L [University of Newcastle, NSW Australia (Australia); Tardu, S, E-mail: nathan.lefeuvre@uon.edu.au [Laboratoire des Ecoulements Geophysiques et Industriels (LEGI), Grenoble (France)

2011-12-22

A numerical simulation is undertaken to investigate the transport of momentum and a passive scalar in a localised turbulence in a channel with a contraction. The simulation is carried out using a hybrid method which combines the lattice Boltzmann method (LBM, for the velocity field) and the energy equation (for the temperature field). The localised turbulence is generated through pulsed jets issued in the Poiseuille flow developing in the channel at a Reynolds number of about 1000. The aim of the study is twofold : i) determine effect of the contraction on the localised turbulence, and ii) study how the passive scalar behaves in such contracted localised turbulence. The contraction increase the averaged vorticity in the channel flow, which is accompanied by an increase in the averaged kinetic energy. The contraction also tends to reduce the Reynolds stresses. These results are similar those obtained in turbulent pipe flow with an axisymmetric contraction and in a turbulent boundary layer subjected to a favourable pressure gradient. However, it is found that the heat transport in the normal to the wall direction is more dramatically affected (reduced) than that in the direction of the flow.

Health Impacts of Active Transportation in Europe

DEFF Research Database (Denmark)

Rojas-Rueda, David; de Nazelle, Audrey; Andersen, Zorana J

2016-01-01

Policies that stimulate active transportation (walking and bicycling) have been related to heath benefits. This study aims to assess the potential health risks and benefits of promoting active transportation for commuting populations (age groups 16-64) in six European cities. We conducted a health...... reduce carbon dioxide emissions in the six cities by 1,139 to 26,423 (metric tonnes per year). Policies to promote active transportation may produce health benefits, but these depend of the existing characteristics of the cities. Increased collaboration between health practitioners, transport specialists...... and urban planners will help to introduce the health perspective in transport policies and promote active transportation....

Active transportation and public transportation use to achieve physical activity recommendations? A combined GPS, accelerometer, and mobility survey study.

Science.gov (United States)

Chaix, Basile; Kestens, Yan; Duncan, Scott; Merrien, Claire; Thierry, Benoît; Pannier, Bruno; Brondeel, Ruben; Lewin, Antoine; Karusisi, Noëlla; Perchoux, Camille; Thomas, Frédérique; Méline, Julie

2014-09-27

Accurate information is lacking on the extent of transportation as a source of physical activity, on the physical activity gains from public transportation use, and on the extent to which population shifts in the use of transportation modes could increase the percentage of people reaching official physical activity recommendations. In 2012-2013, 234 participants of the RECORD GPS Study (French Paris region, median age = 58) wore a portable GPS receiver and an accelerometer for 7 consecutive days and completed a 7-day GPS-based mobility survey (participation rate = 57.1%). Information on transportation modes and accelerometry data aggregated at the trip level [number of steps taken, energy expended, moderate to vigorous physical activity (MVPA), and sedentary time] were available for 7,644 trips. Associations between transportation modes and accelerometer-derived physical activity were estimated at the trip level with multilevel linear models. Participants spent a median of 1 h 58 min per day in transportation (8.2% of total time). Thirty-eight per-cent of steps taken, 31% of energy expended, and 33% of MVPA over 7 days were attributable to transportation. Walking and biking trips but also public transportation trips with all four transit modes examined were associated with greater steps, MVPA, and energy expenditure when compared to trips by personal motorized vehicle. Two simulated scenarios, implying a shift of approximately 14% and 33% of all motorized trips to public transportation or walking, were associated with a predicted 6 point and 13 point increase in the percentage of participants achieving the current physical activity recommendation. Collecting data with GPS receivers, accelerometers, and a GPS-based electronic mobility survey of activities and transportation modes allowed us to investigate relationships between transportation modes and physical activity at the trip level. Our findings suggest that an increase in active transportation

ACTIVITY THEORY APPLIED AT CHANNEL EXPANSIONS IN SMALL AND MEDIUM ENTERPRISES

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Siw Lundqvist

2017-06-01

Full Text Available Today’s commonly carried out channel expansions of commerce could be both costly and problematic to manage. Especially for small and medium-sized enterprises (SMEs that often suffer from a lack of digital competence, time and monetary resources in generally. Still, these transitions would be necessary to carry out because of customer demands and expectations concerning 24/7 availability, and access to digital commerce alternatives. Scarce resources are important reasons to search for how to carry out channel expansions with minimized problems. Activity theory (AT focuses on the whole in order to detect problems that hinder successful outcomes. Hence, this theory was applied to prior findings, from a project about SME’s channel expansions, highlighting several problems that could appear during these activities. Implications for research foremost involve issues connected to the use of AT; implications for practice particularly concern if and how AT could be used to support channel broadening activities.

Stretch-activated cation channel from larval bullfrog skin

DEFF Research Database (Denmark)

Hillyard, Stanley D; Willumsen, Niels J; Marrero, Mario B

2010-01-01

Cell-attached patches from isolated epithelial cells from larval bullfrog skin revealed a cation channel that was activated by applying suction (-1 kPa to -4.5 kPa) to the pipette. Activation was characterized by an initial large current spike that rapidly attenuated to a stable value and showed ...

The Role of Na+ and K+ Transporters in Salt Stress Adaptation in Glycophytes

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Dekoum V. M. Assaha

2017-07-01

Full Text Available Ionic stress is one of the most important components of salinity and is brought about by excess Na+ accumulation, especially in the aerial parts of plants. Since Na+ interferes with K+ homeostasis, and especially given its involvement in numerous metabolic processes, maintaining a balanced cytosolic Na+/K+ ratio has become a key salinity tolerance mechanism. Achieving this homeostatic balance requires the activity of Na+ and K+ transporters and/or channels. The mechanism of Na+ and K+ uptake and translocation in glycophytes and halophytes is essentially the same, but glycophytes are more susceptible to ionic stress than halophytes. The transport mechanisms involve Na+ and/or K+ transporters and channels as well as non-selective cation channels. Thus, the question arises of whether the difference in salt tolerance between glycophytes and halophytes could be the result of differences in the proteins or in the expression of genes coding the transporters. The aim of this review is to seek answers to this question by examining the role of major Na+ and K+ transporters and channels in Na+ and K+ uptake, translocation and intracellular homeostasis in glycophytes. It turns out that these transporters and channels are equally important for the adaptation of glycophytes as they are for halophytes, but differential gene expression, structural differences in the proteins (single nucleotide substitutions, impacting affinity and post-translational modifications (phosphorylation account for the differences in their activity and hence the differences in tolerance between the two groups. Furthermore, lack of the ability to maintain stable plasma membrane (PM potentials following Na+-induced depolarization is also crucial for salt stress tolerance. This stable membrane potential is sustained by the activity of Na+/H+ antiporters such as SOS1 at the PM. Moreover, novel regulators of Na+ and K+ transport pathways including the Nax1 and Nax2 loci regulation of SOS1

Calcium channel blockers ameliorate iron overload-associated hepatic fibrosis by altering iron transport and stellate cell apoptosis

Energy Technology Data Exchange (ETDEWEB)

Zhang, Ying [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Department of Pathology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang 050200, Hebei (China); Zhao, Xin [Department of Hepatobiliary Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei (China); Chang, Yanzhong [Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei (China); Zhang, Yuanyuan [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Chu, Xi [Department of Pharmacy, The Forth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei (China); Zhang, Xuan [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Liu, Zhenyi; Guo, Hui [Department of Medicinal Chemistry, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Wang, Na [Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Gao, Yonggang [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Zhang, Jianping, E-mail: zhangjianping14@126.com [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Chu, Li, E-mail: chuli0614@126.com [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei (China)

2016-06-15

Liver fibrosis is the principal cause of morbidity and mortality in patients with iron overload. Calcium channel blockers (CCBs) can antagonize divalent cation entry into renal and myocardial cells and inhibit fibrogenic gene expression. We investigated the potential of CCBs to resolve iron overload-associated hepatic fibrosis. Kunming mice were assigned to nine groups (n = 8 per group): control, iron overload, deferoxamine, high and low dose verapamil, high and low dose nimodipine, and high and low dose diltiazem. Iron deposition and hepatic fibrosis were measured in mouse livers. Expression levels of molecules associated with transmembrane iron transport were determined by molecular biology approaches. In vitro HSC-T6 cells were randomized into nine groups (the same groups as the mice). Changes in proliferation, apoptosis, and metalloproteinase expression in cells were detected to assess the anti-fibrotic effects of CCBs during iron overload conditions. We found that CCBs reduced hepatic iron content, intracellular iron deposition, the number of hepatic fibrotic areas, collagen expression levels, and hydroxyproline content. CCBs rescued abnormal expression of α1C protein in L-type voltage-dependent calcium channel (LVDCC) and down-regulated divalent metal transporter-1 (DMT-1) expression in mouse livers. In iron-overloaded HSC-T6 cells, CCBs reduced iron deposition, inhibited proliferation, induced apoptosis, and elevated expression of matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1). CCBs are potential therapeutic agents that can be used to address hepatic fibrosis during iron overload. They resolve hepatic fibrosis probably correlated with regulating transmembrane iron transport and inhibiting HSC growth. - Highlights: • Calcium channel blockers (CCBs) reduced hepatic iron content. • CCBs decreased hepatic fibrotic areas and collagen expression levels. • CCBs resolve fibrosis by regulating iron transport and

Active transport and heat.

Science.gov (United States)

Tait, Peter W

2011-07-01

Increasing heat may impede peoples' ability to be active outdoors thus limiting active transport options. Co-benefits from mitigation of and adaptation to global warming should not be assumed but need to be actively designed into strategies.

The Activation Effect of Hainantoxin-I, a Peptide Toxin from the Chinese Spider, Ornithoctonus hainana, on Intermediate-Conductance Ca2+-Activated K+ Channels

Directory of Open Access Journals (Sweden)

Pengfei Huang

2014-08-01

Full Text Available Intermediate-conductance Ca2+-activated K+ (IK channels are calcium/calmodulin-regulated voltage-independent K+ channels. Activation of IK currents is important in vessel and respiratory tissues, rendering the channels potential drug targets. A variety of small organic molecules have been synthesized and found to be potent activators of IK channels. However, the poor selectivity of these molecules limits their therapeutic value. Venom-derived peptides usually block their targets with high specificity. Therefore, we searched for novel peptide activators of IK channels by testing a series of toxins from spiders. Using electrophysiological experiments, we identified hainantoxin-I (HNTX-I as an IK-channel activator. HNTX-I has little effect on voltage-gated Na+ and Ca2+ channels from rat dorsal root ganglion neurons and on the heterologous expression of voltage-gated rapidly activating delayed rectifier K+ channels (human ether-à-go-go-related gene; human ERG in HEK293T cells. Only 35.2% ± 0.4% of the currents were activated in SK channels, and there was no effect on BK channels. We demonstrated that HNTX-I was not a phrenic nerve conduction blocker or acutely toxic. This is believed to be the first report of a peptide activator effect on IK channels. Our study suggests that the activity and selectivity of HNTX-I on IK channels make HNTX-I a promising template for designing new drugs for cardiovascular diseases.

The M2 Channel

DEFF Research Database (Denmark)

Santner, Paul

Drug resistance of Influenza A against antivirals is an increasing problem. No effective Influenza A drugs targeting the crucial viral protein, the proton transporter M2 are available anymore due to widespread resistance. Thanks to research efforts elucidating M2 protein structure, function and i...... resistance escape routes from drug inhibition. We thereby were hopefully able to provide a platform for the large-scale evaluation of M2 channel activity, inhibitors and resistance....

ATP-sensitive K(+-channels in muscle cells: features and physiological role

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O. B. Vadzyuk

2014-08-01

Full Text Available ATP-sensitive K+-channels of plasma membranes belong to the inward rectifier potassium channels type. They are involved in coupling of electrical activity of muscle cell with its metabolic­ state. These channels are heterooctameric and consist of two types of subunits: four poreforming (Kir 6.х and four regulatory (SUR, sulfonylurea receptor. The Kir subunits contain highly selective K+ filter and provide for high-velocity K+ currents. The SUR subunits contain binding sites for activators and blockers and have metabolic sensor, which enables channel activation under conditions of metabolic stress. ATP blocks K+ currents through the ATP-sensitive K+-channels in the most types of muscle cells. However, functional activity of these channels does not depend on absolute concentration of ATP but on the АТР/ADP ratio and presence of Mg2+. Physiologically active substances, such as phosphatidylinositol bisphosphate and fatty acid esters can regulate the activity of these structures in muscle cells. Activation of these channels under ischemic conditions underlies their cytoprotective action, which results in prevention of Ca2+ overload in cytosol. In contrast to ATP-sensitive K+-channels of plasma membranes, the data regarding the structure and function of ATP-sensitive K+-channels of mitochondrial membrane are contradictory. Pore-forming subunits of this channel have not been firmly identified yet. ATP-sensitive K+ transport through the mitochondrial­ membrane is easily tested by different methods, which are briefly reviewed in this paper. Interaction of mitoKATP with physiological and pharmacological ligands is discussed as well.

Orientation-Dependent Electronic Structures and Charge Transport Mechanisms in Ultrathin Polymeric n-Channel Field-Effect Transistors

NARCIS (Netherlands)

Fabiano, Simone; Yoshida, Hiroyuki; Chen, Zhihua; Facchetti, Antonio; Loi, Maria Antonietta

2013-01-01

We investigated the role of metal/organic semiconductor interface morphology on the charge transport mechanisms and energy level alignment of the n-channel semiconductor poly{[N,N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)} (P-(NDI2ODT2)).

Experimental investigations of plasma lens focusing and plasma channel transport of heavy ion beams

International Nuclear Information System (INIS)

Tauschwitz, T.; Yu, S.S.; Eylon, S.; Reginato, L.; Leemans, W.; Rasmussen, J.O.; Bangerter, R.O.

1995-04-01

Final focusing of ion beams and propagation in a reactor chamber are crucial questions for heavy ion beam driven Fusion. An alternative solution to ballistic quadrupole focusing, as it is proposed in most reactor studies today, is the utilization of the magnetic field produced by a high current plasma discharge. This plasma lens focusing concept relaxes the requirements for low emittance and energy spread of the driver beam significantly and allows to separate the issues of focusing, which can be accomplished outside the reactor chamber, and of beam transport inside the reactor. For focusing a tapered wall-stabilized discharge is proposed, a concept successfully demonstrated at GSI, Germany. For beam transport a laser pre-ionized channel can be used

Phosphorylation of rat brain purified mitochondrial Voltage-Dependent Anion Channel by c-Jun N-terminal kinase-3 modifies open-channel noise.

Science.gov (United States)

Gupta, Rajeev

2017-09-02

The drift kinetic energy of ionic flow through single ion channels cause vibrations of the pore walls which are observed as open-state current fluctuations (open-channel noise) during single-channel recordings. Vibration of the pore wall leads to transitions among different conformational sub-states of the channel protein in the open-state. Open-channel noise analysis can provide important information about the different conformational sub-state transitions and how biochemical modifications of ion channels would affect their transport properties. It has been shown that c-Jun N-terminal kinase-3 (JNK3) becomes activated by phosphorylation in various neurodegenerative diseases and phosphorylates outer mitochondrion associated proteins leading to neuronal apoptosis. In our earlier work, JNK3 has been reported to phosphorylate purified rat brain mitochondrial voltage-dependent anion channel (VDAC) in vitro and modify its conductance and opening probability. In this article we have compared the open-state noise profile of the native and the JNK3 phosphorylated VDAC using Power Spectral Density vs frequency plots. Power spectral density analysis of open-state noise indicated power law with average slope value α ≈1 for native VDAC at both positive and negative voltage whereas average α value open-state noise arises due to coupling of ionic transport and conformational sub-states transitions in open-state and this coupling is perturbed as a result of channel phosphorylation. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanisms of Rose Bengal inhibition on SecA ATPase and ion channel activities.

Science.gov (United States)

Hsieh, Ying-Hsin; Huang, Ying-Ju; Jin, Jin-Shan; Yu, Liyan; Yang, Hsiuchin; Jiang, Chun; Wang, Binghe; Tai, Phang C

2014-11-14

SecA is an essential protein possessing ATPase activity in bacterial protein translocation for which Rose Bengal (RB) is the first reported sub-micromolar inhibitor in ATPase activity and protein translocation. Here, we examined the mechanisms of inhibition on various forms of SecA ATPase by conventional enzymatic assays, and by monitoring the SecA-dependent channel activity in the semi-physiological system in cells. We build on the previous observation that SecA with liposomes form active protein-conducting channels in the oocytes. Such ion channel activity is enhanced by purified Escherichia coli SecYEG-SecDF·YajC liposome complexes. Inhibition by RB could be monitored, providing correlation of in vitro activity and intact cell functionality. In this work, we found the intrinsic SecA ATPase is inhibited by RB competitively at low ATP concentration, and non-competitively at high ATP concentrations while the translocation ATPase with precursors and SecYEG is inhibited non-competitively by RB. The Inhibition by RB on SecA channel activity in the oocytes with exogenous ATP-Mg(2+), mimicking translocation ATPase activity, is also non-competitive. The non-competitive inhibition on channel activity has also been observed with SecA from other bacteria which otherwise would be difficult to examine without the cognate precursors and membranes. Copyright © 2014 Elsevier Inc. All rights reserved.

Channel Power in Multi-Channel Environments

NARCIS (Netherlands)

M.G. Dekimpe (Marnik); B. Skiera (Bernd)

2004-01-01

textabstractIn the literature, little attention has been paid to instances where companies add an Internet channel to their direct channel portfolio. However, actively managing multiple sales channels requires knowing the customers’ channel preferences and the resulting channel power. Two key

International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels.

Science.gov (United States)

Kaczmarek, Leonard K; Aldrich, Richard W; Chandy, K George; Grissmer, Stephan; Wei, Aguan D; Wulff, Heike

2017-01-01

A subset of potassium channels is regulated primarily by changes in the cytoplasmic concentration of ions, including calcium, sodium, chloride, and protons. The eight members of this subfamily were originally all designated as calcium-activated channels. More recent studies have clarified the gating mechanisms for these channels and have documented that not all members are sensitive to calcium. This article describes the molecular relationships between these channels and provides an introduction to their functional properties. It also introduces a new nomenclature that differentiates between calcium- and sodium-activated potassium channels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity

Science.gov (United States)

Tien, Jason; Peters, Christian J; Wong, Xiu Ming; Cheng, Tong; Jan, Yuh Nung; Jan, Lily Yeh; Yang, Huanghe

2014-01-01

TMEM16A forms calcium-activated chloride channels (CaCCs) that regulate physiological processes such as the secretions of airway epithelia and exocrine glands, the contraction of smooth muscles, and the excitability of neurons. Notwithstanding intense interest in the mechanism behind TMEM16A-CaCC calcium-dependent gating, comprehensive surveys to identify and characterize potential calcium sensors of this channel are still lacking. By aligning distantly related calcium-activated ion channels in the TMEM16 family and conducting systematic mutagenesis of all conserved acidic residues thought to be exposed to the cytoplasm, we identify four acidic amino acids as putative calcium-binding residues. Alterations of the charge, polarity, and size of amino acid side chains at these sites alter the ability of different divalent cations to activate the channel. Furthermore, TMEM16A mutant channels containing double cysteine substitutions at these residues are sensitive to the redox potential of the internal solution, providing evidence for their physical proximity and solvent accessibility. DOI: http://dx.doi.org/10.7554/eLife.02772.001 PMID:24980701

Ca2+-dependent K+ Channels in Exocrine Salivary Glands

Science.gov (United States)

Catalán, Marcelo A.; Peña-Munzenmayer, Gaspar; Melvin, James E.

2014-01-01

In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function, including salivary glands. Among these proteins, Ca2+-dependent K+ channels take part in key functions including membrane potential regulation, fluid movement and K+ secretion in exocrine glands. Two K+ channels have been identified in exocrine salivary glands: 1) a Ca2+-activated K+ channel of intermediate single channel conductance encoded by the KCNN4 gene; and, 2) a voltage- and Ca2+-dependent K+ channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca2+-dependent K+ channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca2+-dependent K+ channels by protein-protein interactions that may significantly impact exocrine gland physiology. PMID:24559652

Pore size matters for potassium channel conductance

Science.gov (United States)

Moldenhauer, Hans; Pincuntureo, Matías

2016-01-01

Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K+ channels discriminate K+ over cations with similar radii with extraordinary selectivity and display a wide diversity of ion transport rates, covering differences of two orders of magnitude in unitary conductance. The pore domains of large- and small-conductance K+ channels share a general architectural design comprising a conserved narrow selectivity filter, which forms intimate interactions with permeant ions, flanked by two wider vestibules toward the internal and external openings. In large-conductance K+ channels, the inner vestibule is wide, whereas in small-conductance channels it is narrow. Here we raise the idea that the physical dimensions of the hydrophobic internal vestibule limit ion transport in K+ channels, accounting for their diversity in unitary conductance. PMID:27619418

Generalization of Spatial Channel Theory to Three-Dimensional x-y-z Transport Computations

International Nuclear Information System (INIS)

Abu-Shumays, I. K.; Hunter, M. A.; Martz, R. L.; Risner, J. M.

2002-01-01

Spatial channel theory, initially introduced in 1977 by M. L. Williams and colleagues at ORNL, is a powerful tool for shield design optimization. It focuses on so called ''contributon'' flux and current of particles (a fraction of the total of neutrons, photons, etc.) which contribute directly or through their progeny to a pre-specified response, such as a detector reading, dose rate, reaction rate, etc., at certain locations of interest. Particles that do not contribute directly or indirectly to the pre-specified response, such as particles that are absorbed or leak out, are ignored. Contributon fluxes and currents are computed based on combined forward and adjoint transport solutions. The initial concepts were considerably improved by Abu-Shumays, Selva, and Shure by introducing steam functions and response flow functions. Plots of such functions provide both qualitative and quantitative information on dominant particle flow paths and identify locations within a shield configuration that are important in contributing to the response of interest. Previous work was restricted to two dimensional (2-D) x-y rectangular and r-z cylindrical geometries. This paper generalizes previous work to three-dimensional x-y-z geometry, since it is now practical to solve realistic 3-D problems with multidimensional transport programs. As in previous work, new analytic expressions are provided for folding spherical harmonics representations of forward and adjoint transport flux solutions. As a result, the main integrals involve in spatial channel theory are computed exactly and more efficiently than by numerical quadrature. The analogy with incompressible fluid flow is also applied to obtain visual qualitative and quantitative measures of important streaming paths that could prove vital for shield design optimization. Illustrative examples are provided. The connection between the current paper and the excellent work completed by M. L. Williams in 1991 is also discussed

Two-group modeling of interfacial area transport in large diameter channels

Energy Technology Data Exchange (ETDEWEB)

Schlegel, J.P., E-mail: schlegelj@mst.edu [Department of Mining and Nuclear Engineering, Missouri University of Science and Technology, 301 W 14th St., Rolla, MO 65409 (United States); Hibiki, T.; Ishii, M. [School of Nuclear Engineering, Purdue University, 400 Central Dr., West Lafayette, IN 47907 (United States)

2015-11-15

Highlights: • Implemented updated constitutive models and benchmarking method for IATE in large pipes. • New model and method with new data improved the overall IATE prediction for large pipes. • Not all conditions well predicted shows that further development is still required. - Abstract: A comparison of the existing two-group interfacial area transport equation source and sink terms for large diameter channels with recently collected interfacial area concentration measurements (Schlegel et al., 2012, 2014. Int. J. Heat Fluid Flow 47, 42) has indicated that the model does not perform well in predicting interfacial area transport outside of the range of flow conditions used in the original benchmarking effort. In order to reduce the error in the prediction of interfacial area concentration by the interfacial area transport equation, several constitutive relations have been updated including the turbulence model and relative velocity correlation. The transport equation utilizing these updated models has been modified by updating the inter-group transfer and Group 2 coalescence and disintegration kernels using an expanded range of experimental conditions extending to pipe sizes of 0.304 m [12 in.], gas velocities of up to nearly 11 m/s [36.1 ft/s] and liquid velocities of up to 2 m/s [6.56 ft/s], as well as conditions with both bubbly flow and cap-bubbly flow injection (Schlegel et al., 2012, 2014). The modifications to the transport equation have resulted in a decrease in the RMS error for void fraction and interfacial area concentration from 17.32% to 12.3% and 21.26% to 19.6%. The combined RMS error, for both void fraction and interfacial area concentration, is below 15% for most of the experiments used in the comparison, a distinct improvement over the previous version of the model.

Soybean SAT1 (Symbiotic Ammonium Transporter 1) encodes a bHLH transcription factor involved in nodule growth and NH4+ transport.

Science.gov (United States)

Chiasson, David M; Loughlin, Patrick C; Mazurkiewicz, Danielle; Mohammadidehcheshmeh, Manijeh; Fedorova, Elena E; Okamoto, Mamoru; McLean, Elizabeth; Glass, Anthony D M; Smith, Sally E; Bisseling, Ton; Tyerman, Stephen D; Day, David A; Kaiser, Brent N

2014-04-01

Glycine max symbiotic ammonium transporter 1 was first documented as a putative ammonium (NH4(+)) channel localized to the symbiosome membrane of soybean root nodules. We show that Glycine max symbiotic ammonium transporter 1 is actually a membrane-localized basic helix-loop-helix (bHLH) DNA-binding transcription factor now renamed Glycine max bHLH membrane 1 (GmbHLHm1). In yeast, GmbHLHm1 enters the nucleus and transcriptionally activates a unique plasma membrane NH4(+) channel Saccharomyces cerevisiae ammonium facilitator 1. Ammonium facilitator 1 homologs are present in soybean and other plant species, where they often share chromosomal microsynteny with bHLHm1 loci. GmbHLHm1 is important to the soybean rhizobium symbiosis because loss of activity results in a reduction of nodule fitness and growth. Transcriptional changes in nodules highlight downstream signaling pathways involving circadian clock regulation, nutrient transport, hormone signaling, and cell wall modification. Collectively, these results show that GmbHLHm1 influences nodule development and activity and is linked to a novel mechanism for NH4(+) transport common to both yeast and plants.

Modulation of KCNQ4 channel activity by changes in cell volume

DEFF Research Database (Denmark)

Hougaard, Charlotte; Klaerke, Dan A; Hoffmann, Else K

2004-01-01

KCNQ4 channels expressed in HEK 293 cells are sensitive to cell volume changes, being activated by swelling and inhibited by shrinkage, respectively. The KCNQ4 channels contribute significantly to the regulatory volume decrease (RVD) process following cell swelling. Under isoosmotic conditions...

Chamber transport

International Nuclear Information System (INIS)

Olson, Craig L.

2001-01-01

Heavy ion beam transport through the containment chamber plays a crucial role in all heavy ion fusion (HIF) scenarios. Here, several parameters are used to characterize the operating space for HIF beams; transport modes are assessed in relation to evolving target/accelerator requirements; results of recent relevant experiments and simulations of HIF transport are summarized; and relevant instabilities are reviewed. All transport options still exist, including (1) vacuum ballistic transport, (2) neutralized ballistic transport, and (3) channel-like transport. Presently, the European HIF program favors vacuum ballistic transport, while the US HIF program favors neutralized ballistic transport with channel-like transport as an alternate approach. Further transport research is needed to clearly guide selection of the most attractive, integrated HIF system

Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels

Science.gov (United States)

Hei, Hongya; Li, Fangping; Wang, Yunman; Peng, Wen; Zhang, Xuemei

2015-01-01

Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α) and BK (α+β1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. PMID:26672753

Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels.

Directory of Open Access Journals (Sweden)

Qijing Chen

Full Text Available Large conductance Ca2+-activated potassium channels (BK are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α and BK (α+β1 currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1. Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms.

Cell swelling activates separate taurine and chloride channels in Ehrlich mouse ascites tumor cells

DEFF Research Database (Denmark)

Lambert, Ian Henry; Hoffmann, Else Kay

1994-01-01

The taurine efflux from Ehrlich ascites tumor cells is stimulated by hypotonic cell swelling. The swelling-activated taurine efflux is unaffected by substitution of gluconate for extracellular Cl– but inhibited by addition of MK196 (anion channel blocker) and 4,4 -diisothiocyanostilbene-2......,2 -disulfonic acid (DIDS; anion channel and anion exchange blocker) and by depolarization of the cell membrane. This is taken to indicate that taurine does not leave the osmotically swollen Ehrlich cells in exchange for extracellular Cl–, i.e., via the anion exchanger but via a MK196- and DIDS-sensitive channel...... that is potential dependent. An additional stimulation of the swelling-activated taurine efflux is seen after addition of arachidonic acid and oleic acid. Cell swelling also activates a Mini Cl– channel. The Cl– efflux via this Cl– channel, in contrast to the swelling-activated taurine efflux, is unaffected by DIDS...

Boosting the signal: Endothelial inward rectifier K+ channels.

Science.gov (United States)

Jackson, William F

2017-04-01

Endothelial cells express a diverse array of ion channels including members of the strong inward rectifier family composed of K IR 2 subunits. These two-membrane spanning domain channels are modulated by their lipid environment, and exist in macromolecular signaling complexes with receptors, protein kinases and other ion channels. Inward rectifier K + channel (K IR ) currents display a region of negative slope conductance at membrane potentials positive to the K + equilibrium potential that allows outward current through the channels to be activated by membrane hyperpolarization, permitting K IR to amplify hyperpolarization induced by other K + channels and ion transporters. Increases in extracellular K + concentration activate K IR allowing them to sense extracellular K + concentration and transduce this change into membrane hyperpolarization. These properties position K IR to participate in the mechanism of action of hyperpolarizing vasodilators and contribute to cell-cell conduction of hyperpolarization along the wall of microvessels. The expression of K IR in capillaries in electrically active tissues may allow K IR to sense extracellular K + , contributing to functional hyperemia. Understanding the regulation of expression and function of microvascular endothelial K IR will improve our understanding of the control of blood flow in the microcirculation in health and disease and may provide new targets for the development of therapeutics in the future. © 2016 John Wiley & Sons Ltd.

Activation of stretch-activated channels and maxi-K+ channels by membrane stress of human lamina cribrosa cells.

LENUS (Irish Health Repository)

Irnaten, Mustapha

2009-01-01

The lamina cribrosa (LC) region of the optic nerve head is considered the primary site of damage in glaucomatous optic neuropathy. Resident LC cells have a profibrotic potential when exposed to cyclical stretch. However, the mechanosensitive mechanisms of these cells remain unknown. Here the authors investigated the effects of membrane stretch on cell volume change and ion channel activity and examined the associated changes in intracellular calcium ([Ca(2+)](i)).

Calcium-Activated Cl- Channel: Insights on the Molecular Identity in Epithelial Tissues.

Science.gov (United States)

Rottgen, Trey S; Nickerson, Andrew J; Rajendran, Vazhaikkurichi M

2018-05-10

Calcium-activated chloride secretion in epithelial tissues has been described for many years. However, the molecular identity of the channel responsible for the Ca 2+ -activated Cl − secretion in epithelial tissues has remained a mystery. More recently, TMEM16A has been identified as a new putative Ca 2+ -activated Cl − channel (CaCC). The primary goal of this article will be to review the characterization of TMEM16A, as it relates to the physical structure of the channel, as well as important residues that confer voltage and Ca 2+ -sensitivity of the channel. This review will also discuss the role of TMEM16A in epithelial physiology and potential associated-pathophysiology. This will include discussion of developed knockout models that have provided much needed insight on the functional localization of TMEM16A in several epithelial tissues. Finally, this review will examine the implications of the identification of TMEM16A as it pertains to potential novel therapies in several pathologies.

Phosphatidylinositol 4,5-bisphosphate, cholesterol, and fatty acids modulate the calcium-activated chloride channel TMEM16A (ANO1).

Science.gov (United States)

De Jesús-Pérez, José J; Cruz-Rangel, Silvia; Espino-Saldaña, Ángeles E; Martínez-Torres, Ataúlfo; Qu, Zhiqiang; Hartzell, H Criss; Corral-Fernandez, Nancy E; Pérez-Cornejo, Patricia; Arreola, Jorge

2018-03-01

The TMEM16A-mediated Ca 2+ -activated Cl - current drives several important physiological functions. Membrane lipids regulate ion channels and transporters but their influence on members of the TMEM16 family is poorly understood. Here we have studied the regulation of TMEM16A by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), cholesterol, and fatty acids using patch clamp, biochemistry and fluorescence microscopy. We found that depletion of membrane PI(4,5)P2 causes a decline in TMEM16A current that is independent of cytoskeleton, but is partially prevented by removing intracellular Ca 2+ . On the other hand, supplying PI(4,5)P2 to inside-out patches attenuated channel rundown and/or partially rescued activity after channel rundown. Also, depletion (with methyl-β-cyclodextrin M-βCD) or restoration (with M-βCD+cholesterol) of membrane cholesterol slows down the current decay observed after reduction of PI(4,5)P2. Neither depletion nor restoration of cholesterol change PI(4,5)P2 content. However, M-βCD alone transiently increases TMEM16A activity and dampens rundown whereas M-βCD+cholesterol increases channel rundown. Thus, PI(4,5)P2 is required for TMEM16A function while cholesterol directly and indirectly via a PI(4,5)P2-independent mechanism regulate channel function. Stearic, arachidonic, oleic, docosahexaenoic, and eicosapentaenoic fatty acids as well as methyl stearate inhibit TMEM16A in a dose- and voltage-dependent manner. Phosphatidylserine, a phospholipid whose hydrocarbon tails contain stearic and oleic acids also inhibits TMEM16A. Finally, we show that TMEM16A remains in the plasma membrane after treatment with M-βCD, M-βCD+cholesterol, oleic, or docosahexaenoic acids. Thus, we propose that lipids and fatty acids regulate TMEM16A channels through a membrane-delimited protein-lipid interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidics and microscale transport processes

CERN Document Server

Chakraborty, Suman

2012-01-01

With an intense focus on micro- and nanotechnology from a fluidic perspective, this book details the research activities in key directions on both the theoretical and experimental fronts. As part of the IIT Kharagpur Research Monograph series, the text discusses topics such as capillary transport in microchannels, fluid friction and heat transfer in microchannels, electrokinetics, and interfacial transport in nanochannels. It also covers nanoparticle transport in colloidal suspensions, bubble generation in microfluidic channels, micro-heat pipe, the lattice Boltzmann method for phase changing

Upgrade of optical WDM transport systems introducing linerates at 40 Gbit/s per channel

Science.gov (United States)

Schneiders, Malte; Vorbeck, Sascha; Aust, Nora

2006-10-01

Driven by high growth rates of internet traffic the question of upgrading existing optical metro-, regio- and long haul transport networks introducing 40 Gbit/s/λ is one of the most important questions today and in the near future. Current WDM Systems in photonic networks are commonly operated at linerates of 2.5 and 10 Gbit/s/λ. Induced by market analyses and the historical development of transport systems some work has already been carried out to evaluate update scenarios from 10 to 40 Gbit/s channel data rates. Due to the inherent quadruplication of the bandwidth per channel, limitations due to linear and non-linear transmission impairments become stronger resulting in a highly increased complexity of link engineering, potentially increasing the capital and operational expenditures. A lot of work is therefore in progress, which targets at the relaxation of constraints for 40 Gbit/s transmission to find the most efficient upgrade strategies. One approach towards an increased robustness against signal distortions is the introduction of more advanced modulation formats. Different modulation schemes show strongly different optical WDM transmission characteristics. The choice of the appropriate format does not only depend on the technical requirements, but also on economical considerations as an increased transmitter- and receiver-complexity will drive the transponder price. This article presents investigations on different modulation formats for the upgrade of existing metro-/ regio and long haul transport networks. Tolerances and robustness against the main degrading effects dispersion, noise and nonlinearities are considered together with mitigation strategies like the adaptation of dispersion maps. Results from numerical simulations are provided for some of the most promising modulation formats like NRZ, RZ, CS-RZ, Optical Duobinary and DPSK.

5-HT1A receptors modulate small-conductance Ca2+-activated K+ channels

DEFF Research Database (Denmark)

Grunnet, Morten; Jespersen, Thomas; Perrier, Jean-François

2004-01-01

Small-conductance calcium-activated potassium channels (SK) are responsible for the medium afterhyperpolarisation (mAHP) following action potentials in neurons. Here we tested the ability of serotonin (5-HT) to modulate the activity of SK channels by coexpressing 5-HT1A receptors with different...

An approach to implement virtual channels for flowing magnetic beads

International Nuclear Information System (INIS)

Tang, Shih-Hao; Chiang, Hung-Wei; Hsieh, Min-Chien; Chang, Yen-Di; Yeh, Po-Fan; Tsai, Jui-che; Shieh, Wung-Yang

2014-01-01

This work demonstrates the feasibility of a novel microfluidic system with virtual channels formed by ‘walls’ of magnetic fields, including collecting channels, transporting channels and function channels. The channels are defined by the nickel patterns. With its own ferromagnetism, nickel can be magnetized using an external magnetic field; the nickel structures then generate magnetic fields that can either guide or trap magnetic beads. A glass substrate is sandwiched between the liquid containing magnetic beads and the chip with nickel structures, preventing the liquid from directly contacting the nickel. In this work, collecting channels, transporting channels and function channels are displayed sequentially. In the collecting channel portion, channels with different shapes are compared. Next, in the transporting channel portion we demonstrate I-, S- and Y-shaped channels can steer magnetic beads smoothly. Finally, in the function channel portion, a switchable trapping channel implemented with a bistable mechanism performs the passing and blocking of a magnetic bead. (paper)

Measurements of stability limits for a space-charge-dominated ion beam in a long A.G. transport channel

International Nuclear Information System (INIS)

Tiefenback, M.G.; Keefe, D.

1985-05-01

The Single Beam Transport Experiment at LBL consists of 82 electrostatic quadrupole lenses arranged in a FODO lattice. Five further lenses provide a matched beam from a high-current high-brightness cesium source for injection into the FODO channel. We call the transport conditions stable if both the emittance and current remain unchanged between the beginning and end of the channel, and unstable if either the emittance grows or the current decreases because of collective effects. We have explored the range of single-particle betatron phase advance per period from sigma 0 = 45 0 to 150 0 to determine the stability limits for the space-charge depressed phase advance, sigma. No lower limit for sigma (down to 7 0 ) has been found at sigma 0 = 60 0 , whereas limits have clearly been identified and mapped in the region of sigma 0 above 90 0

Ginseng gintonin activates the human cardiac delayed rectifier K+ channel: involvement of Ca2+/calmodulin binding sites.

Science.gov (United States)

Choi, Sun-Hye; Lee, Byung-Hwan; Kim, Hyeon-Joong; Jung, Seok-Won; Kim, Hyun-Sook; Shin, Ho-Chul; Lee, Jun-Hee; Kim, Hyoung-Chun; Rhim, Hyewhon; Hwang, Sung-Hee; Ha, Tal Soo; Kim, Hyun-Ji; Cho, Hana; Nah, Seung-Yeol

2014-09-01

Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca(2+)]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K(+) (I(Ks)) channel is a cardiac K(+) channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating I(Ks) channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human I(Ks) channel activity by expressing human I(Ks) channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the I(Ks) channel was 0.05 ± 0.01 μg/ml. Gintonin-mediated activation of the I(Ks) channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the I(Ks) channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca(2+)]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on I(Ks) channel. However, gintonin had no effect on hERG K(+) channel activity. These results show that gintonin-mediated enhancement of I(Ks) channel currents is achieved through binding of the [Ca(2+)]i/CaM complex to the C terminus of KCNQ1 subunit.

Downregulation of Kv7.4 channel activity in primary and secondary hypertension

DEFF Research Database (Denmark)

Jepps, Thomas Andrew; Chadha, Preet S; Davis, Alison J

2011-01-01

Voltage-gated potassium (K(+)) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of...... structurally different activators of Kv7.2 through Kv7.5 channels (BMS-204352, S-1, and retigabine) on blood vessels from normotensive and hypertensive animals.......Voltage-gated potassium (K(+)) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of 3...

Biochemical and structural analysis of the hyperpolarization-activated K(+) channel MVP.

Science.gov (United States)

Randich, Amelia M; Cuello, Luis G; Wanderling, Sherry S; Perozo, Eduardo

2014-03-18

In contrast to the majority of voltage-gated ion channels, hyperpolarization-activated channels remain closed at depolarizing potentials and are activated at hyperpolarizing potentials. The basis for this reverse polarity is thought to be a result of differences in the way the voltage-sensing domain (VSD) couples to the pore domain. In the absence of structural data, the molecular mechanism of this reverse polarity coupling remains poorly characterized. Here we report the characterization of the structure and local dynamics of the closed activation gate (lower S6 region) of MVP, a hyperpolarization-activated potassium channel from Methanococcus jannaschii, by electron paramagnetic resonance (EPR) spectroscopy. We show that a codon-optimized version of MVP has high expression levels in Escherichia coli, is purified as a stable tetramer, and exhibits expected voltage-dependent activity when reconstituted in liposomes. EPR analysis of the mid to lower S6 region revealed positions exhibiting strong spin-spin coupling, indicating that the activation gate of MVP is closed at 0 mV. A comparison of local environmental parameters along the activation gate for MVP and KcsA indicates that MVP adopts a different closed conformation. These structural details set the stage for future evaluations of reverse electromechanical coupling in MVP.

Biochemical and Structural Analysis of the Hyperpolarization-Activated K+ Channel MVP

Science.gov (United States)

2015-01-01

In contrast to the majority of voltage-gated ion channels, hyperpolarization-activated channels remain closed at depolarizing potentials and are activated at hyperpolarizing potentials. The basis for this reverse polarity is thought to be a result of differences in the way the voltage-sensing domain (VSD) couples to the pore domain. In the absence of structural data, the molecular mechanism of this reverse polarity coupling remains poorly characterized. Here we report the characterization of the structure and local dynamics of the closed activation gate (lower S6 region) of MVP, a hyperpolarization-activated potassium channel from Methanococcus jannaschii, by electron paramagnetic resonance (EPR) spectroscopy. We show that a codon-optimized version of MVP has high expression levels in Escherichia coli, is purified as a stable tetramer, and exhibits expected voltage-dependent activity when reconstituted in liposomes. EPR analysis of the mid to lower S6 region revealed positions exhibiting strong spin–spin coupling, indicating that the activation gate of MVP is closed at 0 mV. A comparison of local environmental parameters along the activation gate for MVP and KcsA indicates that MVP adopts a different closed conformation. These structural details set the stage for future evaluations of reverse electromechanical coupling in MVP. PMID:24490868

Radon transport processes below the earth's surface

International Nuclear Information System (INIS)

Wilkening, M.

1980-01-01

Processes by which 222 Rn is transported from the soil to the earth's surface are reviewed. The mechanisms effective in transporting 222 Rn to the surface are related to the size and configuration of the spaces occupied by the soil gas which may vary from molecular interstices to large underground caverns. The near-surface transport processes are divided into two categories: (1) a microscopic process that includes molecular diffusion and viscous flow in fine capillaries and (2) macroscopic flow in fissures and channels. Underground air rich in 222 Rn can also reach the surface through cracks, fissures, and underground channels. This type of transport is shown for (1) a horizontal tunnel penetrating a fractured hillside, (2) a large underground cave, and (3) volcanic activity. Pressure differentials having various natural origins and thermal gradients are responsible for the transport in these examples. 222 Rn transport by ordinary molecular diffusion appears to be the dominant process

Interplay between spatially explicit sediment sourcing, hierarchical river-network structure, and in-channel bed material sediment transport and storage dynamics

Science.gov (United States)

Czuba, Jonathan A.; Foufoula-Georgiou, Efi; Gran, Karen B.; Belmont, Patrick; Wilcock, Peter R.

2017-05-01

Understanding how sediment moves along source to sink pathways through watersheds—from hillslopes to channels and in and out of floodplains—is a fundamental problem in geomorphology. We contribute to advancing this understanding by modeling the transport and in-channel storage dynamics of bed material sediment on a river network over a 600 year time period. Specifically, we present spatiotemporal changes in bed sediment thickness along an entire river network to elucidate how river networks organize and process sediment supply. We apply our model to sand transport in the agricultural Greater Blue Earth River Basin in Minnesota. By casting the arrival of sediment to links of the network as a Poisson process, we derive analytically (under supply-limited conditions) the time-averaged probability distribution function of bed sediment thickness for each link of the river network for any spatial distribution of inputs. Under transport-limited conditions, the analytical assumptions of the Poisson arrival process are violated (due to in-channel storage dynamics) where we find large fluctuations and periodicity in the time series of bed sediment thickness. The time series of bed sediment thickness is the result of dynamics on a network in propagating, altering, and amalgamating sediment inputs in sometimes unexpected ways. One key insight gleaned from the model is that there can be a small fraction of reaches with relatively low-transport capacity within a nonequilibrium river network acting as "bottlenecks" that control sediment to downstream reaches, whereby fluctuations in bed elevation can dissociate from signals in sediment supply.

Channel Morphology and Bed Sediment Characteristics Before and After Habitat Enhancement Activities in the Uridil Property, Platte River, Nebraska, Water Years 2005-2008

Science.gov (United States)

Kinzel, Paul J.

2009-01-01

Fluvial geomorphic data were collected by the United States Geological Survey from July 2005 to June 2008 (a time period within water years 2005 to 2008) to monitor the effects of habitat enhancement activities conducted in the Platte River Whooping Crane Maintenance Trust's Uridil Property, located along the Platte River, Nebraska. The activities involved the removal of vegetation and sand from the tops of high permanent islands and the placement of the sand into the active river channel. This strategy was intended to enhance habitat for migratory water birds by lowering the elevations of the high islands, thereby eliminating a visual obstruction for roosting birds. It was also thought that the bare sand on the lowered island surfaces could serve as potential habitat for nesting water birds. Lastly, the project supplied a local source of sediment to the river to test the hypothesis that this material could contribute to the formation of lower sandbars and potential nesting sites downstream. Topographic surveys on the islands and along river transects were used to quantify the volume of removed sand and track the storage and movement of the introduced sand downstream. Sediment samples were also collected to map the spatial distribution of river bed sediment sizes before and after the management activities. While the project lowered the elevation of high islands, observations of the sand addition indicated the relatively fine-grained sand that was placed in the active river channel was rapidly transported by the flowing water. Topographic measurements made 3 months after the sand addition along transects in the area of sediment addition showed net aggradation over measurements made in 2005. In the year following the sand addition, 2007, elevated river flows from local rain events generally were accompanied by net degradation along transects within the area of sediment addition. In the spring of 2008, a large magnitude flow event of approximately 360 cubic meters per

Control of the Water Transport Activity of Barley HvTIP3;1 Specifically Expressed in Seeds.

Science.gov (United States)

Utsugi, Shigeko; Shibasaka, Mineo; Maekawa, Masahiko; Katsuhara, Maki

2015-09-01

Tonoplast intrinsic proteins (TIPs) are involved in the transport and storage of water, and control intracellular osmotic pressure by transporting material related to the water potential of cells. In the present study, we focused on HvTIP3;1 during the periods of seed development and desiccation in barley. HvTIP3;1 was specifically expressed in seeds. An immunochemical analysis showed that HvTIP3;1 strongly accumulated in the aleurone layers and outer layers of barley seeds. The water transport activities of HvTIP3;1 and HvTIP1;2, which also accumulated in seeds, were measured in the heterologous expression system of Xenopus oocytes. When they were expressed individually, HvTIP1;2 transported water, whereas HvTIP3;1 did not. However, HvTIP3;1 exhibited water transport activity when co-expressed with HvTIP1;2 in oocytes, and this activity was higher than when HvTIP1;2 was expressed alone. This is the first report to demonstrate that the water permeability of a TIP aquaporin was activated when co-expressed with another TIP. The split-yellow fluorescent protein (YFP) system in onion cells revealed that HvTIP3;1 interacted with HvTIP1;2 to form a heterotetramer in plants. These results suggest that HvTIP3;1 functions as an active water channel to regulate water movement through tissues during the periods of seed development and desiccation. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Activation of protein kinase C alters the intracellular distribution and mobility of cardiac Na+ channels.

Science.gov (United States)

Hallaq, Haifa; Wang, Dao W; Kunic, Jennifer D; George, Alfred L; Wells, K Sam; Murray, Katherine T

2012-02-01

Na(+) current derived from expression of the cardiac isoform SCN5A is reduced by receptor-mediated or direct activation of protein kinase C (PKC). Previous work has suggested a possible role for loss of Na(+) channels at the plasma membrane in this effect, but the results are controversial. In this study, we tested the hypothesis that PKC activation acutely modulates the intracellular distribution of SCN5A channels and that this effect can be visualized in living cells. In human embryonic kidney cells that stably expressed SCN5A with green fluorescent protein (GFP) fused to the channel COOH-terminus (SCN5A-GFP), Na(+) currents were suppressed by an exposure to PKC activation. Using confocal microscopy, colocalization of SCN5A-GFP channels with the plasma membrane under control and stimulated conditions was quantified. A separate population of SCN5A channels containing an extracellular epitope was immunolabeled to permit temporally stable labeling of the plasma membrane. Our results demonstrated that Na(+) channels were preferentially trafficked away from the plasma membrane by PKC activation, with a major contribution by Ca(2+)-sensitive or conventional PKC isoforms, whereas stimulation of protein kinase A (PKA) had the opposite effect. Removal of the conserved PKC site Ser(1503) or exposure to the NADPH oxidase inhibitor apocynin eliminated the PKC-mediated effect to alter channel trafficking, indicating that both channel phosphorylation and ROS were required. Experiments using fluorescence recovery after photobleaching demonstrated that both PKC and PKA also modified channel mobility in a manner consistent with the dynamics of channel distribution. These results demonstrate that the activation of protein kinases can acutely regulate the intracellular distribution and molecular mobility of cardiac Na(+) channels in living cells.

A family of fluoride-specific ion channels with dual-topology architecture.

Science.gov (United States)

Stockbridge, Randy B; Robertson, Janice L; Kolmakova-Partensky, Ludmila; Miller, Christopher

2013-08-27

Fluoride ion, ubiquitous in soil, water, and marine environments, is a chronic threat to microorganisms. Many prokaryotes, archea, unicellular eukaryotes, and plants use a recently discovered family of F(-) exporter proteins to lower cytoplasmic F(-) levels to counteract the anion's toxicity. We show here that these 'Fluc' proteins, purified and reconstituted in liposomes and planar phospholipid bilayers, form constitutively open anion channels with extreme selectivity for F(-) over Cl(-). The active channel is a dimer of identical or homologous subunits arranged in antiparallel transmembrane orientation. This dual-topology assembly has not previously been seen in ion channels but is known in multidrug transporters of the SMR family, and is suggestive of an evolutionary antecedent of the inverted repeats found within the subunits of many membrane transport proteins. DOI:http://dx.doi.org/10.7554/eLife.01084.001.

A lattice Boltzmann model for solute transport in open channel flow

Science.gov (United States)

Wang, Hongda; Cater, John; Liu, Haifei; Ding, Xiangyi; Huang, Wei

2018-01-01

A lattice Boltzmann model of advection-dispersion problems in one-dimensional (1D) open channel flows is developed for simulation of solute transport and pollutant concentration. The hydrodynamics are calculated based on a previous lattice Boltzmann approach to solving the 1D Saint-Venant equations (LABSVE). The advection-dispersion model is coupled with the LABSVE using the lattice Boltzmann method. Our research recovers the advection-dispersion equations through the Chapman-Enskog expansion of the lattice Boltzmann equation. The model differs from the existing schemes in two points: (1) the lattice Boltzmann numerical method is adopted to solve the advection-dispersion problem by meso-scopic particle distribution; (2) and the model describes the relation between discharge, cross section area and solute concentration, which increases the applicability of the water quality model in practical engineering. The model is verified using three benchmark tests: (1) instantaneous solute transport within a short distance; (2) 1D point source pollution with constant velocity; (3) 1D point source pollution in a dam break flow. The model is then applied to a 50-year flood point source pollution accident on the Yongding River, which showed good agreement with a MIKE 11 solution and gauging data.

Controllable transport of a skyrmion in a ferromagnetic narrow channel with voltage-controlled magnetic anisotropy

Science.gov (United States)

Wang, Junlin; Xia, Jing; Zhang, Xichao; Zhao, G. P.; Ye, Lei; Wu, Jing; Xu, Yongbing; Zhao, Weisheng; Zou, Zhigang; Zhou, Yan

2018-05-01

Magnetic skyrmions have potential applications in next-generation spintronic devices with ultralow energy consumption. In this work, the current-driven skyrmion motion in a narrow ferromagnetic nanotrack with voltage-controlled magnetic anisotropy (VCMA) is studied numerically. By utilizing the VCMA effect, the transport of skyrmion can be unidirectional in the nanotrack, leading to a one-way information channel. The trajectory of the skyrmion can also be modulated by periodically located VCMA gates, which protects the skyrmion from destruction by touching the track edge. In addition, the location of the skyrmion can be controlled by adjusting the driving pulse length in the presence of the VCMA effect. Our results provide guidelines for practical realization of the skyrmion-based information channel, diode, and skyrmion-based electronic devices such as racetrack memory.

Cloning, functional expression, and characterization of a PKA-activated gastric Cl- channel.

Science.gov (United States)

Malinowska, D H; Kupert, E Y; Bahinski, A; Sherry, A M; Cuppoletti, J

1995-01-01

cDNA encoding a Cl- channel was isolated from a rabbit gastric library, sequenced, and expressed in Xenopus oocytes. The predicted protein (898 amino acids, relative molecular mass 98,433 Da) was overall 93% similar to the rat brain ClC-2 Cl- channel. However, a 151-amino acid stretch toward the COOH-terminus was 74% similar to ClC-2 with six amino acids deleted. Two new potential protein kinase A (PKA) phosphorylation sites (also protein kinase C phosphorylation sites) were introduced. cRNA-injected Xenopus oocytes expressed a Cl- channel that was active at pHtrans 3 and had a linear current-voltage (I-V) curve and a slope conductance of 29 +/- 1 pS at 800 mM CsCl. A fivefold Cl- gradient caused a rightward shift in the I-V curve with a reversal potential of +30 +/- 3 mV, indicating anion selectivity. The selectivity was I- > Cl- > NO3-. The native and recombinant Cl- channel were both activated in vitro by PKA catalytic subunit and ATP. The electrophysiological and regulatory properties of the cloned and the native channel were similar. The cloned protein may be the Cl- channel involved in gastric HCl secretion.

Activation of lysosomal P2X4 by ATP transported into lysosomes via VNUT/SLC17A9 using V‐ATPase generated voltage gradient as the driving force

Science.gov (United States)

Zhong, Xi Zoë; Cao, Qi; Sun, Xue

2016-01-01

Key points SLC17A9 proteins function as a lysosomal ATP transporter responsible for lysosomal ATP accumulation.P2X4 receptors act as lysosomal ion channels activated by luminal ATP.SLC17A9‐mediated ATP transport across the lysosomal membrane is suppressed by Bafilomycin A1, the V‐ATPase inhibitor.SLC17A9 mainly uses voltage gradient but not pH gradient generated by the V‐ATPase as the driving force to transport ATP into the lysosome to activate P2X4. Abstract The lysosome contains abundant ATP which plays important roles in lysosome functions and in cell signalling. Recently, solute carrier family 17 member 9 (SLC17A9, also known as VNUT for vesicular nucleotide transporter) proteins were suggested to function as a lysosomal ATP transporter responsible for lysosomal ATP accumulation, and P2X4 receptors were suggested to be lysosomal ion channels that are activated by luminal ATP. However, the molecular mechanism of SLC17A9 transporting ATP and the regulatory mechanism of lysosomal P2X4 are largely unknown. In this study, we report that SLC17A9‐mediated ATP transport across lysosomal membranes is suppressed by Bafilomycin A1, the V‐ATPase inhibitor. By measuring P2X4 activity, which is indicative of ATP transport across lysosomal membranes, we further demonstrated that SLC17A9 mainly uses voltage gradient but not pH gradient as the driving force to transport ATP into lysosomes. This study provides a molecular mechanism for lysosomal ATP transport mediated by SLC17A9. It also suggests a regulatory mechanism of lysosomal P2X4 by SLC17A9. PMID:27477609

A chimeric prokaryotic pentameric ligand–gated channel reveals distinct pathways of activation

Science.gov (United States)

Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.; Stein, Richard A.; Bonner, Ross; Talley, Lauren; Parker, Mark D.; Mchaourab, Hassane S.; Yee, Vivien C.; Lodowski, David T.

2015-01-01

Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators. PMID:26415570

Cholesterol regulates HERG K+ channel activation by increasing phospholipase C β1 expression.

Science.gov (United States)

Chun, Yoon Sun; Oh, Hyun Geun; Park, Myoung Kyu; Cho, Hana; Chung, Sungkwon

2013-01-01

Human ether-a-go-go-related gene (HERG) K(+) channel underlies the rapidly activating delayed rectifier K(+) conductance (IKr) during normal cardiac repolarization. Also, it may regulate excitability in many neuronal cells. Recently, we showed that enrichment of cell membrane with cholesterol inhibits HERG channels by reducing the levels of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] due to the activation of phospholipase C (PLC). In this study, we further explored the effect of cholesterol enrichment on HERG channel kinetics. When membrane cholesterol level was mildly increased in human embryonic kidney (HEK) 293 cells expressing HERG channel, the inactivation and deactivation kinetics of HERG current were not affected, but the activation rate was significantly decelerated at all voltages tested. The application of PtdIns(4,5)P2 or inhibitor for PLC prevented the effect of cholesterol enrichment, while the presence of antibody against PtdIns(4,5)P2 in pipette solution mimicked the effect of cholesterol enrichment. These results indicate that the effect of cholesterol enrichment on HERG channel is due to the depletion of PtdIns(4,5)P2. We also found that cholesterol enrichment significantly increases the expression of β1 and β3 isoforms of PLC (PLCβ1, PLCβ3) in the membrane. Since the effects of cholesterol enrichment on HERG channel were prevented by inhibiting transcription or by inhibiting PLCβ1 expression, we conclude that increased PLCβ1 expression leads to the deceleration of HERG channel activation rate via downregulation of PtdIns(4,5)P2. These results confirm a crosstalk between two plasma membrane-enriched lipids, cholesterol and PtdIns(4,5)P2, in the regulation of HERG channels.

Polystyrene nanoparticles activate ion transport in human airway epithelial cells

Directory of Open Access Journals (Sweden)

McCarthy J

2011-06-01

Full Text Available J McCarthy1, X Gong2, D Nahirney2, M Duszyk2, MW Radomski11School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Physiology, University of Alberta, Edmonton, Alberta, CanadaBackground: Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have the potential to provide new therapies for many lung diseases. In this study, we investigated the acute effects of polystyrene nanoparticles on epithelial ion channel function.Methods: Human submucosal Calu-3 cells that express cystic fibrosis transmembrane conductance regulator (CFTR and baby hamster kidney cells engineered to express the wild-type CFTR gene were used to investigate the actions of negatively charged 20 nm polystyrene nanoparticles on short-circuit current in Calu-3 cells by Ussing chamber and single CFTR Cl- channels alone and in the presence of known CFTR channel activators by using baby hamster kidney cell patches.Results: Polystyrene nanoparticles caused sustained, repeatable, and concentration-dependent increases in short-circuit current. In turn, these short-circuit current responses were found to be biphasic in nature, ie, an initial peak followed by a plateau. EC50 values for peak and plateau short-circuit current responses were 1457 and 315.5 ng/mL, respectively. Short-circuit current was inhibited by diphenylamine-2-carboxylate, a CFTR Cl- channel blocker. Polystyrene nanoparticles activated basolateral K+ channels and affected Cl- and HCO3- secretion. The mechanism of short-circuit current activation by polystyrene nanoparticles was found to be largely dependent on calcium-dependent and cyclic nucleotide-dependent phosphorylation of CFTR Cl- channels. Recordings from isolated inside-out patches using baby hamster kidney cells confirmed the direct activation of CFTR Cl- channels by the nanoparticles.Conclusion: This is the first study to identify

Ion Transport in Confined Geometries below the Nanoscale: Access Resistance Dominates Protein Channel Conductance in Diluted Solutions.

Science.gov (United States)

Alcaraz, Antonio; López, M Lidón; Queralt-Martín, María; Aguilella, Vicente M

2017-10-24

Synthetic nanopores and mesoscopic protein channels have common traits like the importance of electrostatic interactions between the permeating ions and the nanochannel. Ion transport at the nanoscale occurs under confinement conditions so that the usual assumptions made in microfluidics are challenged, among others, by interfacial effects such as access resistance (AR). Here, we show that a sound interpretation of electrophysiological measurements in terms of channel ion selective properties requires the consideration of interfacial effects, up to the point that they dominate protein channel conductance in diluted solutions. We measure AR in a large ion channel, the bacterial porin OmpF, by means of single-channel conductance measurements in electrolyte solutions containing varying concentrations of high molecular weight PEG, sterically excluded from the pore. Comparison of experiments performed in charged and neutral planar membranes shows that lipid surface charges modify the ion distribution and determine the value of AR, indicating that lipid molecules are more than passive scaffolds even in the case of large transmembrane proteins. We also found that AR may reach up to 80% of the total channel conductance in diluted solutions, where electrophysiological recordings register essentially the AR of the system and depend marginally on the pore characteristics. These findings may have implications for several low aspect ratio biological channels that perform their physiological function in a low ionic strength and macromolecule crowded environment, just the two conditions enhancing the AR contribution.

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

Science.gov (United States)

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Dynamic behavior of liquid water transport in a tapered channel of a proton exchange membrane fuel cell cathode

NARCIS (Netherlands)

Akhtar, N.; Kerkhof, P.J.A.M.

2011-01-01

A numerical model of a proton exchange membrane fuel cell (PEMFC) cathode with a tapered channel design has been developed in order to examine the dynamic behavior of liquid water transport. Three-dimensional, transient simulations employing the level-set method (available in COMSOL 3.5a, a

Temperature dependence of the transport properties of spin field-effect transistors built with InAs and Si channels

Science.gov (United States)

Osintsev, D.; Sverdlov, V.; Stanojević, Z.; Makarov, A.; Selberherr, S.

2012-05-01

We study the transport properties of the Datta-Das spin field-effect transistor built on InAs and Si. First, we demonstrate that the amplitude of the magnetoresistance oscillations as a function of the band mismatch between the ferromagnetic contacts and the semiconductor channel made of InAs decreases dramatically with increasing temperature. A shorter InAs channel is needed to create an InAs-based SpinFET which will operate at higher temperatures. Second, we show that the [1 0 0] orientation of the fin is preferable for silicon SpinFETs due to stronger modulation of the conductance as a function of spin-orbit interaction and magnetic field. Short silicon fins can be used for current modulation as a function of the conduction band mismatch between the channel and the ferromagnetic contacts only at relatively low temperatures. In contrast, longer silicon channels allow a TMR modulation at room temperature by changing the strength of the spin-orbit interaction through the gate bias.

Transport and storage of bed material in a gravel-bed channel during episodes of aggradation and degradation: a field and flume study

Science.gov (United States)

Bonnie Smith Pryor; Thomas Lisle; Diane Sutherland Montoya; Sue Hilton

2011-01-01

The dynamics of sediment transport capacity in gravel-bed rivers is critical to understanding the formation and preservation of fluvial landforms and formulating sediment-routing models in drainage systems. We examine transport-storage relations during cycles of aggradation and degradation by augmenting observations of three events of channel aggradation and...

P2Y2 and P2Y4 receptors regulate pancreatic Ca²+-activated K+ channels differently

DEFF Research Database (Denmark)

Klærke, Susanne Edeling Hede; Amstrup, Jan; Klærke, Dan Arne

2005-01-01

Extracellular ATP is an important regulator of transepithelial transport in a number of tissues. In pancreatic ducts, we have shown that ATP modulates epithelial K+ channels via purinergic receptors, most likely the P2Y2 and P2Y4 receptors, but the identity of the involved K+ channels was not cle...

Activation gating kinetics of GIRK channels are mediated by cytoplasmic residues adjacent to transmembrane domains.

Science.gov (United States)

Sadja, Rona; Reuveny, Eitan

2009-01-01

G-protein-coupled inwardly rectifying potassium channels (GIRK/Kir3.x) are involved in neurotransmission-mediated reduction of excitability. The gating mechanism following G protein activation of these channels likely proceeds from movement of inner transmembrane helices to allow K(+) ions movement through the pore of the channel. There is limited understanding of how the binding of G-protein betagamma subunits to cytoplasmic regions of the channel transduces the signal to the transmembrane regions. In this study, we examined the molecular basis that governs the activation kinetics of these channels, using a chimeric approach. We identified two regions as being important in determining the kinetics of activation. One region is the bottom of the outer transmembrane helix (TM1) and the cytoplasmic domain immediately adjacent (the slide helix); and the second region is the bottom of the inner transmembrane helix (TM2) and the cytoplasmic domain immediately adjacent. Interestingly, both of these regions are sufficient in mediating the kinetics of fast activation gating. This result suggests that there is a cooperative movement of either one of these domains to allow fast and efficient activation gating of GIRK channels.

Immunolocalization and expression of small-conductance calcium-activated potassium channels in human myometrium

DEFF Research Database (Denmark)

Rosenbaum, Sofia T; Svalø, Julie; Nielsen, Karsten

2012-01-01

Small-conductance calcium-activated potassium (SK3) channels have been detected in human myometrium and we have previously shown a functional role of SK channels in human myometrium in vitro. The aims of this study were to identify the precise localization of SK3 channels and to quantify SK3 m....... This is the first report to provide evidence for a possible role of SK3 channels in human uterine telocytes....

High porosity harzburgite and dunite channels for the transport of compositionally heterogeneous melts in the mantle: II. Geochemical consequences

Science.gov (United States)

Liang, Y.; Schiemenz, A.; Xia, Y.; Parmentier, E.

2009-12-01

In a companion numerical study [1], we explored the spatial distribution of high porosity harzburgite and dunite channels produced by reactive dissolution of orthopyroxene (opx) in an upwelling mantle column and identified a number of new features. In this study, we examine the geochemical consequences of channelized melt flow under the settings outlined in [1] with special attention to the transport of compositionally heterogeneous melts and their interactions with the surrounding peridotite matrix during melt migration in the mantle. Time-dependent transport equations for a trace element in the interstitial melt and solids that include advection, dispersion, and melt-rock reaction were solved in a 2-D upwelling column using the high-order numerical methods outlined in [1]. The melt and solid velocities were taken from the steady state or quasi-steady state solutions of [1]. In terms of trace element fractionation, the simulation domain can be divided into 4 distinct regions: (a) high porosity harzburgite channel, overlain by; (b) high porosity dunite channel; (c) low porosity compacting boundary layer surrounding the melt channels; and (d) inter-channel regions outside (c). In the limit of local chemical equilibrium, melting in region (d) is equivalent to batch melting, whereas melting and melt extraction in (c) is more close to fractional melting with the melt suction rate first increase from the bottom of the melting column to a maximum near the bottom of the dunite channel and then decrease upward in the compacting boundary layer. The melt composition in the high porosity harzburgite channel is similar to that produced by high-degree batch melting (up to opx exhaustion), whereas the melt composition in the dunite is a weighted average of the ultra-depleted melt from the harzburgite channel below, the expelled melt from the compacting boundary layer, and melt produced by opx dissolution along the sidewalls of the dunite channel. Compaction within the dunite

Evidence that Na+-pumping occurs through the D-channel in Vitreoscilla cytochrome bo

International Nuclear Information System (INIS)

Kim, Seong K.; Stark, Benjamin C.; Webster, Dale A.

2005-01-01

The operon (cyo) encoding the Na + -pumping respiratory terminal oxidase (cytochrome bo) of the bacterium Vitreoscilla was transformed into Escherichia coli GV100, a deletion mutant of cytochrome bo. This was done for the wild type operon and five mutants in three conserved Cyo subunit I amino acids known to be crucial for H + transport in the E. coli enzyme, one near the nuclear center, one in the K-channel, and one in the D-channel. CO-binding, NADH and ubiquinol oxidase, and Na + -pumping activities were all substantially inhibited by each mutation. The wild type Vitreoscilla cytochrome bo can pump Na + against a concentration gradient, resulting in a transmembrane concentration differential of 2-3 orders of magnitude. It is proposed that Vitreoscilla cytochrome bo pumps four Na + through the D-channel to the exterior and transports four H + through the K-channel for the reduction of each O 2

ALTERNATIVE EQUATIONS FOR DYNAMIC BEHAVIOR OF IONIC CHANNEL ACTIVATION AND INACTIVATION GATES

Directory of Open Access Journals (Sweden)

Mahmut ÖZER

2003-03-01

Full Text Available In this paper, alternative equations for dynamics of ionic channel activation and inactivation gates are proposed based on the path probability method. Dynamic behavior of a voltage-gated ionic channel is modeled by the conventional Hodgkin-Huxley (H-H mathematical formalism. In that model, conductance of the channel is defined in terms of activation and inactivation gates. Dynamics of the activation and inactivation gates is modeled by first-order differential equations dependent on the gate variable and the membrane potential. In the new approach proposed in this study, dynamic behavior of activation and inactivation gates is modeled by a firstorder differential equation dependent on internal energy and membrane potential by using the path probability method which is widely used in statistical physics. The new model doesn't require the time constant and steadystate values which are used explicitly in the H-H model. The numerical results show validity of the proposed method.

Osteopontin activates the diabetes-associated potassium channel TALK-1 in pancreatic β-cells.

Directory of Open Access Journals (Sweden)

Matthew T Dickerson

Full Text Available Glucose-stimulated insulin secretion (GSIS relies on β-cell Ca2+ influx, which is modulated by the two-pore-domain K+ (K2P channel, TALK-1. A gain-of-function polymorphism in KCNK16, the gene encoding TALK-1, increases risk for developing type-2 diabetes. While TALK-1 serves an important role in modulating GSIS, the regulatory mechanism(s that control β-cell TALK-1 channels are unknown. Therefore, we employed a membrane-specific yeast two-hybrid (MYTH assay to identify TALK-1-interacting proteins in human islets, which will assist in determining signaling modalities that modulate TALK-1 function. Twenty-one proteins from a human islet cDNA library interacted with TALK-1. Some of these interactions increased TALK-1 activity, including intracellular osteopontin (iOPN. Intracellular OPN is highly expressed in β-cells and is upregulated under pre-diabetic conditions to help maintain normal β-cell function; however, the functional role of iOPN in β-cells is poorly understood. We found that iOPN colocalized with TALK-1 in pancreatic sections and coimmunoprecipitated with human islet TALK-1 channels. As human β-cells express two K+ channel-forming variants of TALK-1, regulation of these TALK-1 variants by iOPN was assessed. At physiological voltages iOPN activated TALK-1 transcript variant 3 channels but not TALK-1 transcript variant 2 channels. Activation of TALK-1 channels by iOPN also hyperpolarized resting membrane potential (Vm in HEK293 cells and in primary mouse β-cells. Intracellular OPN was also knocked down in β-cells to test its effect on β-cell TALK-1 channel activity. Reducing β-cell iOPN significantly decreased TALK-1 K+ currents and increased glucose-stimulated Ca2+ influx. Importantly, iOPN did not affect the function of other K2P channels or alter Ca2+ influx into TALK-1 deficient β-cells. These results reveal the first protein interactions with the TALK-1 channel and found that an interaction with iOPN increased �

Structural mechanism underlying capsaicin binding and activation of TRPV1 ion channel

OpenAIRE

Yang, Fan; Xiao, Xian; Cheng, Wei; Yang, Wei; Yu, Peilin; Song, Zhenzhen; Yarov-Yarovoy, Vladimir; Zheng, Jie

2015-01-01

Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2-to-4.5 ? resolution, however important details required for mechanistic understandings are unavailable: capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions. We obtained the missing atomic-level details by iterative computation, which were c...

Conductance of Ion Channels - Theory vs. Experiment

Science.gov (United States)

Pohorille, Andrew; Wilson, Michael; Mijajlovic, Milan

2013-01-01

Transmembrane ion channels mediate a number of essential physiological processes in a cell ranging from regulating osmotic pressure to transmission of neural signals. Kinetics and selectivity of ion transport is of critical importance to a cell and, not surprisingly, it is a subject of numerous experimental and theoretical studies. In this presentation we will analyze in detail computer simulations of two simple channels from fungi - antiamoebin and trichotoxin. Each of these channels is made of an alpha-helical bundle of small, nongenomically synthesized peptides containing a number of rare amino acids and exhibits strong antimicrobial activity. We will focus on calculating ionic conductance defined as the ratio of ionic current through the channel to applied voltage. From molecular dynamics simulations, conductance can be calculated in at least two ways, each involving different approximations. Specifically, the current, given as the number of charges transferred through the channel per unit of time, can be obtained from the number of events in which ions cross the channel during the simulation. This method works well for large currents (high conductance values and/or applied voltages). If the number of crossing events is small, reliable estimates of current are difficult to achieve. Alternatively, conductance can be estimated assuming that ion transport can be well approximated as diffusion in the external potential given by the free energy profile. Then, the current can be calculated by solving the one-dimensional diffusion equation in this external potential and applied voltage (the generalized Nernst-Planck equation). To do so three ingredients are needed: the free energy profile, the position-dependent diffusion coefficient and the diffusive flux of ions into the channel. All these quantities can be obtained from molecular dynamics simulations. An important advantage of this method is that it can be used equally well to estimating large and small currents

Melatonin mediates vasodilation through both direct and indirect activation of BKCa channels.

Science.gov (United States)

Zhao, T; Zhang, H; Jin, C; Qiu, F; Wu, Y; Shi, L

2017-10-01

Melatonin, synthesized primarily by the pineal gland, is a neuroendocrine hormone with high membrane permeability. The vascular effects of melatonin, including vasoconstriction and vasodilation, have been demonstrated in numerous studies. However, the mechanisms underlying these effects are not fully understood. Large-conductance Ca 2+ -activated K + (BK Ca ) channels are expressed broadly on smooth muscle cells and play an important role in vascular tone regulation. This study explored the mechanisms of myocyte BK Ca channels and endothelial factors underlying the action of melatonin on the mesenteric arteries (MAs). Vascular contractility and patch-clamp studies were performed on myocytes of MAs from Wistar rats. Melatonin induced significant vasodilation on MAs. In the presence of N ω -nitro-l-arginine methyl ester (l-NAME), a potent endothelial oxide synthase (eNOS) inhibitor, melatonin elicited concentration-dependent relaxation, with lowered pIC 50 The effect of melatonin was significantly attenuated in the presence of BK Ca channel blocker iberiotoxin or MT1/MT2 receptor antagonist luzindole in both (+) l-NAME and (-) l-NAME groups. In the (+) l-NAME group, iberiotoxin caused a parallel rightward shift of the melatonin concentration-relaxation curve, with pIC 50 lower than that of luzindole. Both inside-out and cell-attached patch-clamp recordings showed that melatonin significantly increased the open probability, mean open time and voltage sensitivity of BK Ca channels. In a cell-attached patch-clamp configuration, the melatonin-induced enhancement of BK Ca channel activity was significantly suppressed by luzindole. These findings indicate that in addition to the activation of eNOS, melatonin-induced vasorelaxation of MAs is partially attributable to its direct (passing through the cell membrane) and indirect (via MT1/MT2 receptors) activation of the BK Ca channels on mesenteric arterial myocytes. © 2017 Society for Endocrinology.

Transport of biologically active material in laser cutting.

Science.gov (United States)

Frenz, M; Mathezloic, F; Stoffel, M H; Zweig, A D; Romano, V; Weber, H P

1988-01-01

The transport of biologically active material during laser cutting with CO2 and Er lasers is demonstrated. This transport mechanism removes particles from the surface of gelatin, agar, and liver samples into the depth of the laser-formed craters. The transport phenomenon is explained by a contraction and condensation of enclosed hot water vapor. We show by cultivating transported bacteria in agar that biological particles can survive the shock of the transport. Determination of the numbers of active cells evidences a more pronounced activity of the cultivated bacteria after impact with an Er laser than with a CO2 laser.

Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.

Directory of Open Access Journals (Sweden)

Arne Bilet

Full Text Available NS1643 is one of the small molecule HERG (Kv11.1 channel activators and has also been found to increase erg2 (Kv11.2 currents. We now investigated whether NS1643 is also able to act as an activator of Kv11.3 (erg3 channels expressed in CHO cells. Activation of rat Kv11.3 current occurred in a dose-dependent manner and maximal current increasing effects were obtained with 10 µM NS1643. At this concentration, steady-state outward current increased by about 80% and the current increase was associated with a significant shift in the voltage dependence of activation to more negative potentials by about 15 mV. In addition, activation kinetics were accelerated, whereas deactivation was slowed. There was no significant effect on the kinetics of inactivation and recovery from inactivation. The strong current-activating agonistic effect of NS1643 did not result from a shift in the voltage dependence of Kv11.3 channel inactivation and was independent from external Na(+ or Ca(2+. At the higher concentration of 20 µM, NS1643 induced clearly less current increase. The left shift in the voltage dependence of activation reversed and the voltage sensitivity of activation dramatically decreased along with a slowing of Kv11.3 channel activation. These data show that, in comparison to other Kv11 family members, NS1643 exerts distinct effects on Kv11.3 channels with especially pronounced partial antagonistic effects at higher concentration.

Slack sodium-activated potassium channel membrane expression requires p38 mitogen-activated protein kinase phosphorylation.

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Gururaj, Sushmitha; Fleites, John; Bhattacharjee, Arin

2016-04-01

p38 MAPK has long been understood as an inducible kinase under conditions of cellular stress, but there is now increasing evidence to support its role in the regulation of neuronal function. Several phosphorylation targets have been identified, an appreciable number of which are ion channels, implicating the possible involvement of p38 MAPK in neuronal excitability. The KNa channel Slack is an important protein to be studied as it is highly and ubiquitously expressed in DRG neurons and is important in the maintenance of their firing accommodation. We sought to examine if the Slack channel could be a substrate of p38 MAPK activity. First, we found that the Slack C-terminus contains two putative p38 MAPK phosphorylation sites that are highly conserved across species. Second, we show via electrophysiology experiments that KNa currents and further, Slack currents, are subject to tonic modulation by p38 MAPK. Third, biochemical approaches revealed that Slack channel regulation by p38 MAPK occurs through direct phosphorylation at the two putative sites of interaction, and mutating both sites prevented surface expression of Slack channels. Based on these results, we conclude that p38 MAPK is an obligate regulator of Slack channel function via the trafficking of channels into the membrane. The present study identifies Slack KNa channels as p38 MAPK substrates. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ion Transport in Organic Electrolyte Solution through the Pore Channels of Anodic Nanoporous Alumina Membranes

International Nuclear Information System (INIS)

Fukutsuka, Tomokazu; Koyamada, Kohei; Maruyama, Shohei; Miyazaki, Kohei; Abe, Takeshi

2016-01-01

Highlights: • Ion transport in organic electrolyte solution in macro- and meso-pores was focused. • Anodic nanoporous alumina membrane was used as a porous material. • The specific ion conductivities drastically decreased in macro- and meso-pores. - Abstract: For the development of high energy density lithium-ion batteries with the high rate performance, the enhancement of the ion transport in the electrolyte solutions impregnated in the porous electrodes is a key. To study the ion transport in porous electrodes, anodic nanoporous alumina (APA) self-standing membranes with macro- or meso-pores were used as model porous materials. These membranes had nearly spherical pore channels of discrete 20–68 nm in diameters. By using the geometric shape of the pores, we attempted to evaluate the specific ion conductivities of the organic electrolyte solution dissolving lithium salt simply. AC impedance spectroscopy measurement of a four-electrode cell with membranes showed one depressed semi-circle in the Nyquist plots and this semi-circle can be assigned as the ion transport resistance in the pores. The specific ion conductivities evaluated from the ion transport resistances and the geometric parameters showed very small values, even in the macro-pores, as compared with that of the bulk electrolyte solution.

Molecular analysis of a thylakoid K+channel

International Nuclear Information System (INIS)

1999-01-01

The work undertaken sought to use a novel probe to identify and clone plant ion (K) channels. It was also proposed that in vitro biochemical studies of cation transport across purified preparations of thylakoid membrane be employed to characterize a putative K channel in this membrane system. Over the last several years, an enormous data base of partially-sequenced mRNAs and numerous genomes (including those of plants) has evolved and provides a powerful alternative to this brute-force approach to identify and clone cDNAs encoding physiologically important membrane proteins such as channels. The utility of searching genetic databases for relevant sequences, in addition to the difficulty of working with membrane proteins, led to changes in research focus during the granting period. During the course of the funding period, work was finished up which documented the presence of a K channel in the thylakoid membrane and demonstrated that K fluxes through this channel were required for optimal photosynthetic activity, likely due to the requirement for charge balancing of proton flux

Molecular analysis of a thylakoid K+channel

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-09-10

The work undertaken sought to use a novel probe to identify and clone plant ion (K) channels. It was also proposed that in vitro biochemical studies of cation transport across purified preparations of thylakoid membrane be employed to characterize a putative K channel in this membrane system. Over the last several years, an enormous data base of partially-sequenced mRNAs and numerous genomes (including those of plants) has evolved and provides a powerful alternative to this brute-force approach to identify and clone cDNAs encoding physiologically important membrane proteins such as channels. The utility of searching genetic databases for relevant sequences, in addition to the difficulty of working with membrane proteins, led to changes in research focus during the granting period. During the course of the funding period, work was finished up which documented the presence of a K channel in the thylakoid membrane and demonstrated that K fluxes through this channel were required for optimal photosynthetic activity, likely due to the requirement for charge balancing of proton flux.

Dendritic calcium channels and their activation by synaptic signals in auditory coincidence detector neurons.

Science.gov (United States)

Blackmer, Trillium; Kuo, Sidney P; Bender, Kevin J; Apostolides, Pierre F; Trussell, Laurence O

2009-08-01

The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting the coincidence of binaural signals. Accurate coincidence detection requires precise developmental regulation of the lengths of the fine, bitufted dendrites that characterize neurons in NL. Such regulation has been suggested to be driven by local, synaptically mediated, dendritic signals such as Ca(2+). We examined Ca(2+) signaling through patch clamp and ion imaging experiments in slices containing nucleus laminaris from embryonic chicks. Voltage-clamp recordings of neurons located in the NL showed the presence of large Ca(2+) currents of two types, a low voltage-activated, fast inactivating Ni(2+) sensitive channel resembling mammalian T-type channels, and a high voltage-activated, slowly inactivating Cd(2+) sensitive channel. Two-photon Ca(2+) imaging showed that both channel types were concentrated on dendrites, even at their distal tips. Single action potentials triggered synaptically or by somatic current injection immediately elevated Ca(2+) throughout the entire cell. Ca(2+) signals triggered by subthreshold synaptic activity were highly localized. Thus when electrical activity is suprathreshold, Ca(2+) channels ensure that Ca(2+) rises in all dendrites, even those that are synaptically inactive.

Hydrodynamics and sediment transport in a meandering channel with a model axial-flow hydrokinetic turbine

Science.gov (United States)

Hill, Craig; Kozarek, Jessica; Sotiropoulos, Fotis; Guala, Michele

2016-02-01

An investigation into the interactions between a model axial-flow hydrokinetic turbine (rotor diameter, dT = 0.15 m) and the complex hydrodynamics and sediment transport processes within a meandering channel was carried out in the Outdoor StreamLab research facility at the University of Minnesota St. Anthony Falls Laboratory. This field-scale meandering stream with bulk flow and sediment discharge control provided a location for high spatiotemporally resolved measurements of bed and water surface elevations around the model turbine. The device was installed within an asymmetric, erodible channel cross section under migrating bed form and fixed outer bank conditions. A comparative analysis between velocity and topographic measurements, with and without the turbine installed, highlights the local and nonlocal features of the turbine-induced scour and deposition patterns. In particular, it shows how the cross-section geometry changes, how the bed form characteristics are altered, and how the mean flow field is distorted both upstream and downstream of the turbine. We further compare and discuss how current energy conversion deployments in meander regions would result in different interactions between the turbine operation and the local and nonlocal bathymetry compared to straight channels.

Cell Membrane Transport Mechanisms: Ion Channels and Electrical Properties of Cell Membranes.

Science.gov (United States)

Kulbacka, Julita; Choromańska, Anna; Rossowska, Joanna; Weżgowiec, Joanna; Saczko, Jolanta; Rols, Marie-Pierre

2017-01-01

Cellular life strongly depends on the membrane ability to precisely control exchange of solutes between the internal and external (environmental) compartments. This barrier regulates which types of solutes can enter and leave the cell. Transmembrane transport involves complex mechanisms responsible for passive and active carriage of ions and small- and medium-size molecules. Transport mechanisms existing in the biological membranes highly determine proper cellular functions and contribute to drug transport. The present chapter deals with features and electrical properties of the cell membrane and addresses the questions how the cell membrane accomplishes transport functions and how transmembrane transport can be affected. Since dysfunctions of plasma membrane transporters very often are the cause of human diseases, we also report how specific transport mechanisms can be modulated or inhibited in order to enhance the therapeutic effect.

Update on vascular endothelial Ca(2+) signalling: A tale of ion channels, pumps and transporters.

Science.gov (United States)

Moccia, Francesco; Berra-Romani, Roberto; Tanzi, Franco

2012-07-26

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca(2+) signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca(2+) levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca(2+) signals, ranging from brief, localized Ca(2+) pulses to prolonged Ca(2+) oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca(2+) signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca(2+) releasing channels, which are located both on the plasma membrane and in a number of intracellular organelles, and Ca(2+) removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca(2+) machinery in vascular ECs under both physiological and pathological conditions.

Update on vascular endothelial Ca2+ signalling: A tale of ion channels, pumps and transporters

Science.gov (United States)

Moccia, Francesco; Berra-Romani, Roberto; Tanzi, Franco

2012-01-01

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca2+ signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca2+ levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca2+ signals, ranging from brief, localized Ca2+ pulses to prolonged Ca2+ oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca2+ signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca2+ releasing channels, which are located both on the plasma membrane and in a number of intracellular organelles, and Ca2+ removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca2+ machinery in vascular ECs under both physiological and pathological conditions. PMID:22905291

Analytical solution of electrohydrodynamic flow and transport in rectangular channels: inclusion of double layer effects

KAUST Repository

Joekar-Niasar, V.

2013-01-25

Upscaling electroosmosis in porous media is a challenge due to the complexity and scale-dependent nonlinearities of this coupled phenomenon. "Pore-network modeling" for upscaling electroosmosis from pore scale to Darcy scale can be considered as a promising approach. However, this method requires analytical solutions for flow and transport at pore scale. This study concentrates on the development of analytical solutions of flow and transport in a single rectangular channel under combined effects of electrohydrodynamic forces. These relations will be used in future works for pore-network modeling. The analytical solutions are valid for all regimes of overlapping electrical double layers and have the potential to be extended to nonlinear Boltzmann distribution. The innovative aspects of this study are (a) contribution of overlapping of electrical double layers to the Stokes flow as well as Nernst-Planck transport has been carefully included in the analytical solutions. (b) All important transport mechanisms including advection, diffusion, and electromigration have been included in the analytical solutions. (c) Fully algebraic relations developed in this study can be easily employed to upscale electroosmosis to Darcy scale using pore-network modeling. © 2013 Springer Science+Business Media Dordrecht.

Analytical solution of electrohydrodynamic flow and transport in rectangular channels: inclusion of double layer effects

KAUST Repository

Joekar-Niasar, V.; Schotting, R.; Leijnse, A.

2013-01-01

Upscaling electroosmosis in porous media is a challenge due to the complexity and scale-dependent nonlinearities of this coupled phenomenon. "Pore-network modeling" for upscaling electroosmosis from pore scale to Darcy scale can be considered as a promising approach. However, this method requires analytical solutions for flow and transport at pore scale. This study concentrates on the development of analytical solutions of flow and transport in a single rectangular channel under combined effects of electrohydrodynamic forces. These relations will be used in future works for pore-network modeling. The analytical solutions are valid for all regimes of overlapping electrical double layers and have the potential to be extended to nonlinear Boltzmann distribution. The innovative aspects of this study are (a) contribution of overlapping of electrical double layers to the Stokes flow as well as Nernst-Planck transport has been carefully included in the analytical solutions. (b) All important transport mechanisms including advection, diffusion, and electromigration have been included in the analytical solutions. (c) Fully algebraic relations developed in this study can be easily employed to upscale electroosmosis to Darcy scale using pore-network modeling. © 2013 Springer Science+Business Media Dordrecht.

Trap density of states in n-channel organic transistors: variable temperature characteristics and band transport

International Nuclear Information System (INIS)

Cho, Joung-min; Akiyama, Yuto; Kakinuma, Tomoyuki; Mori, Takehiko

2013-01-01

We have investigated trap density of states (trap DOS) in n-channel organic field-effect transistors based on N,N ’-bis(cyclohexyl)naphthalene diimide (Cy-NDI) and dimethyldicyanoquinonediimine (DMDCNQI). A new method is proposed to extract trap DOS from the Arrhenius plot of the temperature-dependent transconductance. Double exponential trap DOS are observed, in which Cy-NDI has considerable deep states, by contrast, DMDCNQI has substantial tail states. In addition, numerical simulation of the transistor characteristics has been conducted by assuming an exponential trap distribution and the interface approximation. Temperature dependence of transfer characteristics are well reproduced only using several parameters, and the trap DOS obtained from the simulated characteristics are in good agreement with the assumed trap DOS, indicating that our analysis is self-consistent. Although the experimentally obtained Meyer-Neldel temperature is related to the trap distribution width, the simulation satisfies the Meyer-Neldel rule only very phenomenologically. The simulation also reveals that the subthreshold swing is not always a good indicator of the total trap amount, because it also largely depends on the trap distribution width. Finally, band transport is explored from the simulation having a small number of traps. A crossing point of the transfer curves and negative activation energy above a certain gate voltage are observed in the simulated characteristics, where the critical V G above which band transport is realized is determined by the sum of the trapped and free charge states below the conduction band edge

Reconfigurable virtual electrowetting channels.

Science.gov (United States)

Banerjee, Ananda; Kreit, Eric; Liu, Yuguang; Heikenfeld, Jason; Papautsky, Ian

2012-02-21

Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are almost always application specific and far from a true "laboratory." The second involves electrowetting droplet movement (digital microfluidics), and allows two-dimensional computer control of fluidic transport and mixing. The merging of the two paradigms in the form of programmable electrowetting channels takes advantage of both the "continuous" functionality of rigid channels based on which a large number of applications have been developed to date and the "programmable" functionality of digital microfluidics that permits electrical control of on-chip functions. In this work, we demonstrate for the first time programmable formation of virtual microfluidic channels and their continuous operation with pressure driven flows using an electrowetting platform. Experimental, theoretical, and numerical analyses of virtual channel formation with biologically relevant electrolyte solutions and electrically-programmable reconfiguration are presented. We demonstrate that the "wall-less" virtual channels can be formed reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven transport in these virtual channels at flow rates up to 100 μL min(-1) is achievable without distortion of the channel shape. We further demonstrate that these virtual channels can be switched on-demand between multiple inputs and outputs. Ultimately, we envision a platform that would provide rapid prototyping of microfluidic concepts and would be capable of a vast library of functions and benefitting applications from clinical diagnostics in resource-limited environments to rapid system prototyping to high throughput pharmaceutical applications.

Detection of TRPV4 channel current-like activity in Fawn Hooded hypertensive (FHH rat cerebral arterial muscle cells.

Directory of Open Access Journals (Sweden)

Debebe Gebremedhin

Full Text Available The transient receptor potential vallinoid type 4 (TRPV4 is a calcium entry channel known to modulate vascular function by mediating endothelium-dependent vasodilation. The present study investigated if isolated cerebral arterial myocytes of the Fawn Hooded hypertensive (FHH rat, known to display exaggerated KCa channel current activity and impaired myogenic tone, express TRPV4 channels at the transcript and protein level and exhibit TRPV4-like single-channel cationic current activity. Reverse transcription polymerase chain reaction (RT-PCR, Western blot, and immunostaining analysis detected the expression of mRNA transcript and translated protein of TRPV4 channel in FHH rat cerebral arterial myocytes. Patch clamp recording of single-channel current activity identified the presence of a single-channel cationic current with unitary conductance of ~85 pS and ~96 pS at hyperpolarizing and depolarizing potentials, respectively, that was inhibited by the TRPV4 channel antagonist RN 1734 or HC 067074 and activated by the potent TRPV4 channel agonist GSK1016790A. Application of negative pressure via the interior of the patch pipette increased the NPo of the TRPV4-like single-channel cationic current recorded in cell-attached patches at a patch potential of 60 mV that was inhibited by prior application of the TRPV4 channel antagonist RN 1734 or HC 067047. Treatment with the TRPV4 channel agonist GSK1016790A caused concentration-dependent increase in the NPo of KCa single-channel current recorded in cell-attached patches of cerebral arterial myocytes at a patch potential of 40 mV, which was not influenced by pretreatment with the voltage-gated L-type Ca2+ channel blocker nifedipine or the T-type Ca2+ channel blocker Ni2+. These findings demonstrate that FHH rat cerebral arterial myocytes express mRNA transcript and translated protein for TRPV4 channel and display TRPV4-like single-channel cationic current activity that was stretch-sensitive and

Effect of surface bilayer charges on the magnetic field around ionic channels

Energy Technology Data Exchange (ETDEWEB)

Gomes Soares, Marília Amável [Post-graduation in Computational Sciences, Rio de Janeiro State University (Brazil); Cortez, Celia Martins, E-mail: ccortezs@ime.uerj.br [Post-graduation in Computational Sciences, Rio de Janeiro State University (Brazil); Department of Applied Mathematics, Rio de Janeiro State University (Brazil); Oliveira Cruz, Frederico Alan de [Post-graduation in Computational Sciences, Rio de Janeiro State University (Brazil); Department of Physics, Rural Federal University of Rio de Janeiro (Brazil); Silva, Dilson [Post-graduation in Computational Sciences, Rio de Janeiro State University (Brazil); Department of Applied Mathematics, Rio de Janeiro State University (Brazil)

2017-01-01

In this work, we present a physic-mathematical model for representing the ion transport through membrane channels, in special Na{sup +} and K{sup +}-channels, and discuss the influence of surface bilayer charges on the magnetic field behavior around the ionic current. The model was composed of a set of equations, including: a nonlinear differential Poisson-Boltzmann equation which usually allows to estimate the surface potentials and electric potential profile across membrane; equations for the ionic flux through channel and the ionic current density based on Armstrong's model for Na{sup +} and K{sup +} permeability and other Physics concepts; and a magnetic field expression derived from the classical Ampère equation. Results from computational simulations using the finite element method suggest that the ionic permeability is strongly dependent of surface bilayer charges, the current density through a K{sup +}-channel is very less sensible to temperature changes than the current density through a Na{sup +}- channel, active Na{sup +}-channels do not directly interfere with the K{sup +}-channels around, and vice-versa, since the magnetic perturbation generated by an active channel is of short-range.

cAMP-dependent kinase does not modulate the Slack sodium-activated potassium channel.

Science.gov (United States)

Nuwer, Megan O; Picchione, Kelly E; Bhattacharjee, Arin

2009-09-01

The Slack gene encodes a Na(+)-activated K(+) channel and is expressed in many different types of neurons. Like the prokaryotic Ca(2+)-gated K(+) channel MthK, Slack contains two 'regulator of K(+) conductance' (RCK) domains within its carboxy terminal, domains likely involved in Na(+) binding and channel gating. It also contains multiple consensus protein kinase C (PKC) and protein kinase A (PKA) phosphorylation sites and although regulated by protein kinase C (PKC) phosphorylation, modulation by PKA has not been determined. To test if PKA directly regulates Slack, nystatin-perforated patch whole-cell currents were recorded from a human embryonic kidney (HEK-293) cell line stably expressing Slack. Bath application of forskolin, an adenylate cyclase activator, caused a rapid and complete inhibition of Slack currents however, the inactive homolog of forskolin, 1,9-dideoxyforskolin caused a similar effect. In contrast, bath application of 8-bromo-cAMP did not affect the amplitude nor the activation kinetics of Slack currents. In excised inside-out patch recordings, direct application of the PKA catalytic subunit to patches did not affect the open probability of Slack channels nor was open probability affected by direct application of protein phosphatase 2B. Preincubation of cells with the protein kinase A inhibitor KT5720 also did not change current density. Finally, mutating the consensus phosphorylation site located between RCK domain 1 and domain 2 from serine to glutamate did not affect current activation kinetics. We conclude that unlike PKC, phosphorylation by PKA does not acutely modulate the function and gating activation kinetics of Slack channels.

Burst activity and ultrafast activation kinetics of CaV1.3 Ca²⁺ channels support presynaptic activity in adult gerbil hair cell ribbon synapses.

Science.gov (United States)

Zampini, Valeria; Johnson, Stuart L; Franz, Christoph; Knipper, Marlies; Holley, Matthew C; Magistretti, Jacopo; Masetto, Sergio; Marcotti, Walter

2013-08-15

Auditory information transfer to afferent neurons relies on precise triggering of neurotransmitter release at the inner hair cell (IHC) ribbon synapses by Ca²⁺ entry through CaV1.3 Ca²⁺ channels. Despite the crucial role of CaV1.3 Ca²⁺ channels in governing synaptic vesicle fusion, their elementary properties in adult mammals remain unknown. Using near-physiological recording conditions we investigated Ca²⁺ channel activity in adult gerbil IHCs. We found that Ca²⁺ channels are partially active at the IHC resting membrane potential (-60 mV). At -20 mV, the large majority (>70%) of Ca²⁺ channel first openings occurred with an estimated delay of about 50 μs in physiological conditions, with a mean open time of 0.5 ms. Similar to other ribbon synapses, Ca²⁺ channels in IHCs showed a low mean open probability (0.21 at -20 mV), but this increased significantly (up to 0.91) when Ca²⁺ channel activity switched to a bursting modality. We propose that IHC Ca²⁺ channels are sufficiently rapid to transmit fast signals of sound onset and support phase-locking. Short-latency Ca²⁺ channel opening coupled to multivesicular release would ensure precise and reliable signal transmission at the IHC ribbon synapse.

The Sodium-Activated Potassium Channel Slack Is Required for Optimal Cognitive Flexibility in Mice

Science.gov (United States)

Bausch, Anne E.; Dieter, Rebekka; Nann, Yvette; Hausmann, Mario; Meyerdierks, Nora; Kaczmarek, Leonard K.; Ruth, Peter; Lukowski, Robert

2015-01-01

"Kcnt1" encoded sodium-activated potassium channels (Slack channels) are highly expressed throughout the brain where they modulate the firing patterns and general excitability of many types of neurons. Increasing evidence suggests that Slack channels may be important for higher brain functions such as cognition and normal intellectual…

Ca²⁺-dependent K⁺ channels in exocrine salivary glands.

Science.gov (United States)

Catalán, Marcelo A; Peña-Munzenmayer, Gaspar; Melvin, James E

2014-06-01

In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function, including salivary glands. Among these proteins, Ca(2+)-dependent K(+) channels take part in key functions including membrane potential regulation, fluid movement and K(+) secretion in exocrine glands. Two K(+) channels have been identified in exocrine salivary glands: (1) a Ca(2+)-activated K(+) channel of intermediate single channel conductance encoded by the KCNN4 gene, and (2) a voltage- and Ca(2+)-dependent K(+) channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca(2+)-dependent K(+) channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca(2+)-dependent K(+) channels by protein-protein interactions that may significantly impact exocrine gland physiology. Published by Elsevier Ltd.

Investigation of one-dimensional interfacial area transport for vertical upward air–water two-phase flow in an annular channel at elevated pressures

International Nuclear Information System (INIS)

Ozar, B.; Brooks, C.S.; Euh, D.J.; Hibiki, T.; Ishii, M.

2013-01-01

Highlights: • Interfacial area transport equation (IATE) for a rectangular duct is modified for an annulus. • IATE predicts interfacial area transport in bubbly-to-churn flow. • Scalability of IATE to elevated pressure conditions is validated. • Detailed 1D interfacial area transport data are presented. • Detailed interfacial area transport mechanisms are discussed. -- Abstract: The interfacial area transport of vertical, upward, air–water two-phase flows in an annular channel has been investigated at different system pressures. The inner and outer diameters of the annular channel were 19.1 mm and 38.1 mm, respectively. Twenty three inlet flow conditions were selected, which covered bubbly, cap-bubbly, and churn-turbulent flows. These flow conditions also overlapped with twelve conditions of a previous study for comparison. The local flow parameters, such as void fractions, interfacial area concentrations (IAC), and bubble interface velocities, were measured at nine radial positions for the three axial locations and converted into area-averaged parameters. The axial evolutions of local flow structure were interpreted in terms of bubble coalescence, breakup, expansion of the gas-phase due to pressure drop and system pressure. An assessment of interfacial area transport equation (IATE) was made and compared with the experimental data. A discussion of the comparison between model prediction and the experimental results were made

Investigation of one-dimensional interfacial area transport for vertical upward air–water two-phase flow in an annular channel at elevated pressures

Energy Technology Data Exchange (ETDEWEB)

Ozar, B., E-mail: ozar@fauske.com [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47907-2017 (United States); Brooks, C.S. [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47907-2017 (United States); Euh, D.J. [Korea Atomic Energy Research Institute, 150 Deokjin, Yuseong, Daejeon 305-353 (Korea, Republic of); Hibiki, T.; Ishii, M. [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47907-2017 (United States)

2013-10-15

Highlights: • Interfacial area transport equation (IATE) for a rectangular duct is modified for an annulus. • IATE predicts interfacial area transport in bubbly-to-churn flow. • Scalability of IATE to elevated pressure conditions is validated. • Detailed 1D interfacial area transport data are presented. • Detailed interfacial area transport mechanisms are discussed. -- Abstract: The interfacial area transport of vertical, upward, air–water two-phase flows in an annular channel has been investigated at different system pressures. The inner and outer diameters of the annular channel were 19.1 mm and 38.1 mm, respectively. Twenty three inlet flow conditions were selected, which covered bubbly, cap-bubbly, and churn-turbulent flows. These flow conditions also overlapped with twelve conditions of a previous study for comparison. The local flow parameters, such as void fractions, interfacial area concentrations (IAC), and bubble interface velocities, were measured at nine radial positions for the three axial locations and converted into area-averaged parameters. The axial evolutions of local flow structure were interpreted in terms of bubble coalescence, breakup, expansion of the gas-phase due to pressure drop and system pressure. An assessment of interfacial area transport equation (IATE) was made and compared with the experimental data. A discussion of the comparison between model prediction and the experimental results were made.

Modelling of activity transport in PHWR

International Nuclear Information System (INIS)

Veena, S.N.; Rangarajan, S.; Narasimhan, S.V.; Horvath, G.L.

2000-01-01

The modelling of mass and activity transport in PHWR is of importance in predicting the build up of radiation field in and around the Primary Heat Transport system which will consequently help in planning the Dilute Chemical Decontamination and man rem budgeting. Modeling also helps in understanding the different parameters controlling the transport behaviour. Some of the important parameters include coolant chemistry like pH, physical parameters like temperature, the nature of the corrosion film and hence the effect of passivation techniques. VVER code for activity transport uses six nodes for the primary system and is essentially devised for stainless steel system. In the present work though based on this model, major modifications have been incorporated to suit the PHWR conditions. In the code, the PHT system of PHWR is suitably divided into 14 nodes, 5 in-core and 9 out of core nodes based on material and heat transfer properties. This paper describes the mechanisms involved in the various processes like generation of corrosion products, their release as well as their transport into the primary coolant, the activation of inactive corrosion product nuclides and the build up of radiation field due to 60 Co around the PHT system. (author)

The Function of the Novel Mechanical Activated Ion Channel Piezo1 in the Human Osteosarcoma Cells

OpenAIRE

Jiang, Long; Zhao, Yi-ding; Chen, Wei-xiang

2017-01-01

Background The Piezo1 protein ion channel is a novel mechanical activated ion channel which is related to mechanical signal transduction. However, the function of the mechanically activated ion channel Piezo1 had not been explored. In this study, we explored the function of the Piezo1 ion channel in human osteosarcoma (OS) cells related to apoptosis, invasion, and the cell proliferation. Material/Methods Reverse transcription polymerase chain reaction (RT-PCR) and western-blotting were used t...

Molecular properties of mammalian proteins that interact with cGMP: protein kinases, cation channels, phosphodiesterases, and multi-drug anion transporters.

Science.gov (United States)

Francis, Sharron H; Blount, Mitsi A; Zoraghi, Roya; Corbin, Jackie D

2005-09-01

Cyclic GMP is a critical second messenger signaling molecule in many mammalian cell types. It is synthesized by a family of guanylyl cyclases that is activated in response to stimuli from hormones such as natriuretic peptides, members of the guanylin family, and chemical stimuli including nitric oxide and carbon monoxide. The resulting elevation of cGMP modulates myriad physiological processes. Three major groups of cellular proteins bind cGMP specifically at allosteric sites; interaction of cGMP with these sites modulates the activities and functions of other domains within these protein groups to bring about physiological effects. These proteins include the cyclic nucleotide (cN)-dependent protein kinases, cN-gated cation channels, and cGMP-binding phosphodiesterases (PDE). Cyclic GMP also interacts with the catalytic sites of many cN PDEs and with some members of the multi-drug anion transporter family (MRPs) which can extrude nucleotides from cells. The allosteric cN-binding sites in the kinases and the cN-gated channels are evolutionarily and biochemically related, whereas the allosteric cGMP-binding sites in PDEs (also known as GAF domains), the catalytic sites of PDEs , and the ligand-binding sites in the MRPs are evolutionarily and biochemically distinct from each other and from those in the kinase and channel families. The sites that interact with cGMP within each of these groups of proteins have unique properties that provide for cGMP binding. Within a given cell, cGMP can potentially interact with members of all these groups of proteins if they are present. The relative abundance and affinities of these various cGMP-binding sites in conjunction with their subcellular compartmentation, proximity to cyclases and PDEs, and post-translational modification contribute importantly in determining the impact of these respective proteins to cGMP signaling within a particular cell.

MRP transporters as membrane machinery in the bradykinin-inducible export of ATP.

Science.gov (United States)

Zhao, Yumei; Migita, Keisuke; Sun, Jing; Katsuragi, Takeshi

2010-04-01

Adenosine triphosphate (ATP) plays the role of an autocrine/paracrine signal molecule in a variety of cells. So far, however, the membrane machinery in the export of intracellular ATP remains poorly understood. Activation of B2-receptor with bradykinin-induced massive release of ATP from cultured taenia coli smooth muscle cells. The evoked release of ATP was unaffected by gap junction hemichannel blockers, such as 18alpha-glycyrrhetinic acid and Gap 26. Furthermore, the cystic fibrosis transmembrane regulator (CFTR) coupled Cl(-) channel blockers, CFTR(inh)172, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, Gd3(+) and glibenclamide, failed to suppress the export of ATP by bradykinin. On the other, the evoked release of ATP was greatly reduced by multidrug resistance protein (MRP) transporter inhibitors, MK-571, indomethacin, and benzbromarone. From western blotting analysis, blots of MRP 1 protein only, but not MRP 2 and MRP 3 protein, appeared at 190 kD. However, the MRP 1 protein expression was not enhanced after loading with 1 muM bradykinin for 5 min. Likewise, niflumic acid and fulfenamic acid, Ca2(+)-activated Cl(-) channel blockers, largely abated the evoked release of ATP. The possibility that the MRP transporter system couples with Ca2(+)-activated Cl(-) channel activities is discussed here. These findings suggest that MRP transporters, probably MRP 1, unlike CFTR-Cl(-) channels and gap junction hemichannels, may contribute as membrane machinery to the export of ATP induced by G-protein-coupled receptor stimulation.

An active matter analysis of intracellular Active Transport

Science.gov (United States)

Wang, Bo; Chen, Kejia; Bae, Sung Chul; Granick, Steve

2012-02-01

Tens of thousands of fluorescence-based trajectories at nm resolution have been analyzed, regarding active transport along microtubules in living cells. The following picture emerges. Directed motion to pre-determined locations is certainly an attractive idea, but cannot be pre-programmed as to do so would sacrifice adaptability. The polarity of microtubules is inadequate to identify these directions in cells, and no other mechanism is currently known. We conclude that molecular motors carry cargo through disordered intracellular microtubule networks in a statistical way, with loud cellular ``noise'' both in directionality and speed. Programmed random walks describe how local 1D active transport traverses crowded cellular space efficiently, rapidly, minimizing the energy waste that would result from redundant activity. The mechanism of statistical regulation is not yet understood, however.

Ethanol affects network activity in cultured rat hippocampus: mediation by potassium channels.

Directory of Open Access Journals (Sweden)

Eduard Korkotian

Full Text Available The effects of ethanol on neuronal network activity were studied in dissociated cultures of rat hippocampus. Exposure to low (0.25-0.5% ethanol concentrations caused an increase in synchronized network spikes, and a decrease in the duration of individual spikes. Ethanol also caused an increase in rate of miniature spontaneous excitatory postsynaptic currents. Higher concentrations of ethanol eliminated network spikes. These effects were reversible upon wash. The effects of the high, but not the low ethanol were blocked by the GABA antagonist bicuculline. The enhancing action of low ethanol was blocked by apamin, an SK potassium channel antagonist, and mimicked by 1-EBIO, an SK channel opener. It is proposed that in cultured hippocampal networks low concentration of ethanol is associated with SK channel activity, rather than the GABAergic receptor.

Estimating changes in riparian and channel features along the Trinity River downstream of Lewiston Dam, California, 1980 to 2011

Science.gov (United States)

Curtis, Jennifer A.

2015-01-01

Dam construction, flow diversion, and legacy landuse effects reduced the transport capacity, sediment supply, channel complexity and floodplain-connectivity along the Trinity River, CA below Lewiston Dam. This study documents the geomorphic evolution of the Trinity River Restoration Program’s intensively managed 65-km long restoration reach from 1980 to 2011. The nature and extent of riparian and channel changes were assessed using a series of geomorphic feature maps constructed from ortho-rectified photography acquired at low flow conditions in 1980, 1997, 2001, 2006, 2009, and 2011. Since 1980 there has been a general conversion of riparian to channel features and expansion of the active channel area. The primary mechanism for expansion of the active channel was bank erosion from 1980 to 1997 and channel widening was well distributed longitudinally throughout the study reach. Subsequent net bar accretion from 1997 to 2001, followed by slightly higher net bar scour from 2001 to 2006, occurred primarily in the central and lower reaches of the study area. In comparison, post-2006 bank and bar changes were spatially-limited to reaches with sufficient local transport capacity or sediment supply supported by gravel augmentation, mechanical channel rehabilitation, and tributary contributions to flow and sediment supply. A series of tributary floods in 1997, 1998 and 2006 were the primary factors leading to documented increases in channel complexity and floodplain connectivity. During the post-2006 period managed flow releases, in the absence of large magnitude tributary flooding, combined with gravel augmentation and mechanical restoration caused localized increases in sediment supply and transport capacity leading to smaller but measurable increases in channel complexity and floodplain connectivity primarily in the upper river below Lewiston Dam.

The effect of a concentration-dependent viscosity on particle transport in a channel flow with porous walls

KAUST Repository

Herterich, James G.

2014-02-02

The transport of a dilute suspension of particles through a channel with porous walls, accounting for the concentration dependence of the viscosity, is analyzed. In particular, we study two cases of fluid permeation through the porous channel walls: (1) at a constant flux and (2) dependent on the pressure drop across the wall. We also consider the effect of mixing the suspension first compared with point injection by considering inlet concentration distributions of different widths. We find that a pessimal inlet distribution width exists that maximizes the required hydrodynamic pressure for a constant fluid influx. The effect of an external hydrodynamic pressure, to compensate for the reduced transmembrane pressure difference due to osmotic pressure, is investigated. © 2014 American Institute of Chemical Engineers.

The antipsychotic drug loxapine is an opener of the sodium-activated potassium channel slack (Slo2.2).

Science.gov (United States)

Biton, B; Sethuramanujam, S; Picchione, Kelly E; Bhattacharjee, A; Khessibi, N; Chesney, F; Lanneau, C; Curet, O; Avenet, P

2012-03-01

Sodium-activated potassium (K(Na)) channels have been suggested to set the resting potential, to modulate slow after-hyperpolarizations, and to control bursting behavior or spike frequency adaptation (Trends Neurosci 28:422-428, 2005). One of the genes that encodes K(Na) channels is called Slack (Kcnt1, Slo2.2). Studies found that Slack channels were highly expressed in nociceptive dorsal root ganglion neurons and modulated their firing frequency (J Neurosci 30:14165-14172, 2010). Therefore, Slack channel openers are of significant interest as putative analgesic drugs. We screened the library of pharmacologically active compounds with recombinant human Slack channels expressed in Chinese hamster ovary cells, by using rubidium efflux measurements with atomic absorption spectrometry. Riluzole at 500 μM was used as a reference agonist. The antipsychotic drug loxapine and the anthelmintic drug niclosamide were both found to activate Slack channels, which was confirmed by using manual patch-clamp analyses (EC(50) = 4.4 μM and EC(50) = 2.9 μM, respectively). Psychotropic drugs structurally related to loxapine were also evaluated in patch-clamp experiments, but none was found to be as active as loxapine. Loxapine properties were confirmed at the single-channel level with recombinant rat Slack channels. In dorsal root ganglion neurons, loxapine was found to behave as an opener of native K(Na) channels and to increase the rheobase of action potential. This study identifies new K(Na) channel pharmacological tools, which will be useful for further Slack channel investigations.

Purinergic regulation of CFTR and Ca²⁺ -activated C^l- channels and K⁺ channels in human pancreatic duct epithelium

DEFF Research Database (Denmark)

Wang, Jing; Haanes, Kristian A; Novak, Ivana

2013-01-01

mutated CFTR, basolateral ATP and UTP had negligible effects. In addition to Cl(-) transport in Capan-1 cells, the effects of 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (DC-EBIO) and clotrimazole indicated functional expression of the intermediate conductance K(+) channels (IK, KCa3...

Phosphatidylinositol (4,5)bisphosphate inhibits K+-efflux channel activity in NT1 tobacco cultured cells.

Science.gov (United States)

Ma, Xiaohong; Shor, Oded; Diminshtein, Sofia; Yu, Ling; Im, Yang Ju; Perera, Imara; Lomax, Aaron; Boss, Wendy F; Moran, Nava

2009-02-01

In the animal world, the regulation of ion channels by phosphoinositides (PIs) has been investigated extensively, demonstrating a wide range of channels controlled by phosphatidylinositol (4,5)bisphosphate (PtdInsP2). To understand PI regulation of plant ion channels, we examined the in planta effect of PtdInsP2 on the K+-efflux channel of tobacco (Nicotiana tabacum), NtORK (outward-rectifying K channel). We applied a patch clamp in the whole-cell configuration (with fixed "cytosolic" Ca2+ concentration and pH) to protoplasts isolated from cultured tobacco cells with genetically manipulated plasma membrane levels of PtdInsP2 and cellular inositol (1,4,5)trisphosphate: "Low PIs" had depressed levels of these PIs, and "High PIs" had elevated levels relative to controls. In all of these cells, K channel activity, reflected in the net, steady-state outward K+ currents (IK), was inversely related to the plasma membrane PtdInsP2 level. Consistent with this, short-term manipulations decreasing PtdInsP2 levels in the High PIs, such as pretreatment with the phytohormone abscisic acid (25 microM) or neutralizing the bath solution from pH 5.6 to pH 7, increased IK (i.e. NtORK activity). Moreover, increasing PtdInsP2 levels in controls or in abscisic acid-treated high-PI cells, using the specific PI-phospholipase C inhibitor U73122 (2.5-4 microM), decreased NtORK activity. In all cases, IK decreases stemmed largely from decreased maximum attainable NtORK channel conductance and partly from shifted voltage dependence of channel gating to more positive potentials, making it more difficult to activate the channels. These results are consistent with NtORK inhibition by the negatively charged PtdInsP2 in the internal plasma membrane leaflet. Such effects are likely to underlie PI signaling in intact plant cells.

Health Impacts of Active Transportation in Europe.

Science.gov (United States)

Rojas-Rueda, David; de Nazelle, Audrey; Andersen, Zorana J; Braun-Fahrländer, Charlotte; Bruha, Jan; Bruhova-Foltynova, Hana; Desqueyroux, Hélène; Praznoczy, Corinne; Ragettli, Martina S; Tainio, Marko; Nieuwenhuijsen, Mark J

2016-01-01

Policies that stimulate active transportation (walking and bicycling) have been related to heath benefits. This study aims to assess the potential health risks and benefits of promoting active transportation for commuting populations (age groups 16-64) in six European cities. We conducted a health impact assessment using two scenarios: increased cycling and increased walking. The primary outcome measure was all-cause mortality related to changes in physical activity level, exposure to fine particulate matter air pollution with a diameter Paris, Prague, and Warsaw. All scenarios produced health benefits in the six cities. An increase in bicycle trips to 35% of all trips (as in Copenhagen) produced the highest benefits among the different scenarios analysed in Warsaw 113 (76-163) annual deaths avoided, Prague 61 (29-104), Barcelona 37 (24-56), Paris 37 (18-64) and Basel 5 (3-9). An increase in walking trips to 50% of all trips (as in Paris) resulted in 19 (3-42) deaths avoided annually in Warsaw, 11(3-21) in Prague, 6 (4-9) in Basel, 3 (2-6) in Copenhagen and 3 (2-4) in Barcelona. The scenarios would also reduce carbon dioxide emissions in the six cities by 1,139 to 26,423 (metric tonnes per year). Policies to promote active transportation may produce health benefits, but these depend of the existing characteristics of the cities. Increased collaboration between health practitioners, transport specialists and urban planners will help to introduce the health perspective in transport policies and promote active transportation.

Quantification and distribution of big conductance Ca2+-activated K+ channels in kidney epithelia

DEFF Research Database (Denmark)

Grunnet, Morten; Hay-Schmidt, Anders; Klaerke, Dan A

2005-01-01

and immunohistochemical studies. In cortical collecting ducts, BK channels were exclusively located in principal cells while no channels could be found in intercalated cells. The abundant and distinct distribution in kidney epithelia talks in favor for BK channels being important contributors in maintaining salt......Big conductance Ca2+ activated K+ channels (BK channels) is an abundant channel present in almost all kind of tissue. The accurate quantity and especially the precise distribution of this channel in kidney epithelia are, however, still debated. The aim of the present study has therefore been...... to examine the presence of BK channels in kidney epithelia and determine the actual number and distribution of these channels. For this purpose, a selective peptidyl ligand for BK channels called iberiotoxin or the radiolabeled double mutant analog 125I-IbTX-D19Y/Y36F has been employed. The presence of BK...

Ion channel activity of membrane vesicles released from sea urchin sperm during the acrosome reaction

International Nuclear Information System (INIS)

Schulz, Joseph R.; Vega-Beltran, Jose L. de la; Beltran, Carmen; Vacquier, Victor D.; Darszon, Alberto

2004-01-01

The sperm acrosome reaction (AR) involves ion channel activation. In sea urchin sperm, the AR requires Ca 2+ and Na + influx and K + and H + efflux. During the AR, the plasma membrane fuses with the acrosomal vesicle membrane forming hybrid membrane vesicles that are released from sperm into the medium. This paper reports the isolation and preliminary characterization of these acrosome reaction vesicles (ARVs), using synaptosome-associated protein of 25 kDa (SNAP-25) as a marker. Isolated ARVs have a unique protein composition. The exocytosis regulatory proteins vesicle-associated membrane protein and SNAP-25 are inside ARVs, as judged by protease protection experiments, and membrane associated based on Triton X-114 partitioning. ARVs fused with planar bilayers display three main types of single channel activity. The most frequently recorded channel is cationic, weakly voltage dependent and has a low open probability that increases with negative potentials. This channel is activated by cAMP, blocked by Ba 2+ , and has a PK + /PNa + selectivity of 4.5. ARVs represent a novel membrane preparation suitable to deepen our understanding of ion channel activity in the AR and during fertilization

Mechanosensitive channels are activated by stress in the actin stress fibres, and could be involved in gravity sensing in plants.

Science.gov (United States)

Tatsumi, H; Furuichi, T; Nakano, M; Toyota, M; Hayakawa, K; Sokabe, M; Iida, H

2014-01-01

Mechanosensitive (MS) channels are expressed in a variety of cells. The molecular and biophysical mechanism involved in the regulation of MS channel activities is a central interest in basic biology. MS channels are thought to play crucial roles in gravity sensing in plant cells. To date, two mechanisms have been proposed for MS channel activation. One is that tension development in the lipid bilayer directly activates MS channels. The second mechanism proposes that the cytoskeleton is involved in the channel activation, because MS channel activities are modulated by pharmacological treatments that affect the cytoskeleton. We tested whether tension in the cytoskeleton activates MS channels. Mammalian endothelial cells were microinjected with phalloidin-conjugated beads, which bound to stress fibres, and a traction force to the actin cytoskeleton was applied by dragging the beads with optical tweezers. MS channels were activated when the force was applied, demonstrating that a sub-pN force to the actin filaments activates a single MS channel. Plants may use a similar molecular mechanism in gravity sensing, since the cytoplasmic Ca(2+) concentration increase induced by changes in the gravity vector was attenuated by potential MS channel inhibitors, and by actin-disrupting drugs. These results support the idea that the tension increase in actin filaments by gravity-dependent sedimentation of amyloplasts activates MS Ca(2+) -permeable channels, which can be the molecular mechanism of a Ca(2+) concentration increase through gravistimulation. We review recent progress in the study of tension sensing by actin filaments and MS channels using advanced biophysical methods, and discuss their possible roles in gravisensing. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Chamber transport for heavy ion fusion

International Nuclear Information System (INIS)

Olson, Craig L.

2014-01-01

A brief review is given of research on chamber transport for HIF (heavy ion fusion) dating from the first HIF Workshop in 1976 to the present. Chamber transport modes are categorized into ballistic transport modes and channel-like modes. Four major HIF reactor studies are summarized (HIBALL-II, HYLIFE-II, Prometheus-H, OSIRIS), with emphasis on the chamber transport environment. In general, many beams are used to provide the required symmetry and to permit focusing to the required small spots. Target parameters are then discussed, with a summary of the individual heavy ion beam parameters required for HIF. The beam parameters are then classified as to their line charge density and perveance, with special emphasis on the perveance limits for radial space charge spreading, for the space charge limiting current, and for the magnetic (Alfven) limiting current. The major experiments on ballistic transport (SFFE, Sabre beamlets, GAMBLE II, NTX, NDCX) are summarized, with specific reference to the axial electron trapping limit for charge neutralization. The major experiments on channel-like transport (GAMBLE II channel, GAMBLE II self-pinch, LBNL channels, GSI channels) are discussed. The status of current research on HIF chamber transport is summarized, and the value of future NDCX-II transport experiments for the future of HIF is noted

Fun at Antarctic grounding lines: Ice-shelf channels and sediment transport

Science.gov (United States)

Drews, Reinhard; Mayer, Christoph; Eisen, Olaf; Helm, Veit; Ehlers, Todd A.; Pattyn, Frank; Berger, Sophie; Favier, Lionel; Hewitt, Ian H.; Ng, Felix; Fürst, Johannes J.; Gillet-Chaulet, Fabien; Bergeot, Nicolas; Matsuoka, Kenichi

2017-04-01

Meltwater beneath the polar ice sheets drains, in part, through subglacial conduits. Landforms created by such drainages are abundant in areas formerly covered by ice sheets during the last glacial maximum. However, observations of subglacial conduit dynamics under a contemporary ice sheet are lacking. We present results from ice-penetrating radar to infer the existence of subglacial conduits upstream of the grounding line of Roi Baudouin Ice Shelf, Antarctica. The conduits are aligned with ice-shelf channels, and underlain by esker ridges formed from sediment deposition due to reduced water outflow speed near the grounding line. In turn, the eskers modify local ice flow to initiate the bottom topography of the ice-shelf channels, and create small surface ridges extending onto the shelf. Relict features on the shelf are interpreted to indicate a history of these interactions and variability of past subglacial drainages. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation, and ice-shelf stability. To investigate the role of sediment transport beneath ice sheets further, we model the sheet-shelf system of the Ekstömisen catchment, Antarctica. A 3D finite element model (Elmer/ICE) is used to solve the transients full Stokes equation for isotropic, isothermal ice with a dynamic grounding line. We initialize the model with surface topography from the TanDEM-X satellites and by inverting simultaneously for ice viscosity and basal drag using present-day surface velocities. Results produce a flow field which is consitent with sattelite and on-site observations. Solving the age-depth relationship allows comparison with radar isochrones from airborne data, and gives information about the atmospheric/dynamic history of this sector. The flow field will eventually be used to identify potential sediment sources and sinks which we compare with more than 400 km of

Effects of a Danish multicomponent physical activity intervention on active school transport

DEFF Research Database (Denmark)

Breum, Lars; Toftager, Mette; Ersbøll, Annette K.

2014-01-01

activity, active transport and after-school fitness program. Transport mode to school was assessed through a 5-day transportation diary. Results The proportion of active transport was high at baseline (86.0%) and was maintained at the two-year follow-up (87.0%). There was no difference in active travel...... between the intervention and the comparison schools after the intervention, but more students perceived parental encouragement and had a positive attitude towards bicycling at the intervention schools. This difference was however only borderline significant. Conclusion The prevalence of AST was high...... at both baseline and follow-up, but no difference between the intervention and comparison schools was detected. Future intervention research should ensure a high degree of involvement of students, teachers and parents, focus merely on AST and take advantage of already planned physical environment changes...

Sedimentary processes of the lower Monterey Fan channel and channel-mouth lobe

Science.gov (United States)

Klaucke, I.; Masson, D.G.; Kenyon, Neil H.; Gardner, J.V.

2004-01-01

The distribution of deposits, sediment transport pathways and processes on the lower Monterey Fan channel and channel-mouth lobe (CML) are studied through the integration of GLORIA and TOBI sidescan sonar data with 7-kHz subbottom profiler records and sediment cores for ground-truthing. The lower Monterey channel is characterised by an up to 30-m-deep channel with poorly developed levees and alternating muddy and silty muddy overbank deposits. The channel is discontinuous, disappearing where gradients are less than about 1:350. Ground-truthing of the large CML shows that the entire CML is characterised by widespread deposits of generally fine sand, with coarser sand at the base of turbidites. Sand is particularly concentrated in finger-like areas of low-backscatter intensity and is interpreted as the result of non-turbulent sediment-gravity flows depositing metres thick massive, fine sand. TOBI sidescan sonar data reveal recent erosional features in the form of scours, secondary channels, large flow slides, and trains of blocks at the distal end of the CML. Erosion is probably related to increasing gradient as the CML approaches Murray Fracture zone and to differential loading of sandy submarine fan deposits onto pelagic clays. Reworking of older flow slides by sediment transport processes on the lobe produces trains of blocks that are several metres in diameter and aligned parallel to the flow direction. ?? 2004 Elsevier B.V. All rights reserved.

Active Dendrites and Differential Distribution of Calcium Channels Enable Functional Compartmentalization of Golgi Cells.

Science.gov (United States)

Rudolph, Stephanie; Hull, Court; Regehr, Wade G

2015-11-25

Interneurons are essential to controlling excitability, timing, and synaptic integration in neuronal networks. Golgi cells (GoCs) serve these roles at the input layer of the cerebellar cortex by releasing GABA to inhibit granule cells (grcs). GoCs are excited by mossy fibers (MFs) and grcs and provide feedforward and feedback inhibition to grcs. Here we investigate two important aspects of GoC physiology: the properties of GoC dendrites and the role of calcium signaling in regulating GoC spontaneous activity. Although GoC dendrites are extensive, previous studies concluded they are devoid of voltage-gated ion channels. Hence, the current view holds that somatic voltage signals decay passively within GoC dendrites, and grc synapses onto distal dendrites are not amplified and are therefore ineffective at firing GoCs because of strong passive attenuation. Using whole-cell recording and calcium imaging in rat slices, we find that dendritic voltage-gated sodium channels allow somatic action potentials to activate voltage-gated calcium channels (VGCCs) along the entire dendritic length, with R-type and T-type VGCCs preferentially located distally. We show that R- and T-type VGCCs located in the dendrites can boost distal synaptic inputs and promote burst firing. Active dendrites are thus critical to the regulation of GoC activity, and consequently, to the processing of input to the cerebellar cortex. In contrast, we find that N-type channels are preferentially located near the soma, and control the frequency and pattern of spontaneous firing through their close association with calcium-activated potassium (KCa) channels. Thus, VGCC types are differentially distributed and serve specialized functions within GoCs. Interneurons are essential to neural processing because they modulate excitability, timing, and synaptic integration within circuits. At the input layer of the cerebellar cortex, a single type of interneuron, the Golgi cell (GoC), carries these functions. The

Investigation of thermal energy transport from an anisotropic central heating element to the adjacent channels: A multipoint flux approximation

KAUST Repository

Salama, Amgad

2015-02-01

The problem of heat transfer from a central heating element pressed between two clad plates to cooling channels adjacent and outboard of the plates is investigated numerically. The aim of this work is to highlight the role of thermal conductivity anisotropy of the heating element and/or the encompassing plates on thermal energy transport to the fluid passing through the two channels. When the medium is anisotropic with respect to thermal conductivity; energy transport to the neighboring channels is no longer symmetric. This asymmetry in energy fluxes influence heat transfer to the coolant resulting in different patterns of temperature fields. In particular, it is found that the temperature fields are skewed towards the principal direction of anisotropy. In addition, the heat flux distributions along the edges of the heating element are also different as a manifestation of thermal conductivity anisotropy. Furthermore, the peak temperature at the channel walls change location and magnitude depending on the principal direction of anisotropy. Based on scaling arguments, it is found that, the ratio of width to the height of the heating system is a key parameter which can suggest when one may ignore the effect of the cross-diagonal terms of the full conductivity tensor. To account for anisotropy in thermal conductivity, the method of multipoint flux approximation (MPFA) is employed. Using this technique, it is possible to find a finite difference stencil which can handle full thermal conductivity tensor and in the same time enjoys the simplicity of finite difference approximation. Although the finite difference stencil based on MPFA is quite complex, in this work we apply the recently introduced experimenting field approach which construct the global problem automatically.

Debris-flow activity in abandoned channels of the Manival torrent reconstructed with LiDAR and tree-ring data

Directory of Open Access Journals (Sweden)

J. Lopez Saez

2011-05-01

Full Text Available Hydrogeomorphic processes are a major threat in many parts of the Alps, where they periodically damage infrastructure, disrupt transportation corridors or even cause loss of life. Nonetheless, past torrential activity and the analysis of areas affected during particular events remain often imprecise. It was therefore the purpose of this study to reconstruct spatio-temporal patterns of past debris-flow activity in abandoned channels on the forested cone of the Manival torrent (Massif de la Chartreuse, French Prealps. A Light Detecting and Ranging (LiDAR generated Digital Elevation Model (DEM was used to identify five abandoned channels and related depositional forms (lobes, lateral levees in the proximal alluvial fan of the torrent. A total of 156 Scots pine trees (Pinus sylvestris L. with clear signs of debris flow events was analyzed and growth disturbances (GD assessed, such as callus tissue, the onset of compression wood or abrupt growth suppression. In total, 375 GD were identified in the tree-ring samples, pointing to 13 debris-flow events for the period 1931–2008. While debris flows appear to be very common at Manival, they have only rarely propagated outside the main channel over the past 80 years. Furthermore, analysis of the spatial distribution of disturbed trees contributed to the identification of four patterns of debris-flow routing and led to the determination of three preferential breakout locations. Finally, the results of this study demonstrate that the temporal distribution of debris flows did not exhibit significant variations since the beginning of the 20th century.

Activation of human IK and SK Ca2+ -activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime)

DEFF Research Database (Denmark)

Strøbaek, Dorte; Teuber, Lene; Jørgensen, Tino D

2004-01-01

We have identified and characterized the compound NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) as a potent activator of human Ca2+ -activated K+ channels of SK and IK types, whereas it is devoid of effect on BK type channels. IK- and SK-channels have previously been reported to be activated...

Ca2+ Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca2+-Dependent Nuclear Gene Expression

Directory of Open Access Journals (Sweden)

Krishna Samanta

2015-07-01

Full Text Available In polarized cells or cells with complex geometry, clustering of plasma-membrane (PM ion channels is an effective mechanism for eliciting spatially restricted signals. However, channel clustering is also seen in cells with relatively simple topology, suggesting it fulfills a more fundamental role in cell biology than simply orchestrating compartmentalized responses. Here, we have compared the ability of store-operated Ca2+ release-activated Ca2+ (CRAC channels confined to PM microdomains with a similar number of dispersed CRAC channels to activate transcription factors, which subsequently increase nuclear gene expression. For similar levels of channel activity, we find that channel confinement is considerably more effective in stimulating gene expression. Our results identify a long-range signaling advantage to the tight evolutionary conservation of channel clustering and reveal that CRAC channel aggregation increases the strength, fidelity, and reliability of the general process of excitation-transcription coupling.

Spin magneto-transport in a Rashba-Dresselhaus quantum channel with single and double finger gates

Science.gov (United States)

Tang, Chi-Shung; Keng, Jia-An; Abdullah, Nzar Rauf; Gudmundsson, Vidar

2017-05-01

We address spin-resolved electronic transport properties in a Rashba-Dresselhaus quantum channel in the presence of an in-plane magnetic field. The strong Rashba-Dresselhaus effect induces an asymmetric spin-splitting energy spectrum with a spin-orbit-Zeeman gap. This asymmetric fact in energy spectrum may result in various quantum dynamic features in conductance due to the presence of finger gates. This asymmetric spin-splitting energy spectrum results in a bound state in continuum for electrons within ultralow energy regime with binding energies in order of 10-1 meV.

Health Impacts of Active Transportation in Europe.

Directory of Open Access Journals (Sweden)

David Rojas-Rueda

Full Text Available Policies that stimulate active transportation (walking and bicycling have been related to heath benefits. This study aims to assess the potential health risks and benefits of promoting active transportation for commuting populations (age groups 16-64 in six European cities. We conducted a health impact assessment using two scenarios: increased cycling and increased walking. The primary outcome measure was all-cause mortality related to changes in physical activity level, exposure to fine particulate matter air pollution with a diameter <2.5 μm, as well as traffic fatalities in the cities of Barcelona, Basel, Copenhagen, Paris, Prague, and Warsaw. All scenarios produced health benefits in the six cities. An increase in bicycle trips to 35% of all trips (as in Copenhagen produced the highest benefits among the different scenarios analysed in Warsaw 113 (76-163 annual deaths avoided, Prague 61 (29-104, Barcelona 37 (24-56, Paris 37 (18-64 and Basel 5 (3-9. An increase in walking trips to 50% of all trips (as in Paris resulted in 19 (3-42 deaths avoided annually in Warsaw, 11(3-21 in Prague, 6 (4-9 in Basel, 3 (2-6 in Copenhagen and 3 (2-4 in Barcelona. The scenarios would also reduce carbon dioxide emissions in the six cities by 1,139 to 26,423 (metric tonnes per year. Policies to promote active transportation may produce health benefits, but these depend of the existing characteristics of the cities. Increased collaboration between health practitioners, transport specialists and urban planners will help to introduce the health perspective in transport policies and promote active transportation.

A Hot Knife Through Ice-Cream: Earthflow Response to Channel Incision (Or Channel Response to Earthflows?), Eel River Canyon, California

Science.gov (United States)

Mackey, B. H.; Roering, J. J.; McKean, J. A.

2007-12-01

Abundant glacier-like earthflow features are recognized as a primary erosional process in the highly erodable Franciscan Melange of the Eel River Basin, CA. Despite their prominence in this "melting ice-cream" topography, many questions regarding their effects on the long term sediment flux from this rapidly eroding basin remain unresolved. For example, does an earthflow's basal shear zone propagate vertically downwards with vertical river incision? What controls the upslope and lateral extent of individual earthflows? How does the erosive power of a river influence the rate of earthflow movement, or conversely do earthflow toe deposits regulate the rate of river incision? Here we present preliminary findings derived from study of 200km2 of lidar data (1m resolution) covering hillslopes adjacent to 30km of the Eel River. Lidar allows detailed analysis of the interaction between earthflows and the drainage network, and we document how inferred changes in local base level are propagated throughout adjacent hillslopes via earthflow movement. The most active earthflows (determined by field surveying and analysis of aerial photos rectified using lidar- generated digital topography) coincide with locally steep sections of channel, while downstream of the most active flows we frequently observe less-active or dormant earthflows. This observation supports the idea that the locations of the most active earthflows coincide with headward propagating knickpoints in the channel. The rate of earthflow movement appears to slow when an earthflow exhausts the upslope area of easily mobilized sediment. Earthflow toes can protrude directly into the channel, causing the channel to narrow and steepen, and even undercut the opposite bank. Large resistant boulders (>2m diameter) transported by the earthflow accumulate in the streambed and appear to both act as a check on further channel incision and earthflow movement. In contrast, areas adjacent to active earthflows exhibit smooth

Final Technical Report Transport Task Force Activities

International Nuclear Information System (INIS)

P.W. Terry

2006-01-01

The Transport Task Force has functioned as the primary scientific organization in the area of magnetic-fusion confinement and transport since its inception in 1988. It has defined and set research directions, coordinated broad research efforts, advocated new funding initiatives, and created a highly successful and widely admired interactive culture between experiment, theory and modeling. The Transport Task Force carries out its activities under the direction of its chair and the Executive Committee. The Executive Committee is comprised of the leaders and deputy leaders of the scientific working groups. The working groups are structured and organized according to research needs and priorities and have been organized around the areas of Core Transport, H Mode and Pedestal, Fast Particle Transport, Transient Transport Phenomena, and Modeling and Simulation. A steering committee provides advise on TTF activities. Further information on the working groups and the structure and management of the TTF can be found at http://psfcwww2.psfc.mit.edu/ttf/index.html. The TTF holds an annual workshop. A summary of the workshops held during the period of this report is given in Appendix I. During the period of this report the Transport Task Force was involved in several significant activities. Foremost of these was a sweeping review of the status of transport science, the key research tasks for progress during the next 5-10 years, and a proposal for a funding initiative to ensure application of adequate resources to these problems. The conclusions of this study were incorporated into a white paper, which is copied below in Appendix II. Other significant activities have included the introduction of an extended, ongoing discussion on verification and validation as a requisite for defining and codifying the path toward predictive capability, the orchestration of a gradual shift of focus from ion thermal confinement to electron thermal confinement, and a joining of efforts on edge

Milrinone-Induced Postconditioning Requires Activation of Mitochondrial Ca2+-sensitive Potassium (mBKCa) Channels

NARCIS (Netherlands)

Behmenburg, Friederike; Trefz, Lara; Dorsch, Marianne; Ströthoff, Martin; Mathes, Alexander; Raupach, Annika; Heinen, André; Hollmann, Markus W.; Berger, Marc M.; Huhn, Ragnar

2017-01-01

Cardioprotection by postconditioning requires activation of mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels. The involvement of these channels in milrinone-induced postconditioning is unknown. The authors determined whether cardioprotection by milrinone-induced

TNF-α promotes cell survival through stimulation of K+ channel and NFκB activity in corneal epithelial cells

International Nuclear Information System (INIS)

Wang Ling; Reinach, Peter; Lu, Luo

2005-01-01

Tumor necrosis factor (TNF-α) in various cell types induces either cell death or mitogenesis through different signaling pathways. In the present study, we determined in human corneal epithelial cells how TNF-α also promotes cell survival. Human corneal epithelial (HCE) cells were cultured in DMEM/F-12 medium containing 10% FBS. TNF-α stimulation induced activation of a voltage-gated K + channel detected by measuring single channel activity using patch clamp techniques. The effect of TNF-α on downstream events included NFκB nuclear translocation and increases in DNA binding activities, but did not elicit ERK, JNK, or p38 limb signaling activation. TNF-α induced increases in p21 expression resulting in partial cell cycle attenuation in the G 1 phase. Cell cycle progression was also mapped by flow cytometer analysis. Blockade of TNF-α-induced K + channel activity effectively prevented NFκB nuclear translocation and binding to DNA, diminishing the cell-survival protective effect of TNF-α. In conclusion, TNF-α promotes survival of HCE cells through sequential stimulation of K + channel and NFκB activities. This response to TNF-α is dependent on stimulating K + channel activity because following suppression of K + channel activity TNF-α failed to activate NFκB nuclear translocation and binding to nuclear DNA

Stream Channel Stability.

Science.gov (United States)

1981-04-01

Cycles of wetting and drying are also t ,v itiue swelling and shrinkage of the soil. S 11ied blocks or peds of soil fabric ,,ks. id downslope soil creep ...hydrographs of water and sediment at the point in question. By feeding the output from the hydrology-transport model into the finite element model...the banks as undercut banks fail. Channel irregularities such as seepage zones, cattle crossings, overbank drainage, buried channels, organic deposits

Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.

Science.gov (United States)

Lin, C S; Boltz, R C; Blake, J T; Nguyen, M; Talento, A; Fischer, P A; Springer, M S; Sigal, N H; Slaughter, R S; Garcia, M L

1993-03-01

The role that potassium channels play in human T lymphocyte activation has been investigated by using specific potassium channel probes. Charybdotoxin (ChTX), a blocker of small conductance Ca(2+)-activated potassium channels (PK,Ca) and voltage-gated potassium channels (PK,V) that are present in human T cells, inhibits the activation of these cells. ChTX blocks T cell activation induced by signals (e.g., anti-CD2, anti-CD3, ionomycin) that elicit a rise in intracellular calcium ([Ca2+]i) by preventing the elevation of [Ca2+]i in a dose-dependent manner. However, ChTX has no effect on the activation pathways (e.g., anti-CD28, interleukin 2 [IL-2]) that are independent of a rise in [Ca2+]i. In the former case, both proliferative response and lymphokine production (IL-2 and interferon gamma) are inhibited by ChTX. The inhibitory effect of ChTX can be demonstrated when added simultaneously, or up to 4 h after the addition of the stimulants. Since ChTX inhibits both PK,Ca and PK,V, we investigated which channel is responsible for these immunosuppressive effects with the use of two other peptides, noxiustoxin (NxTX) and margatoxin (MgTX), which are specific for PK,V. These studies demonstrate that, similar to ChTX, both NxTX and MgTX inhibit lymphokine production and the rise in [Ca2+]i. Taken together, these data provide evidence that blockade of PK,V affects the Ca(2+)-dependent pathways involved in T lymphocyte proliferation and lymphokine production by diminishing the rise in [Ca2+]i that occurs upon T cell activation.

Effect of the Channel Length on the Transport Characteristics of Transistors Based on Boron-Doped Graphene Ribbons

Directory of Open Access Journals (Sweden)

Paolo Marconcini

2018-04-01

Full Text Available Substitutional boron doping of devices based on graphene ribbons gives rise to a unipolar behavior, a mobility gap, and an increase of the I O N / I O F F ratio of the transistor. Here we study how this effect depends on the length of the doped channel. By means of self-consistent simulations based on a tight-binding description and a non-equilibrium Green’s function approach, we demonstrate a promising increase of the I O N / I O F F ratio with the length of the channel, as a consequence of the different transport regimes in the ON and OFF states. Therefore, the adoption of doped ribbons with longer aspect ratios could represent a significant step toward graphene-based transistors with an improved switching behavior.

Channel Extension in Deep-Water Distributive Systems

Science.gov (United States)

Hoyal, D. C.; Sheets, B. A.

2007-12-01

acceleration to Fr'-critical conditions and the formation of a depositional hydraulic jump, which perturbs sediment transport and ends channel extension. Similar morphodynamic length scale controls are observed in shallow water fan-delta experiments (e.g., SAFL DB-03) and in 2-D depositional cyclic steps. The experiments seem to explain two interesting observations from the earlier self-organized fan experiments and from real submarine fans. Firstly, the observation of 'perched' fills at the steep entrances to salt withdrawal minibasins (e.g., in the Gulf of Mexico) suggesting higher sedimentation rates (or inefficient sediment transport) on higher slopes (initially higher than at the slope break downstream). Secondly, strong progradation as the fan evolves and slope decreases in 'perched' fans suggests increasing flow efficiency on lower slopes, at least over a certain window of parameter space. Apparently deep water systems have a tendency to self-regulate even when flows differ significantly in initial density. The observed modulation to Fr'-critical flow appears to be an important control on length scales in deep- water distributive channel systems, potentially explaining strong deepwater progradation or 'delta-like' patterns that have remained paradoxical. Near critical conditions have been inferred from observations of many active submarine fans but the extent to which these results from conservative density currents apply to non-conservative and potentially 'ignitive' turbidity currents is the subject of ongoing investigation.

Channel Bottom Morphology in the Deltaic Reach of the Song Hau (mekong) River Channel in Vietnam

Science.gov (United States)

Allison, M. A.; Weathers, H. D., III; Meselhe, E. A.

2016-02-01

Boat-based, channel bathymetry and bankline elevation studies were conducted in the tidal and estuarine Mekong River channel using multibeam bathymetry and LIDAR corrected for elevation by RTK satellite positioning. Two mapping campaigns, one at high discharge in October 2014 and one at low discharge in March 2015, were conducted in the lower 100 km reach of the Song Hau distributary channel to (1) examine bottom morphology and its relationship to sediment transport, and (2) to provide information to setup the grid for a multi-dimensional and reduced complexity models of channel hydrodynamics and sediment dynamics. Sand fields were identified in multibeam data by the presence of dunes that were as large as 2-4 m high and 40-80 m wavelength and by clean sands in bottom grabs. Extensive areas of sand at the head and toe of mid-channel islands displayed 10-25 m diameter circular pits that could be correlated with bucket dredge, sand mining activities observed at some of the sites. Large areas of the channel floor were relict (containing little or no modern sediment) in the high discharge campaign, identifiable by the presence of along channel erosional furrows and terraced outcrops along the channel floor and margins. Laterally extensive flat areas were also observed in the channel thalweg. Both these and the relict areas were sampled by bottom grab as stiff silty clays. Complex cross-channel combinations of these morphologies were observed in some transects, suggesting strong bottom steering of tidal and riverine currents. Relative to high discharge, transects above and below the salt penetration limit showed evidence of shallowing in the thalweg and adjacent sloping areas at low discharge in March 2015. This shallowing, combined with the reduced extent of sand fields and furrowed areas, and soft muds in grabs, suggests seasonal trapping of fine grained sediment is occurring by estuarine and tidal circulation.

Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

Science.gov (United States)

Zeng, Wei-Zheng; Liu, Di-Shi; Liu, Lu; She, Liang; Wu, Long-Jun; Xu, Tian-Le

2015-09-15

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.

The effects of drain scatterings on the electron transport properties of strained-Si diodes with ballistic and non-ballistic channels

International Nuclear Information System (INIS)

Yasenjan Ghupur; Mamtimin Geni; Mamatrishat Mamat; Abudukelimu Abudureheman

2015-01-01

The effects of multiple scattering on the electron transport properties in drain regions are numerically investigated for the cases of strained-Si diodes with or without scattering in the channel. The performance of non-ballistic (with scattering) channel Si-diodes is compared with that of ballistic (without scattering) channel Si-diodes, using the strain and scattering model. Our results show that the values of the electron velocity and the current in the strain model are higher than the respective values in the unstrained model, and the values of the velocity and the current in the ballistic channel model are higher than the respective values in the non-ballistic channel model. In the strain and scattering models, the effect of each carrier scattering mechanism on the performance of the Si-diodes is analyzed in the drain region. For the ballistic channel model, our results show that inter-valley optical phonon scattering improves device performance, whereas intra-valley acoustic phonon scattering degrades device performance. For the strain model, our results imply that the larger energy splitting of the strained Si could suppress the inter-valley phonon scattering rate. In conclusion, for the drain region, investigation of the strained-Si and scattering mechanisms are necessary, in order to improve the performance of nanoscale ballistic regime devices. (paper)

A Mathematical Model of Solute Coupled Water Transport in Toad Intestine Incorporating Recirculation of the Actively Transported Solute

DEFF Research Database (Denmark)

Larsen, Erik Hviid; Sørensen, Jakob Balslev; Sørensen, Jens Nørkær

2000-01-01

those of tight junction and interspace basement membrane by convection-diffusion. With solute permeability of paracellular pathway large relative to paracellular water flow, the paracellular flux ratio of the solute (influx/outflux) is small (2-4) in agreement with experiments. The virtual solute......A mathematical model of an absorbing leaky epithelium is developed for analysis of solute coupled water transport. The non-charged driving solute diffuses into cells and is pumped from cells into the lateral intercellular space (lis). All membranes contain water channels with the solute passing...... increases with hydraulic conductance of the pathway carrying water from mucosal solution into lis. Uphill water transport is accomplished, but with high hydraulic conductance of cell membranes strength of transport is obscured by water flow through cells. Anomalous solvent drag occurs when back flux...

Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

International Nuclear Information System (INIS)

Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

1989-01-01

Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release

Magnetic Field and Gravity Effects on Peristaltic Transport of a Jeffrey Fluid in an Asymmetric Channel

Directory of Open Access Journals (Sweden)

A. M. Abd-Alla

2014-01-01

Full Text Available In this paper, the peristaltic flow of a Jeffrey fluid in an asymmetric channel has been investigated. Mathematical modeling is carried out by utilizing long wavelength and low Reynolds number assumptions. Closed form expressions for the pressure gradient, pressure rise, stream function, axial velocity, and shear stress on the channel walls have been computed numerically. Effects of the Hartmann number, the ratio of relaxation to retardation times, time-mean flow, the phase angle and the gravity field on the pressure gradient, pressure rise, streamline, axial velocity, and shear stress are discussed in detail and shown graphically. The results indicate that the effect of Hartmann number, ratio of relaxation to retardation times, time-mean flow, phase angle, and gravity field are very pronounced in the peristaltic transport phenomena. Comparison was made with the results obtained in the presence and absence of magnetic field and gravity field.

Collaboration between physical activity researchers and transport planners

DEFF Research Database (Denmark)

Crist, Katie; Bolling, Khalisa; Schipperijn, Jasper

2018-01-01

Collaboration between physical activity (PA) researchers and transport planners is a recommended strategy to combat the physical inactivity epidemic. Data collected by PA researchers could be used to identify, implement and evaluate active transport (AT) projects. However, despite aligned interests......, researchers and transport planners rarely collaborate. This study utilized qualitative methods to 1) gain an in-depth understanding of the data utilized in AT planning, 2) explore the utility of Global Positioning Systems (GPS) and accelerometer data in supporting the planning process, 3) identify...... expertise in health or transport planning. A thematic analysis was conducted following structural coding by two researchers. The analysis revealed that geographic and physical activity data that are current, local, objective and specific to individual AT trips would improve upon currently available data...

Interaction between Ca++-channel antagonists and α2-adrenergic receptors in rabbit ileal cell membrane

International Nuclear Information System (INIS)

Homeidan, F.R.; Wicks, J.; Cusolito, S.; El-Sabban, M.E.; Sharp, G.W.G.; Donowitz, M.

1986-01-01

An interaction between Ca ++ -channel antagonists and the α 2 -adrenergic receptor on active electrolyte transport was demonstrated in rabbit ileum. Clonidine, an α 2 -agonist, stimulated NaCl absorption apparently by Ca ++ -channel antagonism since it inhibited 45 Ca ++ uptake across the basolateral membrane and decreased total ileal calcium content. This stimulation was inhibited by the Ca ++ -channel antagonists dl- and l-verapamil and cadmium but not by nifedipine. The binding of 3 H-yohimbine, a specific α 2 -adrenergic antagonist, was studied on purified ileal cell membranes using a rapid filtration technique. dl-Verapamil and Cd ++ inhibited the specific binding of 3 H-yohimbine over the same concentration range in which they affected transport. In contrast, nifedipine had no effect on binding, just as it had no effect on clonidine-stimulated NaCl absorption. These data demonstrate that there is an interaction between Ca ++ -channels and α 2 -adrenergic receptors in ileal basolateral membranes. Some Ca ++ -channel antagonists alter α 2 -adrenergic binding to the receptor and α 2 -agonist binding leads to changes in Ca ++ entry. A close spatial relationship between the Ca ++ -channel and the α 2 -receptor could explain the data

Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons.

Science.gov (United States)

Lazcano-Pérez, Fernando; Castro, Héctor; Arenas, Isabel; García, David E; González-Muñoz, Ricardo; Arreguín-Espinosa, Roberto

2016-05-05

The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P. caribaeorum venom on voltage-gated sodium channel (NaV1.7), voltage-gated calcium channel (CaV2.2), the A-type transient outward (IA) and delayed rectifier (IDR) currents of KV channels of the superior cervical ganglion (SCG) neurons of the rat. These results showed that the venom reversibly delays the inactivation process of voltage-gated sodium channels and inhibits voltage-gated calcium and potassium channels in this mammalian model. The compounds responsible for these effects seem to be low molecular weight peptides. Together, these results provide evidence for the potential use of zoanthids as a novel source of cnidarian toxins active on voltage-gated ion channels.

Modelling activity transport behavior in PWR plant

International Nuclear Information System (INIS)

Henshaw, Jim; McGurk, John; Dickinson, Shirley; Burrows, Robert; Hinds, Kelvin; Hussey, Dennis; Deshon, Jeff; Barrios Figueras, Joan Pau; Maldonado Sanchez, Santiago; Fernandez Lillo, Enrique; Garbett, Keith

2012-09-01

The activation and transport of corrosion products around a PWR circuit is a major concern to PWR plant operators as these may give rise to high personnel doses. The understanding of what controls dose rates on ex-core surfaces and shutdown releases has improved over the years but still several questions remain unanswered. For example the relative importance of particle and soluble deposition in the core to activity levels in the plant is not clear. Wide plant to plant and cycle to cycle variations are noted with no apparent explanations why such variations are observed. Over the past few years this group have been developing models to simulate corrosion product transport around a PWR circuit. These models form the basis for the latest version of the BOA code and simulate the movement of Fe and Ni around the primary circuit. Part of this development is to include the activation and subsequent transport of radioactive species around the circuit and this paper describes some initial modelling work in this area. A simple model of activation, release and deposition is described and then applied to explain the plant behaviour at Sizewell B and Vandellos II. This model accounts for activation in the core, soluble and particulate activity movement around the circuit and for activity capture ex-core on both the inner and outer oxides. The model gives a reasonable comparison with plant observations and highlights what controls activity transport in these plants and importantly what factors can be ignored. (authors)

Physiology and pathophysiology of ClC-K/barttin channels.

Science.gov (United States)

Fahlke, Christoph; Fischer, Martin

2010-01-01

ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology, and pathophysiology of ClC-K/barttin channels.

Physiology and pathophysiology of ClC-K/barttin channels

Directory of Open Access Journals (Sweden)

Christoph eFahlke

2010-11-01

Full Text Available ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology and pathophysiology of ClC-K/barttin channels.

Proton channels and exchangers in cancer.

Science.gov (United States)

Spugnini, Enrico Pierluigi; Sonveaux, Pierre; Stock, Christian; Perez-Sayans, Mario; De Milito, Angelo; Avnet, Sofia; Garcìa, Abel Garcìa; Harguindey, Salvador; Fais, Stefano

2015-10-01

Although cancer is characterized by an intratumoral genetic heterogeneity, a totally deranged pH control is a common feature of most cancer histotypes. Major determinants of aberrant pH gradient in cancer are proton exchangers and transporters, including V-ATPase, Na+/H+ exchanger (NHE), monocarboxylate transporters (MCTs) and carbonic anhydrases (CAs). Thanks to the activity of these proton transporters and exchangers, cancer becomes isolated and/or protected not only from the body reaction against the growing tumor, but also from the vast majority of drugs that when protonated into the acidic tumor microenvironment do not enter into cancer cells. Proton transporters and exchangers represent a key feature tumor cells use to survive in the very hostile microenvironmental conditions that they create and maintain. Detoxifying mechanisms may thus represent both a key survival option and a selection outcome for cells that behave as unicellular microorganisms rather than belonging to an organ, compartment or body. It is, in fact, typical of malignant tumors that, after a clinically measurable yet transient initial response to a therapy, resistant tumor clones emerge and proliferate, thus bursting a more malignant behavior and rapid tumor progression. This review critically presents the background of a novel and efficient approach that aims to fight cancer through blocking or inhibiting well characterized proton exchangers and transporters active in human cancer cells. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. Copyright © 2014 Elsevier B.V. All rights reserved.

ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels.

Science.gov (United States)

Bryant, Sheenah L; Eixenberger, Josh E; Rossland, Steven; Apsley, Holly; Hoffmann, Connor; Shrestha, Nisha; McHugh, Michael; Punnoose, Alex; Fologea, Daniel

2017-12-16

The insufficient understanding of unintended biological impacts from nanomaterials (NMs) represents a serious impediment to their use for scientific, technological, and medical applications. While previous studies have focused on understanding nanotoxicity effects mostly resulting from cellular internalization, recent work indicates that NMs may interfere with transmembrane transport mechanisms, hence enabling contributions to nanotoxicity by affecting key biological activities dependent on transmembrane transport. In this line of inquiry, we investigated the effects of charged nanoparticles (NPs) on the transport properties of lysenin, a pore-forming toxin that shares fundamental features with ion channels such as regulation and high transport rate. The macroscopic conductance of lysenin channels greatly diminished in the presence of cationic ZnO NPs. The inhibitory effects were asymmetrical relative to the direction of the electric field and addition site, suggesting electrostatic interactions between ZnO NPs and a binding site. Similar changes in the macroscopic conductance were observed when lysenin channels were reconstituted in neutral lipid membranes, implicating protein-NP interactions as the major contributor to the reduced transport capabilities. In contrast, no inhibitory effects were observed in the presence of anionic SnO 2 NPs. Additionally, we demonstrate that inhibition of ion transport is not due to the dissolution of ZnO NPs and subsequent interactions of zinc ions with lysenin channels. We conclude that electrostatic interactions between positively charged ZnO NPs and negative charges within the lysenin channels are responsible for the inhibitory effects on the transport of ions. These interactions point to a potential mechanism of cytotoxicity, which may not require NP internalization.

Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor.

Science.gov (United States)

Hinson, Shannon R; Clift, Ian C; Luo, Ningling; Kryzer, Thomas J; Lennon, Vanda A

2017-05-23

Aquaporin-4 (AQP4) water channel-specific IgG distinguishes neuromyelitis optica (NMO) from multiple sclerosis and causes characteristic immunopathology in which central nervous system (CNS) demyelination is secondary. Early events initiating the pathophysiological outcomes of IgG binding to astrocytic AQP4 are poorly understood. CNS lesions reflect events documented in vitro following IgG interaction with AQP4: AQP4 internalization, attenuated glutamate uptake, intramyelinic edema, interleukin-6 release, complement activation, inflammatory cell recruitment, and demyelination. Here, we demonstrate that AQP4 internalization requires AQP4-bound IgG to engage an astrocytic Fcγ receptor (FcγR). IgG-lacking Fc redistributes AQP4 within the plasma membrane and induces interleukin-6 release. However, AQP4 endocytosis requires an activating FcγR's gamma subunit and involves astrocytic membrane loss of an inhibitory FcγR, CD32B. Interaction of the IgG-AQP4 complex with FcγRs triggers coendocytosis of the excitatory amino acid transporter 2 (EAAT2). Requirement of FcγR engagement for internalization of two astrocytic membrane proteins critical to CNS homeostasis identifies a complement-independent, upstream target for potential early therapeutic intervention in NMO.

Dynamics of polynucleotide transport through nanometre-scale pores

CERN Document Server

Meller, A

2003-01-01

The transport of biopolymers through large membrane channels is a ubiquitous process in biology. It is central to processes such as gene transfer by transduction and RNA transport through nuclear pore complexes. The transport of polymers through nanoscopic channels is also of interest to physicists and chemists studying the effects of steric, hydrodynamic, and electrostatic interactions between polymers and confining walls. Single-channel ion current measurements have been recently used to study the transport of biopolymers, and in particular single-stranded DNA and RNA molecules, through nanometre-size channels. Under the influence of an electric field, the negatively charged polynucleotides can be captured and drawn through the channel in a process termed 'translocation'. During translocation, the ion current flowing through the channel is mostly blocked, indicating the presence of the polymer inside the channel. The current blockades were found to be sensitive to the properties of the biopolymers such as t...

Taurine activates delayed rectifier KV channels via a metabotropic pathway in retinal neurons

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Bulley, Simon; Liu, Yufei; Ripps, Harris; Shen, Wen

2013-01-01

Taurine is one of the most abundant amino acids in the retina, throughout the CNS, and in heart and muscle cells. In keeping with its broad tissue distribution, taurine serves as a modulator of numerous basic processes, such as enzyme activity, cell development, myocardial function and cytoprotection. Despite this multitude of functional roles, the precise mechanism underlying taurine's actions has not yet been identified. In this study we report findings that indicate a novel role for taurine in the regulation of voltage-gated delayed rectifier potassium (KV) channels in retinal neurons by means of a metabotropic receptor pathway. The metabotropic taurine response was insensitive to the Cl− channel blockers, picrotoxin and strychnine, but it was inhibited by a specific serotonin 5-HT2A receptor antagonist, MDL11939. Moreover, we found that taurine enhanced KV channels via intracellular protein kinase C-mediated pathways. When 5-HT2A receptors were expressed in human embryonic kidney cells, taurine and AL34662, a non-specific 5-HT2 receptor activator, produced a similar regulation of KIR channels. In sum, this study provides new evidence that taurine activates a serotonin system, apparently via 5-HT2A receptors and related intracellular pathways. PMID:23045337

Assessment of Physical Activity and Active Transport Among School ...

International Development Research Centre (IDRC) Digital Library (Canada)

Assessment of Physical Activity and Active Transport Among School Children in Kenya, Nigeria, and Mozambique ... International Water Resources Association, in close collaboration with IDRC, is holding a webinar titled “Climate change and adaptive water management: Innovative solutions from the Global South”.

The role of volume-sensitive ion transport systems in regulation of epithelial transport

DEFF Research Database (Denmark)

Hoffmann, Else Kay; Schettino, T; Marshall, W S

2007-01-01

This review focuses on using the knowledge on volume-sensitive transport systems in Ehrlich ascites tumour cells and NIH-3T3 cells to elucidate osmotic regulation of salt transport in epithelia. Using the intestine of the European eel (Anguilla anguilla) (an absorptive epithelium of the type...... on the apical side and the Na+/K+ ATPase, NKCC1 and a K+ channel on the basolateral side. Osmotic control of Cl- secretion across the operculum epithelium includes: (i) hyperosmotic shrinkage activation of NKCC1 via PKC, MLCK, p38, OSR1 and SPAK; (ii) deactivation of NKCC by hypotonic cell swelling...

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels

OpenAIRE

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl− channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl− channel activity of wild-type CFTR and delF508-CFTR mutant.The effects of n-alkanols like octanol on CFTR activity were measured by iodide (125I) efflux and patch-clamp techniques o...

Blockade of TRPM7 channel activity and cell death by inhibitors of 5-lipoxygenase.

Directory of Open Access Journals (Sweden)

Hsiang-Chin Chen

2010-06-01

Full Text Available TRPM7 is a ubiquitous divalent-selective ion channel with its own kinase domain. Recent studies have shown that suppression of TRPM7 protein expression by RNA interference increases resistance to ischemia-induced neuronal cell death in vivo and in vitro, making the channel a potentially attractive pharmacological target for molecular intervention. Here, we report the identification of the 5-lipoxygenase inhibitors, NDGA, AA861, and MK886, as potent blockers of the TRPM7 channel. Using a cell-based assay, application of these compounds prevented cell rounding caused by overexpression of TRPM7 in HEK-293 cells, whereas inhibitors of 12-lipoxygenase and 15-lipoxygenase did not prevent the change in cell morphology. Application of the 5-lipoxygenase inhibitors blocked heterologously expressed TRPM7 whole-cell currents without affecting the protein's expression level or its cell surface concentration. All three inhibitors were also effective in blocking the native TRPM7 current in HEK-293 cells. However, two other 5-lipoxygenase specific inhibitors, 5,6-dehydro-arachidonic acid and zileuton, were ineffective in suppressing TRPM7 channel activity. Targeted knockdown of 5-lipoxygenase did not reduce TRPM7 whole-cell currents. In addition, application of 5-hydroperoxyeicosatetraenoic acid (5-HPETE, the product of 5-lipoxygenase, or 5-HPETE's downstream metabolites, leukotriene B4 and leukotriene D4, did not stimulate TRPM7 channel activity. These data suggested that NDGA, AA861, and MK886 reduced the TRPM7 channel activity independent of their effect on 5-lipoxygenase activity. Application of AA861 and NDGA reduced cell death for cells overexpressing TRPM7 cultured in low extracellular divalent cations. Moreover, treatment of HEK-293 cells with AA861 increased cell resistance to apoptotic stimuli to a level similar to that obtained for cells in which TRPM7 was knocked down by RNA interference. In conclusion, NDGA, AA861, and MK886 are potent blockers of

Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons

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Fernando Lazcano-Pérez

2016-05-01

Full Text Available The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P. caribaeorum venom on voltage-gated sodium channel (NaV1.7, voltage-gated calcium channel (CaV2.2, the A-type transient outward (IA and delayed rectifier (IDR currents of KV channels of the superior cervical ganglion (SCG neurons of the rat. These results showed that the venom reversibly delays the inactivation process of voltage-gated sodium channels and inhibits voltage-gated calcium and potassium channels in this mammalian model. The compounds responsible for these effects seem to be low molecular weight peptides. Together, these results provide evidence for the potential use of zoanthids as a novel source of cnidarian toxins active on voltage-gated ion channels.

The molecular mechanism of multi-ion conduction in K{sup +} channels

Energy Technology Data Exchange (ETDEWEB)

Gwan, J.F.

2007-01-19

Steered molecular dynamics (SMD) simulation method is applied to a fully solvated membrane-channel model for studying the ion permeation process in potassium channels. The channel model is based on the crystallographic structure of a prokaryotic K{sup +} channel- the KcsA channel, which is a representative of most known eukaryotic K{sup +} channels. It has long been proposed that the ion transportation in a conventional K{sup +}-channel follows a multi-ion fashion: permeating ions line in a queue in the channel pore and move in a single file through the channel. The conventional view of multi-ion transportation is that the electrostatic repulsion between ions helps to overcome the attraction between ions and the channel pore. In this study, we proposed two SMD simulation schemes, referred to 'the single-ion SMD' simulations and 'the multi-ion SMD' simulations. Concerted movements of a K-W-K sequence in the selectivity filter were observed in the single-ion SMD simulations. The analysis of the concerted movement reveals the molecular mechanism of the multi-ion transportation. It shows that, rather than the long range electrostatic interaction, the short range polar interaction is a more dominant factor in the multi-ion transportation. The polar groups which play a role in the concerted transportation are the water molecules and the backbone carbonyl groups of the selectivity filter. The polar interaction is sensitive to the relative orientation of the polar groups. By changing the orientation of a polar group, the interaction may switch from attractive to repulsive or vice versa. By this means, the energy barrier between binding sites in the selectivity filter can be switched on and off, and therefore the K{sup +} may be able to move to the neighboring binding site without an external driving force. The concerted transportation in the selectivity filter requires a delicate cooperation between K{sup +}, waters, and the backbone carbonyl groups. To

Slick (Kcnt2 Sodium-Activated Potassium Channels Limit Peptidergic Nociceptor Excitability and Hyperalgesia

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Danielle L Tomasello

2017-09-01

Full Text Available The Slick (Kcnt2 sodium-activated potassium (K Na channel is a rapidly gating and weakly voltage-dependent and sodium-dependent potassium channel with no clearly defined physiological function. Within the dorsal root ganglia (DRGs, we show Slick channels are exclusively expressed in small-sized and medium-sized calcitonin gene–related peptide (CGRP-containing DRG neurons, and a pool of channels are localized to large dense-core vesicles (LDCV-containing CGRP. We stimulated DRG neurons for CGRP release and found Slick channels contained within CGRP-positive LDCV translocated to the neuronal membrane. Behavioral studies in Slick knockout (KO mice indicated increased basal heat detection and exacerbated thermal hyperalgesia compared with wild-type littermate controls during neuropathic and chronic inflammatory pain. Electrophysiologic recordings of DRG neurons from Slick KO mice revealed that Slick channels contribute to outward current, propensity to fire action potentials (APs, and to AP properties. Our data suggest that Slick channels restrain the excitability of CGRP-containing neurons, diminishing pain behavior after inflammation and injury.

The TRPM6 Kinase Domain Determines the Mg·ATP Sensitivity of TRPM7/M6 Heteromeric Ion Channels*

Science.gov (United States)

Zhang, Zheng; Yu, Haijie; Huang, Junhao; Faouzi, Malika; Schmitz, Carsten; Penner, Reinhold; Fleig, Andrea

2014-01-01

The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg2+) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with TRPM7. We show that homomeric TRPM6 is highly sensitive to intracellular free Mg2+ and therefore unlikely to be active at physiological levels of [Mg2+]i. Co-expression of TRPM7 and TRPM6 produces heteromeric TRPM7/M6 channels with altered pharmacology and sensitivity to intracellular Mg·ATP compared with homomeric TRPM7. Strikingly, the activity of heteromeric TRPM7/M6 channels is independent of intracellular Mg·ATP concentrations, essentially uncoupling channel activity from cellular energy status. Disruption of TRPM6 kinase phosphorylation activity re-introduces Mg·ATP sensitivity to the heteromeric channel similar to that of TRPM7. Thus, TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7·M6 channel complex. PMID:24385424

The TRPM6 kinase domain determines the Mg·ATP sensitivity of TRPM7/M6 heteromeric ion channels.

Science.gov (United States)

Zhang, Zheng; Yu, Haijie; Huang, Junhao; Faouzi, Malika; Schmitz, Carsten; Penner, Reinhold; Fleig, Andrea

2014-02-21

The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg(2+)) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with TRPM7. We show that homomeric TRPM6 is highly sensitive to intracellular free Mg(2+) and therefore unlikely to be active at physiological levels of [Mg(2+)]i. Co-expression of TRPM7 and TRPM6 produces heteromeric TRPM7/M6 channels with altered pharmacology and sensitivity to intracellular Mg·ATP compared with homomeric TRPM7. Strikingly, the activity of heteromeric TRPM7/M6 channels is independent of intracellular Mg·ATP concentrations, essentially uncoupling channel activity from cellular energy status. Disruption of TRPM6 kinase phosphorylation activity re-introduces Mg·ATP sensitivity to the heteromeric channel similar to that of TRPM7. Thus, TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7·M6 channel complex.

Alkali pH directly activates ATP-sensitive K+ channels and inhibits insulin secretion in beta-cells.