Effect of pinacidil on norepinephrine- and potassium-induced contractions and membrane potential in rat and human resistance vessels and in rat aorta

International Nuclear Information System (INIS)

Videbaek, L.M.; Aalkjaer, C.; Mulvany, M.J.

1988-01-01

The effect of pinacidil on contractile responses to norepinephrine, potassium, and membrane potential was examined in rat and human resistance vessels. In some experiments rat aorta was also used. Pinacidil (0.1-30 microM) caused a concentration-dependent relaxation of norepinephrine-induced contractions in all vessels studied. In the same concentration range, pinacidil had only little effect on potassium (125 mM) activated rat mesenteric and femoral resistance vessels. In denervated rat mesenteric resistance vessels, a depolarization with potassium (125 mM) before superimposing a norepinephrine tone markedly diminished the effect of pinacidil. In resting rat mesenteric resistance vessels, pinacidil (1-10 microM) caused a hyperpolarization of 10-15 mV. In rat aorta, pinacidil (10 microM) caused a significant (p less than 0.001) increase in 86 Rb+ efflux rate constant whereas 1 microM had no effect. The results of these experiments indicate that the vasodilating effect may be caused by a hyperpolarization of the vascular smooth muscle cell membrane

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.

Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.

Science.gov (United States)

Krenz, Wulf-Dieter C; Rodgers, Edmund W; Baro, Deborah J

2015-01-01

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.

Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.

Directory of Open Access Journals (Sweden)

Wulf-Dieter C Krenz

Full Text Available Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA at type 1 DA receptors (D1Rs are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h. In the presence but not absence of 5nM DA, I h maximal conductance (G max was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP, which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation. Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone.

Science.gov (United States)

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J; Lesport, Pierre; Bourinet, Emmanuel; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-07-18

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans , is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT₂R, with this action being not affected by known ligands of AT₂R. This result points towards novel AT₂R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics.

Oleate induces KATP channel-dependent hyperpolarization in mouse hypothalamic glucose-excited neurons without altering cellular energy charge.

Science.gov (United States)

Dadak, Selma; Beall, Craig; Vlachaki Walker, Julia M; Soutar, Marc P M; McCrimmon, Rory J; Ashford, Michael L J

2017-03-27

The unsaturated fatty acid, oleate exhibits anorexigenic properties reducing food intake and hepatic glucose output. However, its mechanism of action in the hypothalamus has not been fully determined. This study investigated the effects of oleate and glucose on GT1-7 mouse hypothalamic cells (a model of glucose-excited (GE) neurons) and mouse arcuate nucleus (ARC) neurons. Whole-cell and perforated patch-clamp recordings, immunoblotting and cell energy status measures were used to investigate oleate- and glucose-sensing properties of mouse hypothalamic neurons. Oleate or lowered glucose concentration caused hyperpolarization and inhibition of firing of GT1-7 cells by the activation of ATP-sensitive K + channels (K ATP ). This effect of oleate was not dependent on fatty acid oxidation or raised AMP-activated protein kinase activity or prevented by the presence of the UCP2 inhibitor genipin. Oleate did not alter intracellular calcium, indicating that CD36/fatty acid translocase may not play a role. However, oleate activation of K ATP may require ATP metabolism. The short-chain fatty acid octanoate was unable to replicate the actions of oleate on GT1-7 cells. Although oleate decreased GT1-7 cell mitochondrial membrane potential there was no change in total cellular ATP or ATP/ADP ratios. Perforated patch and whole-cell recordings from mouse hypothalamic slices demonstrated that oleate hyperpolarized a subpopulation of ARC GE neurons by K ATP activation. Additionally, in a separate small population of ARC neurons, oleate application or lowered glucose concentration caused membrane depolarization. In conclusion, oleate induces K ATP- dependent hyperpolarization and inhibition of firing of a subgroup of GE hypothalamic neurons without altering cellular energy charge. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance Ca(2+) -activated K(+) channels.

Science.gov (United States)

Xu, Y C; Leung, S W S; Leung, G P H; Man, R Y K

2015-06-01

Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs). At a concentration without direct effect on vascular tone, kaempferol (3 × 10(-6) M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin-induced relaxation was not affected by N(ω)-nitro-L-arginine methyl ester, an inhibitor of NO synthase (10(-4) M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10(-6) M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10(-3) M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel (KCa 1.1; 10(-7) M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin. The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa 1.1 channels. © 2015 The British Pharmacological Society.

Inward rectifier potassium (Kir2.1) channels as end‐stage boosters of endothelium‐dependent vasodilators

Science.gov (United States)

Dalsgaard, Thomas; Bonev, Adrian D.; Nelson, Mark T.

2016-01-01

Key points Increase in endothelial cell (EC) calcium activates calcium‐sensitive intermediate and small conductance potassium (IK and SK) channels, thereby causing hyperpolarization and endothelium‐dependent vasodilatation.Endothelial cells express inward rectifier potassium (Kir) channels, but their role in endothelium‐dependent vasodilatation is not clear.In the mesenteric arteries, only ECs, but not smooth muscle cells, displayed Kir currents that were predominantly mediated by the Kir2.1 isoform.Endothelium‐dependent vasodilatations in response to muscarinic receptor, TRPV4 (transient receptor potential vanilloid 4) channel and IK/SK channel agonists were highly attenuated by Kir channel inhibitors and by Kir2.1 channel knockdown.These results point to EC Kir channels as amplifiers of vasodilatation in response to increases in EC calcium and IK/SK channel activation and suggest that EC Kir channels could be targeted to treat endothelial dysfunction, which is a hallmark of vascular disorders. Abstract Endothelium‐dependent vasodilators, such as acetylcholine, increase intracellular Ca2+ through activation of transient receptor potential vanilloid 4 (TRPV4) channels in the plasma membrane and inositol trisphosphate receptors in the endoplasmic reticulum, leading to stimulation of Ca2+‐sensitive intermediate and small conductance K+ (IK and SK, respectively) channels. Although strong inward rectifier K+ (Kir) channels have been reported in the native endothelial cells (ECs) their role in EC‐dependent vasodilatation is not clear. Here, we test the idea that Kir channels boost the EC‐dependent vasodilatation of resistance‐sized arteries. We show that ECs, but not smooth muscle cells, of small mesenteric arteries have Kir currents, which are substantially reduced in EC‐specific Kir2.1 knockdown (EC‐Kir2.1 −/−) mice. Elevation of extracellular K+ to 14 mm caused vasodilatation of pressurized arteries, which was prevented by endothelial

Cell-Type Specific Development of the Hyperpolarization-Activated Current, Ih, in Prefrontal Cortical Neurons

Directory of Open Access Journals (Sweden)

Sha-Sha Yang

2018-05-01

Full Text Available H-current, also known as hyperpolarization-activated current (Ih, is an inward current generated by the hyperpolarization-activated cyclic nucleotide-gated (HCN cation channels. Ih plays an essential role in regulating neuronal properties, synaptic integration and plasticity, and synchronous activity in the brain. As these biological factors change across development, the brain undergoes varying levels of vulnerability to disorders like schizophrenia that disrupt prefrontal cortex (PFC-dependent function. However, developmental changes in Ih in PFC neurons remains untested. Here, we examine Ih in pyramidal neurons vs. gamma-aminobutyric acid (GABAergic parvalbumin-expressing (PV+ interneurons in developing mouse PFC. Our findings show that the amplitudes of Ih in these cell types are identical during the juvenile period but differ at later time points. In pyramidal neurons, Ih amplitude significantly increases from juvenile to adolescence and follows a similar trend into adulthood. In contrast, the amplitude of Ih in PV+ interneurons decreases from juvenile to adolescence, and does not change from adolescence to adulthood. Moreover, the kinetics of HCN channels in pyramidal neurons is significantly slower than in PV+ interneurons, with a gradual decrease in pyramidal neurons and a gradual increase in PV+ cells across development. Our study reveals distinct developmental trajectories of Ih in pyramidal neurons and PV+ interneurons. The cell-type specific alteration of Ih during the critical period from juvenile to adolescence reflects the contribution of Ih to the maturation of the PFC and PFC-dependent function. These findings are essential for a better understanding of normal PFC function, and for elucidating Ih’s crucial role in the pathophysiology of neurodevelopmental disorders.

Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance a2+-activated K+ channels

Science.gov (United States)

Xu, Y C; Leung, S W S; Leung, G P H; Man, R Y K

2015-01-01

Background and Purpose Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. Experimental Approach The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs). Key Results At a concentration without direct effect on vascular tone, kaempferol (3 × 10−6 M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin-induced relaxation was not affected by Nω-nitro-L-arginine methyl ester, an inhibitor of NO synthase (10−4 M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10−6 M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10−3 M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel (KCa1.1; 10−7 M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin. Conclusions and Implications The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa1.1 channels. PMID:25652142

Diadenosine pentaphosphate affects electrical activity in guinea pig atrium via activation of potassium acetylcholine-dependent inward rectifier.

Science.gov (United States)

Abramochkin, Denis V; Karimova, Viktoria M; Filatova, Tatiana S; Kamkin, Andre

2017-07-01

Diadenosine pentaphosphate (Ap5A) belongs to the family of diadenosine polyphosphates, endogenously produced compounds that affect vascular tone and cardiac performance when released from platelets. The previous findings indicate that Ap5A shortens action potentials (APs) in rat myocardium via activation of purine P2 receptors. The present study demonstrates alternative mechanism of Ap5A electrophysiological effects found in guinea pig myocardium. Ap5A (10 -4  M) shortens APs in guinea pig working atrial myocardium and slows down pacemaker activity in the sinoatrial node. P1 receptors antagonist DPCPX (10 -7  M) or selective GIRK channels blocker tertiapin (10 -6  M) completely abolished all Ap5A effects, while P2 blocker PPADS (10 -4  M) was ineffective. Patch-clamp experiments revealed potassium inward rectifier current activated by Ap5A in guinea pig atrial myocytes. The current was abolished by DPCPX or tertiapin and therefore was considered as potassium acetylcholine-dependent inward rectifier (I KACh ). Thus, unlike rat, in guinea pig atrium Ap5A produces activation of P1 receptors and subsequent opening of KACh channels leading to negative effects on cardiac electrical activity.

Hyperpolarized 1-13C Pyruvate Imaging of Porcine Cardiac Metabolism shift by GIK Intervention

DEFF Research Database (Denmark)

Søvsø Szocska Hansen, Esben; Tougaard, Rasmus Stilling; Mikkelsen, Emmeli

to evaluate the general feasibility to detect an imposed shift in metabolic substrate utilization during metabolic modulation with glucose, insulin and potassium (GIK) infusion. This study demonstrates that hyperpolarized 13C-pyruvate, in a large animal, is a feasible method for cardiac studies, and...

X-radiation effect on the hyperpolarization of cells, the adeninenucleotide content and the distribution of sodium and potassium ions

Energy Technology Data Exchange (ETDEWEB)

Frol' kis, V V [Akademiya Meditsinskikh Nauk Ukrainskoj SSR, Kiev. Inst. Gerontologii

1975-03-01

X-radiation prevents the progress of hyperpolarization of muscle and liver cells caused by hormones (estradioldipropyonate, deoxycorticosteron-acetate and insulin) and by the loss of blood. X-radiation offsets the redistribution of K/sup +/ and Na/sup +/ ions caused by hyperpolarization and does not change the level of ATP, ADP, CP and Pi. X-radiation is suggested to affect the hyperpolarization and the ionic shifts via the system of protein biosynthesis.

Transportable hyperpolarized metabolites

Science.gov (United States)

Ji, Xiao; Bornet, Aurélien; Vuichoud, Basile; Milani, Jonas; Gajan, David; Rossini, Aaron J.; Emsley, Lyndon; Bodenhausen, Geoffrey; Jannin, Sami

2017-01-01

Nuclear spin hyperpolarization of 13C-labelled metabolites by dissolution dynamic nuclear polarization can enhance the NMR signals of metabolites by several orders of magnitude, which has enabled in vivo metabolic imaging by MRI. However, because of the short lifetime of the hyperpolarized magnetization (typically <1 min), the polarization process must be carried out close to the point of use. Here we introduce a concept that markedly extends hyperpolarization lifetimes and enables the transportation of hyperpolarized metabolites. The hyperpolarized sample can thus be removed from the polarizer and stored or transported for use at remote MRI or NMR sites. We show that hyperpolarization in alanine and glycine survives 16 h storage and transport, maintaining overall polarization enhancements of up to three orders of magnitude. PMID:28072398

MR imaging of the stomach and relaxation measurement with intraluminal hyperpolarized 129Xenon gas

International Nuclear Information System (INIS)

Yanagawa, Yasuhiro; Kimura, Atsuomi; Fujiwara, Hideaki; Kinoshita, Yoshimasa; Hattori, Mineyuki; Hiraga, Takashi; Iida, Hidehiro

2001-01-01

Using laser optical pumping, the nuclear spin polarization of noble gases can be strongly enhanced. The purpose of this study was to make a simple apparatus that can provide hyperpolarized 129 Xe gas, which can then be used in an attempt to obtain magnetic resonance imaging (MRI). We would also like to study the relaxation behavior of hyperpolarized 129 Xe gas through the measurement of the relaxation time. First, we demonstrated that hyperpolarized 129 Xe gas can be applied to magnetic resonance imaging of the stomach, by using a rat as a model. This was performed under a 4.7 T magnet field using the following imaging parameters for the hyperpolarized 129 Xe gas: TR=50 ms, TE=15 ms, FOV=10 x 10 cm 2 , matrix size 64 x 64, THK=2.54 cm. By using these parameters, we were able to obtain a hyperpolarized image of the stomach in rats for the first time. Next, we measured the relaxation times of the hyperpolarized 129 Xe gas enclosed in cavities such as the stomach of rats as well as in phantoms created by glass and gelatin bulbs. The cavity size dependency of the relaxation time was analyzed on the basis of the kinetic theory of gases. This analysis showed a linear relationship between the relaxation rate (1/T 1 ) and a square inverse of the cavity diameter (1/d 2 ). From this relationship, the wall effect on the 129 Xe relaxation can be estimated in the novel parameter t 1 , wall . This shows drastic dependency on the material of the wall, suggesting a potential use of the relaxation experiment as a diagnostic tool for organ surfaces in the future. (author)

Hyperpolarized 129Xe as an NMR probe for functional studies

International Nuclear Information System (INIS)

Wolber, J.

2000-01-01

The nuclear spin polarization of 129 Xe can be enhanced by several orders of magnitude using optical pumping techniques, resulting in a dramatic enhancement of the 129 Xe Nuclear Magnetic Resonance (NMR) signal. The 'hyperpolarized' gas can be used for Magnetic Resonance Imaging (MRI) of the void spaces of the lungs after introduction of the gas into the respiratory system. Furthermore, the high solubility of xenon in blood and lipids suggests the use of 129 Xe NMR for studying blood flow, permeability, perfusion and blood volume. Hyperpolarized 129 Xe MRI has the potential of combining the high sensitivity and functional information of radioactive tracer studies with the high spatial and temporal resolution of MRI. The spin-lattice relaxation time T 1 of 129 Xe in blood determines the loss of polarization during transit from the lungs to the tissue of interest. A difference in the relaxation times of xenon in oxygenated and deoxygenated blood could be used as a contrast mechanism in functional Magnetic Resonance Imaging (fMRI). In this thesis, the hyperpolarized 129 Xe T 1 in human blood is measured in vitro as a function of blood oxygenation, and the relevant relaxation mechanisms are discussed. A new and unexpected finding is that the hyperpolarized 129 Xe NMR spectrum in blood is highly sensitive to blood oxygenation. Therefore, hyperpolarized 129 Xe NMR provides a powerful means of measuring blood oxygenation quantitatively and non-invasively. The interaction of xenon with hemoglobin is responsible for an oxygen-dependent shift of the 129 Xe NMR resonance of xenon in red blood cells. Injection delivery of hyperpolarized 129 Xe in solution could be a more efficient method of administrating the gas for functional NMR studies. For this purpose, suitable biocompatible carrier media have been studied. In particular, the use of perfluorocarbon emulsions, which are already in use as blood substitutes, as delivery media for hyperpolarized 129 Xe has been investigates

Persistent discharges in dentate gyrus perisoma-inhibiting interneurons require hyperpolarization-activated cyclic nucleotide-gated channel activation.

Science.gov (United States)

Elgueta, Claudio; Köhler, Johannes; Bartos, Marlene

2015-03-11

Parvalbumin (PV)-expressing perisoma-inhibiting interneurons (PIIs) of the dentate gyrus integrate rapidly correlated synaptic inputs and generate short-duration action potentials that propagate along the axon to their output synapses, supporting fast inhibitory signaling onto their target cells. Here we show that PV-PIIs in rat and mouse dentate gyrus (DG) integrate their intrinsic activity over time and can turn into a persistent firing mode characterized by the ability to generate long-lasting trains of action potentials at ∼50 Hz in the absence of additional inputs. Persistent firing emerges in the axons remote from the axon initial segment and markedly depends on hyperpolarization-activated cyclic nucleotide-gated channel (HCNC) activation. Persistent firing properties are modulated by intracellular Ca(2+) levels and somatic membrane potential. Detailed computational single-cell PIIs models reveal that HCNC-mediated conductances can contribute to persistent firing during conditions of a shift in their voltage activation curve to more depolarized potentials. Paired recordings from PIIs and their target granule cells show that persistent firing supports strong inhibitory output signaling. Thus, persistent firing may emerge during conditions of intense activation of the network, thereby providing silencing to the circuitry and the maintenance of sparse activity in the dentate gyrus. Copyright © 2015 the authors 0270-6474/15/354131-09$15.00/0.

Modification of sodium and potassium channel kinetics by diethyl ether and studies on sodium channel inactivation in the crayfish giant axon membrane

Energy Technology Data Exchange (ETDEWEB)

Bean, Bruce Palmer [Univ. of Rochester, NY (United States)

1979-01-01

The effects of ether and halothane on membrane currents in the voltage clamped crayfish giant axon membrane were investigated. Concentrations of ether up to 300 mM and of halothane up to 32 mM had no effect on resting potential or leakage conductance. Ether and halothane reduced the size of sodium currents without changing the voltage dependence of the peak currents or their reversal potential. Ether and halothane also produced a reversible, dose-dependent speeding of sodium current decay at all membrane potentials. Ether reduced the time constants for inactivation, and also shifted the midpoint of the steady-state inactivation curve in the hyperpolarizing direction. Potassium currents were smaller with ether present, with no change in the voltage dependence of steady-state currents. The activation of potassium channels was faster with ether present. There was no apparent change in the capacitance of the crayfish giant axon membrane with ether concentrations of up to 100 mM. Experiments on sodium channel inactivation kinetics were performed using 4-aminopyridine to block potassium currents. Sodium currents decayed with a time course generally fit well by a single exponential. The time constant of decay was a steep function of voltage, especially in the negative resistance region of the peak current vs voltage relation.The time course of inactivation was very similar to that of the decay of the current at the same potential. The measurement of steady-state inactivation curves with different test pulses showed no shifts along the voltage asix. The voltage-dependence of the integral of sodium conductance was measured to test models of sodium channel inactivation in which channels must open before inactivating; the results appear inconsistent with some of the simplest cases of such models.

Inhibition of large conductance calcium-dependent potassium ...

African Journals Online (AJOL)

conductance, calcium and voltage- dependent potassium (BKCa) channels thereby promoting vasoconstriction. Our results show that the Rho-kinase inhibitor, Y-27632, induced concentration-dependent relaxation in rat mesenteric artery.

Lipopolysaccharide hyperpolarizes guinea pig airway epithelium by increasing the activities of the epithelial Na(+) channel and the Na(+)-K(+) pump.

Science.gov (United States)

Dodrill, Michael W; Fedan, Jeffrey S

2010-10-01

Earlier, we found that systemic administration of lipopolysaccharide (LPS; 4 mg/kg) hyperpolarized the transepithelial potential difference (V(t)) of tracheal epithelium in the isolated, perfused trachea (IPT) of the guinea pig 18 h after injection. As well, LPS increased the hyperpolarization component of the response to basolateral methacholine, and potentiated the epithelium-derived relaxing factor-mediated relaxation responses to hyperosmolar solutions applied to the apical membrane. We hypothesized that LPS stimulates the transepithelial movement of Na(+) via the epithelial sodium channel (ENaC)/Na(+)-K(+) pump axis, leading to hyperpolarization of V(t). LPS increased the V(t)-depolarizing response to amiloride (10 μM), i.e., offset the effect of LPS, indicating that Na(+) transport activity was increased. The functional activity of ENaC was measured in the IPT after short-circuiting the Na(+)-K(+) pump with basolateral amphotericin B (7.5 μM). LPS had no effect on the hyperpolarization response to apical trypsin (100 U/ml) in the Ussing chamber, indicating that channel-activating proteases are not involved in the LPS-induced activation of ENaC. To assess Na(+)-K(+) pump activity in the IPT, ENaC was short-circuited with apical amphotericin B. The greater V(t) in the presence of amphotericin B in tracheas from LPS-treated animals compared with controls revealed that LPS increased Na(+)-K(+) pump activity. This finding was confirmed in the Ussing chamber by inhibiting the Na(+)-K(+) pump via extracellular K(+) removal, loading the epithelium with Na(+), and observing a greater hyperpolarization response to K(+) restoration. Together, the findings of this study reveal that LPS hyperpolarizes the airway epithelium by increasing the activities of ENaC and the Na(+)-K(+) pump.

Hyperpolarized NMR Probes for Biological Assays

Directory of Open Access Journals (Sweden)

Sebastian Meier

2014-01-01

Full Text Available During the last decade, the development of nuclear spin polarization enhanced (hyperpolarized molecular probes has opened up new opportunities for studying the inner workings of living cells in real time. The hyperpolarized probes are produced ex situ, introduced into biological systems and detected with high sensitivity and contrast against background signals using high resolution NMR spectroscopy. A variety of natural, derivatized and designed hyperpolarized probes has emerged for diverse biological studies including assays of intracellular reaction progression, pathway kinetics, probe uptake and export, pH, redox state, reactive oxygen species, ion concentrations, drug efficacy or oncogenic signaling. These probes are readily used directly under natural conditions in biofluids and are often directly developed and optimized for cellular assays, thus leaving little doubt about their specificity and utility under biologically relevant conditions. Hyperpolarized molecular probes for biological NMR spectroscopy enable the unbiased detection of complex processes by virtue of the high spectral resolution, structural specificity and quantifiability of NMR signals. Here, we provide a survey of strategies used for the selection, design and use of hyperpolarized NMR probes in biological assays, and describe current limitations and developments.

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

Science.gov (United States)

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.

Alteration of sodium, potassium-adenosine triphosphatase activity in rabbit ciliary processes by cyclic adenosine monophosphate-dependent protein kinase

International Nuclear Information System (INIS)

Delamere, N.A.; Socci, R.R.; King, K.L.

1990-01-01

The response of sodium, potassium-adenosine triphosphatase (Na,K-ATPase) to cyclic adenosine monophosphate (cAMP)-dependent protein kinase was examined in membranes obtained from rabbit iris-ciliary body. In the presence of the protein kinase together with 10(-5) M cAMP, Na,K-ATPase activity was reduced. No change in Na,K-ATPase activity was detected in response to the protein kinase without added cAMP. Likewise cAMP alone did not alter Na,K-ATPase activity. Reduction of Na,K-ATPase activity was also observed in the presence of the cAMP-dependent protein kinase catalytic subunit. The response of the enzyme to the kinase catalytic subunit was also examined in membranes obtained from rabbit ciliary processes. In the presence of 8 micrograms/ml of the catalytic subunit, ciliary process Na,K-ATPase activity was reduced by more than 50%. To examine whether other ATPases were suppressed by the protein kinase, calcium-stimulated ATPase activity was examined; its activity was stimulated by the catalytic subunit. To test whether the response of the ciliary process Na,K-ATPase is unique, experiments were also performed using membrane preparations from rabbit lens epithelium or rabbit kidney; the catalytic subunit significantly reduced the activity of Na,K-ATPase from the kidney but not the lens. These Na,K-ATPase studies suggest that in the iris-ciliary body, cAMP may alter sodium pump activity. In parallel 86Rb uptake studies, we observed that ouabain-inhibitable potassium uptake by intact pieces of iris-ciliary body was reduced by exogenous dibutryl cAMP or by forskolin

Prostaglandin E2 EP2 and EP4 receptor activation mediates cAMP-dependent hyperpolarization and exocytosis of renin in juxtaglomerular cells

DEFF Research Database (Denmark)

Friis, Ulla Glenert; Stubbe, Jane; Uhrenholt, Torben Rene

2005-01-01

/l), AE1-259-01 (1 nmol/l), EP4-selective agonist AE1-329 (1 nmol/l), and IP agonist iloprost (1 micromol/l) significantly increased C(m) mediated by PKA. The EP4 antagonist AE3-208 (10 nmol/l) blocked the effect of EP4 agonist but did not alter the response to PGE(2). Application of both EP4 antagonist....... The membrane potential hyperpolarized significantly after PGE(2), butaprost, AE1-329 and AE1-259 and outward current was augmented in a PKA-dependent fashion. PGE(2)-stimulated outward current, but not C(m) change, was abolished by the BK(Ca) channel inhibitor iberiotoxin (300 nmol/l). EP2 and EP4 m......RNA was detected in sampled JG cells, and the preglomerular and glomerular vasculature was immunopositive for EP4. Thus IP, EP2, and EP4 receptors are associated with JG cells, and their activation leads to rapid PKA-mediated exocytotic fusion and release of renin granules....

Effects of potassium concentration on firing patterns of low-calcium epileptiform activity in anesthetized rat hippocampus: inducing of persistent spike activity.

Science.gov (United States)

Feng, Zhouyan; Durand, Dominique M

2006-04-01

It has been shown that a low-calcium high-potassium solution can generate ictal-like epileptiform activity in vitro and in vivo. Moreover, during status epileptiform activity, the concentration of [K+]o increases, and the concentration of [Ca2+]o decreases in brain tissue. Therefore we tested the hypothesis that long-lasting persistent spike activity, similar to one of the patterns of status epilepticus, could be generated by a high-potassium, low-calcium solution in the hippocampus in vivo. Artificial cerebrospinal fluid was perfused over the surface of the exposed left dorsal hippocampus of anesthetized rats. A stimulating electrode and a recording probe were placed in the CA1 region. By elevating K+ concentration from 6 to 12 mM in the perfusate solution, the typical firing pattern of low-calcium ictal bursts was transformed into persistent spike activity in the CA1 region with synaptic transmission being suppressed by calcium chelator EGTA. The activity was characterized by double spikes repeated at a frequency approximately 4 Hz that could last for >1 h. The analysis of multiple unit activity showed that both elevating [K+]o and lowering [Ca2+]o decreased the inhibition period after the response of paired-pulse stimulation, indicating a suppression of the after-hyperpolarization (AHP) activity. These results suggest that persistent status epilepticus-like spike activity can be induced by nonsynaptic mechanisms when synaptic transmission is blocked. The unique double-spike pattern of this activity is presumably caused by higher K+ concentration augmenting the frequency of typical low-calcium nonsynaptic burst activity.

Role of the activation gate in determining the extracellular potassium dependency of block of HERG by trapped drugs.

Science.gov (United States)

Pareja, Kristeen; Chu, Elaine; Dodyk, Katrina; Richter, Kristofer; Miller, Alan

2013-01-01

Drug induced long QT syndrome (diLQTS) results primarily from block of the cardiac potassium channel HERG (human-ether-a-go-go related gene). In some cases long QT syndrome can result in the lethal arrhythmia torsade de pointes, an arrhythmia characterized by a rapid heart rate and severely compromised cardiac output. Many patients requiring medication present with serum potassium abnormalities due to a variety of conditions including gastrointestinal dysfunction, renal and endocrine disorders, diuretic use, and aging. Extracellular potassium influences HERG channel inactivation and can alter block of HERG by some drugs. However, block of HERG by a number of drugs is not sensitive to extracellular potassium. In this study, we show that block of WT HERG by bepridil and terfenadine, two drugs previously shown to be trapped inside the HERG channel after the channel closes, is insensitive to extracellular potassium over the range of 0 mM to 20 mM. We also show that bepridil block of the HERG mutant D540K, a mutant channel that is unable to trap drugs, is dependent on extracellular potassium, correlates with the permeant ion, and is independent of HERG inactivation. These results suggest that the lack of extracellular potassium dependency of block of HERG by some drugs may in part be related to the ability of these drugs to be trapped inside the channel after the channel closes.

Potassium humate inhibits complement activation and the production of inflammatory cytokines in vitro

Energy Technology Data Exchange (ETDEWEB)

van Rensburg, C.E.J.; Naude, P.J. [University of Pretoria, Pretoria (South Africa)

2009-08-15

The effects of brown coal derived potassium humate on lymphocyte proliferation, cytokine production and complement activation were investigated in vitro. Potassium humate increased lymphocyte proliferation of phytohaemaglutinin A (PHA) and pokeweed mitogen (PWM) stimulated mononuclear lymphocytes (MNL) in vitro from concentrations of 20 to 80 {mu} g/ml, in a dose dependant manner. On the other hand potassium humate, at 40 {mu} g/ml, significantly inhibited the release of TNF-alpha, IL-1 beta, IL-6 and IL-10 by PHA stimulated MNL. Regarding complement activation it was found that potassium humate inhibits the activation of both the alternative and classical pathways without affecting the stability of the red blood cell membranes. These results indicate that the anti-inflammatory potential of potassium humate could be partially due to the inhibition of pro-inflammatory cytokines responsible for the initiation of these reactions as well as inhibition of complement activation. The increased lymphocyte proliferation observed, might be due to increased IL-2 production as previously been documented.

PIP2 mediates functional coupling and pharmacology of neuronal KCNQ channels

DEFF Research Database (Denmark)

Kim, Robin Y; Pless, Stephan A; Kurata, Harley T

2017-01-01

Retigabine (RTG) is a first-in-class antiepileptic drug that suppresses neuronal excitability through the activation of voltage-gated KCNQ2-5 potassium channels. Retigabine binds to the pore-forming domain, causing a hyperpolarizing shift in the voltage dependence of channel activation. To elucid......Retigabine (RTG) is a first-in-class antiepileptic drug that suppresses neuronal excitability through the activation of voltage-gated KCNQ2-5 potassium channels. Retigabine binds to the pore-forming domain, causing a hyperpolarizing shift in the voltage dependence of channel activation....... These findings reveal an important role for PIP2 in coupling retigabine binding to altered VSD function. We identify a polybasic motif in the proximal C terminus of retigabine-sensitive KCNQ channels that contributes to VSD-pore coupling via PIP2, and thereby influences the unique gating effects of retigabine....

Hyperpolarized metabolic MR in the study of cardiac function and disease

DEFF Research Database (Denmark)

Lauritzen, M. H.; Søgaard, L. V.; Madsen, Pia Lisbeth

2014-01-01

Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR...... signal from a biological molecule of interest by more than 10,000 times, making it possible to measure its cellular uptake and conversion in specific enzymatic pathways in real time. We review the role of hyperpolarized MR in identifying changes in cardiac metabolism in vivo, and present the extensive...... literature on hyperpolarized pyruvate that has been used to characterize cardiac disease in various in vivo models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and heart failure. The technical aspects of the technique are presented as well as the challenges of translating...

Molecular basis of potassium channels in pancreatic duct epithelial cells

DEFF Research Database (Denmark)

Hayashi, M.; Novak, Ivana

2013-01-01

Potassium channels regulate excitability, epithelial ion transport, proliferation, and apoptosis. In pancreatic ducts, K channels hyperpolarize the membrane potential and provide the driving force for anion secretion. This review focuses on the molecular candidates of functional K channels...... and pancreatic pathologies, including pancreatitis, cystic fibrosis, and cancer, in which the dysregulation or altered expression of K channels may be of importance....

Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.

Directory of Open Access Journals (Sweden)

Christian Albers

Full Text Available Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP. Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious and strong (teacher spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.

Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.

Science.gov (United States)

Albers, Christian; Westkott, Maren; Pawelzik, Klaus

2016-01-01

Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.

Dynamically Decoupled 13C Spins in Hyperpolarized Nanodiamond

Science.gov (United States)

Rej, Ewa; Gaebel, Torsten; Boele, Thomas; Waddington, David; Reilly, David

The spin-spin relaxation time, T2, which determines how long a quantum state remains coherent, is an important factor for many applications ranging from MRI to quantum computing. A common technique used in quantum information technology to extend the T2, involves averaging out certain noise spectra via dynamical decoupling sequences. Depending on the nature of the noise in the system, specific sequences, such as CPMG, UDD or KDD, can be tailored to optimize T2. Here we combine hyperpolarization techniques and dynamical decoupling sequences to extend the T2 of 13C nuclear spins in nanodiamond by three orders of magnitude.

Ovariectomy increases the participation of hyperpolarizing mechanisms in the relaxation of rat aorta.

Directory of Open Access Journals (Sweden)

Ana Sagredo

Full Text Available This study examines the downstream NO release pathway and the contribution of different vasodilator mediators in the acetylcholine-induced response in rat aorta 5-months after the loss of ovarian function. Aortic segments from ovariectomized and control female Sprague-Dawley rats were used to measure: the levels of superoxide anion, the superoxide dismutases (SODs activity, the cGMP formation, the cGMP-dependent protein kinase (PKG activity and the involvement of NO, cGMP, hydrogen peroxide and hyperpolarizing mechanisms in the ACh-induced relaxation. The results showed that ovariectomy did not alter ACh-induced relaxation; incubation with L-NAME, a NO synthase inhibitor, decreased the ACh-induced response to a lesser extent in aorta from ovariectomized than from control rats, while ODQ, a guanylate cyclase inhibitor, decreased that response to a similar extent; the blockade of hyperpolarizing mechanisms, by precontracting arteries with KCl, decreased the ACh-induced response to a greater extent in aortas from ovariectomized than those from control rats; catalase, that decomposes hydrogen peroxide, decreased the ACh-induced response only in aorta from ovariectomized rats. In addition, ovariectomy increased superoxide anion levels and SODs activity, decreased cGMP formation and increased PKG activity. Despite the increased superoxide anion and decreased cGMP in aorta from ovariectomized rats, ACh-induced relaxation is maintained by the existence of hyperpolarizing mechanisms in which hydrogen peroxide participates. The greater contribution of hydrogen peroxide in ACh-induced relaxation is due to increased SOD activity, in an attempt to compensate for increased superoxide anion formation. Increased PKG activity could represent a redundant mechanism to ensure vasodilator function in the aorta of ovariectomized rats.

Large-conductance calcium-dependent potassium channels prevent dendritic excitability in neocortical pyramidal neurons.

Science.gov (United States)

Benhassine, Narimane; Berger, Thomas

2009-03-01

Large-conductance calcium-dependent potassium channels (BK channels) are homogeneously distributed along the somatodendritic axis of layer 5 pyramidal neurons of the rat somatosensory cortex. The relevance of this conductance for dendritic calcium electrogenesis was studied in acute brain slices using somatodendritic patch clamp recordings and calcium imaging. BK channel activation reduces the occurrence of dendritic calcium spikes. This is reflected in an increased critical frequency of somatic spikes necessary to activate the distal initiation zone. Whilst BK channels repolarise the somatic spike, they dampen it only in the distal dendrite. Their activation reduces dendritic calcium influx via glutamate receptors. Furthermore, they prevent dendritic calcium electrogenesis and subsequent somatic burst discharges. However, the time window for coincident somatic action potential and dendritic input to elicit dendritic calcium events is not influenced by BK channels. Thus, BK channel activation in layer 5 pyramidal neurons affects cellular excitability primarily by establishing a high threshold at the distal action potential initiation zone.

Hyperpolarized Porous Silicon Nanoparticles: Potential Theragnostic Material for ²⁹Si Magnetic Resonance Imaging.

Science.gov (United States)

Seo, Hyeonglim; Choi, Ikjang; Whiting, Nicholas; Hu, Jingzhe; Luu, Quy Son; Pudakalakatti, Shivanand; McCowan, Caitlin; Kim, Yaewon; Zacharias, Niki; Lee, Seunghyun; Bhattacharya, Pratip; Lee, Youngbok

2018-05-20

Porous silicon nanoparticles have recently garnered attention as potentially-promising biomedical platforms for drug delivery and medical diagnostics. Here, we demonstrate porous silicon nanoparticles as contrast agents for ²⁹Si magnetic resonance imaging. Size-controlled porous silicon nanoparticles were synthesized by magnesiothermic reduction of silica nanoparticles and were surface activated for further functionalization. Particles were hyperpolarized via dynamic nuclear polarization to enhance their ²⁹Si MR signals; the particles demonstrated long ²⁹Si spin-lattice relaxation (T₁) times (~ 25 mins), which suggests potential applicability for medical imaging. Furthermore, ²⁹Si hyperpolarization levels were sufficient to allow ²⁹Si MRI in phantoms. These results underscore the potential of porous silicon nanoparticles that, when combined with hyperpolarized magnetic resonance imaging, can be a powerful theragnostic deep tissue imaging platform to interrogate various biomolecular processes in vivo. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dose and time-dependent effects of cyanide on thiosulfate sulfurtransferase, 3-mercaptopyruvate sulfurtransferase, and cystathionine λ-lyase activities.

Science.gov (United States)

Singh, Poonam; Rao, Pooja; Bhattacharya, Rahul

2013-12-01

We assessed the dose-dependent effect of potassium cyanide (KCN) on thiosulfate sulfurtransferase (TST), 3-mercaptopyruvate sulfurtransferase (3-MPST), and cystathionine λ-lyase (CST) activities in mice. The time-dependent effect of 0.5 LD50 KCN on cyanide level and cytochrome c oxidase (CCO), TST, 3-MPST, and CST activities was also examined. Furthermore, TST, 3-MPST, and CST activities were measured in stored mice cadavers. Hepatic and renal TST activity increased by 0.5 LD50 KCN but diminished by ≥2.0 LD50. After 0.5 LD50 KCN, the elevated hepatic cyanide level was accompanied by increased TST, 3-MPST, and CST activities, and CCO inhibition. Elevated renal cyanide level was only accompanied by increased 3-MPST activity. No appreciable change in enzyme activities was observed in mice cadavers. The study concludes that high doses of cyanide exert saturating effects on its detoxification enzymes, indicating their exogenous use during cyanide poisoning. Also, these enzymes are not reliable markers of cyanide poisoning in autopsied samples. © 2013 Wiley Periodicals, Inc.

Hyperpolarized Nanodiamond Surfaces.

Science.gov (United States)

Rej, Ewa; Gaebel, Torsten; Waddington, David E J; Reilly, David J

2017-01-11

The widespread use of nanodiamond as a biomedical platform for drug-delivery, imaging, and subcellular tracking applications stems from its nontoxicity and unique quantum mechanical properties. Here, we extend this functionality to the domain of magnetic resonance, by demonstrating that the intrinsic electron spins on the nanodiamond surface can be used to hyperpolarize adsorbed liquid compounds at low fields and room temperature. By combining relaxation measurements with hyperpolarization, spins on the surface of the nanodiamond can be distinguished from those in the bulk liquid. These results are likely of use in signaling the controlled release of pharmaceutical payloads.

Hyperpolarization-activated current (In is reduced in hippocampal neurons from Gabra5-/- mice.

Directory of Open Access Journals (Sweden)

Robert P Bonin

Full Text Available Changes in the expression of γ-aminobutyric acid type A (GABAA receptors can either drive or mediate homeostatic alterations in neuronal excitability. A homeostatic relationship between α5 subunit-containing GABAA (α5GABAA receptors that generate a tonic inhibitory conductance, and HCN channels that generate a hyperpolarization-activated cation current (Ih was recently described for cortical neurons, where a reduction in Ih was accompanied by a reciprocal increase in the expression of α5GABAA receptors resulting in the preservation of dendritosomatic synaptic function. Here, we report that in mice that lack the α5 subunit gene (Gabra5-/-, cultured embryonic hippocampal pyramidal neurons and ex vivo CA1 hippocampal neurons unexpectedly exhibited a decrease in Ih current density (by 40% and 28%, respectively, compared with neurons from wild-type (WT mice. The resting membrane potential and membrane hyperpolarization induced by blockade of Ih with ZD-7288 were similar in cultured WT and Gabra5-/- neurons. In contrast, membrane hyperpolarization measured after a train of action potentials was lower in Gabra5-/- neurons than in WT neurons. Also, membrane impedance measured in response to low frequency stimulation was greater in cultured Gabra5-/- neurons. Finally, the expression of HCN1 protein that generates Ih was reduced by 41% in the hippocampus of Gabra5-/- mice. These data indicate that loss of a tonic GABAergic inhibitory conductance was followed by a compensatory reduction in Ih. The results further suggest that the maintenance of resting membrane potential is preferentially maintained in mature and immature hippocampal neurons through the homeostatic co-regulation of structurally and biophysically distinct cation and anion channels.

Kidney in potassium depletion. I. Na+-K+-ATPase activity and [3H]ouabain binding in MCT

International Nuclear Information System (INIS)

Hayashi, M.; Katz, A.I.

1987-01-01

The effect of potassium depletion on renal Na + K + -ATPase was studied in rats. K depletion produced a striking, time-dependent increase in Na + -K + -ATPase activity of the outer medullary collecting tubules (inner stripe; MCT/sub is/). After 3 wk on the K-free diet, when the urine was almost potassium-free, Na + -K + -ATPase activity in MCT/sub is/ was over fourfold higher than in control animals. Repletion of potassium restored enzyme activity to base line within 7 days which corresponds to the catabolic rate of the renal enzyme, suggesting the cessation of enhanced synthesis that took place during K deprivation. Changes in Na + -K + -ATPase activity and aldosterone levels during both K depletion and repletion occurred in opposite directions and were therefore independent of each other. [ 3 H]Ouabain binding to intact MCT/sub is/, reflecting the number of pump sites on the basolateral membrane, was similar in K-depleted and control animals; in contrast, tubule permeabilization that exposes additional pump units to the ligand, unmasked a nearly fourfold increase in [ 3 H]ouabain binding in K-depleted rats, comparable to the increment in Na + -K + -ATPase activity. These results show that K depletion leads to a marked increase in Na + -K + -ATPase activity of MCT/sub is/, and suggest that the new enzyme units are located at a ouabain-inaccessible site in the intact tubule, i.e., either in an intracellular compartment or at the luminal membrane, where they may be involved in potassium reabsorption

Ionic channels and membrane hyperpolarization in human macrophages

NARCIS (Netherlands)

Ince, C.; van Duijn, B.; Ypey, D. L.; van Bavel, E.; Weidema, F.; Leijh, P. C.

1987-01-01

Microelectrode impalement of human macrophages evokes a transient hyperpolarizing response (HR) of the membrane potential. This HR was found to be dependent on the extracellular concentration of K+ but not on that of Na+ or Cl-. It was not influenced by low temperature (12 degrees C) or by 0.2 mM

Dynamic coronary MR angiography in a pig model with hyperpolarized water

DEFF Research Database (Denmark)

Lipsø, Hans Kasper Wigh; Hansen, Esben Søvsø Szocska; Tougaard, Rasmus Stilling

2018-01-01

To investigate dynamic coronary MR angiography using hyperpolarized water as a positive contrast agent. Hyperpolarization can increase the signal by several orders of magnitude, and has recently been translated to human cardiac application. The aim was to achieve large 1 H signal enhancement...... to allow high-resolution imaging of the coronary arteries. Protons in D2 O were hyperpolarized by dissolution dynamic nuclear polarization. A total of 18 mL of hyperpolarized water was injected into the coronary arteries of healthy pigs (N = 9; 3 injections in 3 animals). The MRI images were acquired...... with a gradient-echo sequence in an oblique slab covering the main left coronary arteries with 0.55 mm in-plane resolution. The acquisition time was 870 ms per frame. A more than 200-fold signal enhancement compared with thermally polarized water at 3 T was obtained. Coronary angiographic images with a signal...

Importance of large conductance calcium-activated potassium channels (BKCa) in interleukin-1b-induced adhesion of monocytes to endothelial cells.

Science.gov (United States)

Burgazli, K M; Venker, C J; Mericliler, M; Atmaca, N; Parahuleva, M; Erdogan, A

2014-01-01

The present study investigated the role of the large conductance calcium-activated potassium channels (BKCa) in interleukin-1b (IL-1b) induced inflammation. Human umbilical vein endothelial cells (HUVECs) were isolated and cultured. Endothelial cell membrane potential measurements were accomplished using the fluorescent dye DiBAC4(3). The role of BKCa was assessed using iberiotoxin, a highly selective BKCa inhibitor. Changes in the calcium intracellular calcium were investigated using Fura-2-AM imaging. Fluorescent dyes DCF-AM and DAF-AM were further used in order to measure the formation of reactive oxygen species (ROS) and nitric oxide (NO) synthesis, respectively. Endothelial cell adhesion tests were conducted with BCECF-AM adhesion assay and tritium thymidine uptake using human monocytic cells (U937). Expression of cellular adhesion molecules (ICAM-1, VCAM-1) was determined by flow cytometer. Interleukin-1b induced a BKCa dependent hyperpolarization of HUVECs. This was followed by an increase in the intracellular calcium concentration. Furthermore, IL-1b significantly increased the synthesis of NO and ROS. The increase of intracellular calcium, radicals and NO resulted in a BKCa dependent adhesion of monocytes to HUVECs. Endothelial cells treated with IL-1b expressed both ICAM-1 and VCAM-1 in significantly higher amounts as when compared to controls. It was further shown that the cellular adhesion molecules ICAM-1 and VCAM-1 were responsible for the BKCa-dependent increase in cellular adhesion. Additionally, inhibition of the NADPH oxidase with DPI led to a significant downregulation of IL-1b-induced expression of ICAM and VCAM, as well as inhibition of eNOS by L-NMMA, and intracellular calcium by BAPTA. Activation of the endothelial BKCa plays an important role in the IL-1b-induced monocyte adhesion to endothelial cells.

Pressure dependence of the interfacial structure of potassium chloride films on iron

International Nuclear Information System (INIS)

Olson, Dustin; Gao, Hongyu; Tang, Chun; Tysoe, Wilfred T.; Martini, Ashlie

2015-01-01

Potassium chloride films on a clean iron surface are used as a model system to explore the interfacial structure of the films and the dependence of that structure on film thickness and pressure. The interfacial structure of one-, two-, three- and four-layer films is measured experimentally using low-energy electron diffraction. Those findings are then complemented by molecular dynamics simulations in which the atomic interaction between the film and substrate is tuned to match film thickness-dependent sublimation activation energy obtained from temperature-programmed desorption measurements. The resultant simulation reliably predicts the structure of thicker films and is then used to study the effect of pressure on the distribution of the lattice constant within and between each layer of the potassium chloride films. Findings indicate that both film thickness and pressure affect the structure within the films as well as the degree of registry between the film and adjacent substrate. - Highlights: • KCl films on an Fe surface are used as a model system to explore interfacial structure • Thin film structure is measured using low-energy electron diffraction • An empirical potential is tuned to match sublimation activation energy • Simulations reveal the effect of pressure on the lattice constant within the KCl films • Pressure affects the film structure and registry between film and substrate

Pressure dependence of the interfacial structure of potassium chloride films on iron

Energy Technology Data Exchange (ETDEWEB)

Olson, Dustin [Department of Chemistry and Laboratory for Surface Studies, University of Wisconsin—Milwaukee, Milwaukee, WI 53211 (United States); Gao, Hongyu; Tang, Chun [School of Engineering, University of California Merced, Merced CA 95343 (United States); Tysoe, Wilfred T. [Department of Chemistry and Laboratory for Surface Studies, University of Wisconsin—Milwaukee, Milwaukee, WI 53211 (United States); Martini, Ashlie [School of Engineering, University of California Merced, Merced CA 95343 (United States)

2015-10-30

Potassium chloride films on a clean iron surface are used as a model system to explore the interfacial structure of the films and the dependence of that structure on film thickness and pressure. The interfacial structure of one-, two-, three- and four-layer films is measured experimentally using low-energy electron diffraction. Those findings are then complemented by molecular dynamics simulations in which the atomic interaction between the film and substrate is tuned to match film thickness-dependent sublimation activation energy obtained from temperature-programmed desorption measurements. The resultant simulation reliably predicts the structure of thicker films and is then used to study the effect of pressure on the distribution of the lattice constant within and between each layer of the potassium chloride films. Findings indicate that both film thickness and pressure affect the structure within the films as well as the degree of registry between the film and adjacent substrate. - Highlights: • KCl films on an Fe surface are used as a model system to explore interfacial structure • Thin film structure is measured using low-energy electron diffraction • An empirical potential is tuned to match sublimation activation energy • Simulations reveal the effect of pressure on the lattice constant within the KCl films • Pressure affects the film structure and registry between film and substrate.

Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

DEFF Research Database (Denmark)

Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

2010-01-01

This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...... (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK...

Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease.

Science.gov (United States)

Poulopoulou, Cornelia; Markakis, Ioannis; Davaki, Panagiota; Tsaltas, Eleftheria; Rombos, Antonis; Hatzimanolis, Alexandros; Vassilopoulos, Dimitrios

2010-02-01

In Alzheimer's disease (AD), potassium channel abnormalities have been reported in both neural and peripheral tissues. Herein, using whole-cell patch-clamp, we demonstrate an aberrant glutamate-dependent modulation of K(V)1.3 channels in T lymphocytes of AD patients. Although intrinsic K(V)1.3 properties in patients were similar to healthy individuals, glutamate (1-1000 microM) failed to yield the hyperpolarizing shift normally observed in K(V)1.3 steady-state inactivation (-4.4+/-2.7 mV in AD vs. -14.3+/-2.5 mV in controls, 10 microM glutamate), resulting in a 4-fold increase of resting channel activity. Specific agonist and antagonist data indicate that this abnormality is due to dysfunction of cognate group II mGluRs. Given that glutamate is present in plasma and that both mGluRs and K(V)1.3 channels regulate T-lymphocyte responsiveness, our finding may account for the presence of immune-associated alterations in AD. Furthermore, if this aberration reflects a corresponding one in neural tissue, it could provide a potential target in AD pathogenesis.

ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells.

Science.gov (United States)

Poppi, Lauren A; Tabatabaee, Hessam; Drury, Hannah R; Jobling, Phillip; Callister, Robert J; Migliaccio, Americo A; Jordan, Paivi M; Holt, Joseph C; Rabbitt, Richard D; Lim, Rebecca; Brichta, Alan M

2018-01-01

In the mammalian vestibular periphery, electrical activation of the efferent vestibular system (EVS) has two effects on afferent activity: 1) it increases background afferent discharge and 2) decreases afferent sensitivity to rotational stimuli. Although the cellular mechanisms underlying these two contrasting afferent responses remain obscure, we postulated that the reduction in afferent sensitivity was attributed, in part, to the activation of α9- containing nicotinic acetylcholine (ACh) receptors (α9*nAChRs) and small-conductance potassium channels (SK) in vestibular type II hair cells, as demonstrated in the peripheral vestibular system of other vertebrates. To test this hypothesis, we examined the effects of the predominant EVS neurotransmitter ACh on vestibular type II hair cells from wild-type (wt) and α9-subunit nAChR knockout (α9 -/- ) mice. Immunostaining for choline acetyltransferase revealed there were no obvious gross morphological differences in the peripheral EVS innervation among any of these strains. ACh application onto wt type II hair cells, at resting potentials, produced a fast inward current followed by a slower outward current, resulting in membrane hyperpolarization and decreased membrane resistance. Hyperpolarization and decreased resistance were due to gating of SK channels. Consistent with activation of α9*nAChRs and SK channels, these ACh-sensitive currents were antagonized by the α9*nAChR blocker strychnine and SK blockers apamin and tamapin. Type II hair cells from α9 -/- mice, however, failed to respond to ACh at all. These results confirm the critical importance of α9nAChRs in efferent modulation of mammalian type II vestibular hair cells. Application of exogenous ACh reduces electrical impedance, thereby decreasing type II hair cell sensitivity. NEW & NOTEWORTHY Expression of α9 nicotinic subunit was crucial for fast cholinergic modulation of mammalian vestibular type II hair cells. These findings show a multifaceted

Voltage-dependent gating of hERG potassium channels

Directory of Open Access Journals (Sweden)

Yen May eCheng

2012-05-01

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

Chronic potassium depletion increases adrenal progesterone production that is necessary for efficient renal retention of potassium.

Science.gov (United States)

Elabida, Boutaïna; Edwards, Aurélie; Salhi, Amel; Azroyan, Anie; Fodstad, Heidi; Meneton, Pierre; Doucet, Alain; Bloch-Faure, May; Crambert, Gilles

2011-08-01

Modern dietary habits are characterized by high-sodium and low-potassium intakes, each of which was correlated with a higher risk for hypertension. In this study, we examined whether long-term variations in the intake of sodium and potassium induce lasting changes in the plasma concentration of circulating steroids by developing a mathematical model of steroidogenesis in mice. One finding of this model was that mice increase their plasma progesterone levels specifically in response to potassium depletion. This prediction was confirmed by measurements in both male mice and men. Further investigation showed that progesterone regulates renal potassium handling both in males and females under potassium restriction, independent of its role in reproduction. The increase in progesterone production by male mice was time dependent and correlated with decreased urinary potassium content. The progesterone-dependent ability to efficiently retain potassium was because of an RU486 (a progesterone receptor antagonist)-sensitive stimulation of the colonic hydrogen, potassium-ATPase (known as the non-gastric or hydrogen, potassium-ATPase type 2) in the kidney. Thus, in males, a specific progesterone concentration profile induced by chronic potassium restriction regulates potassium balance.

Effect of potassium ferrate on disintegration of waste activated sludge (WAS).

Science.gov (United States)

Ye, Fenxia; Ji, Haizhuang; Ye, Yangfang

2012-06-15

The activated sludge process of wastewater treatment results in the generation of a considerable amount of excess activated sludge. Increased attention has been given to minimization of waste activated sludge recently. This paper investigated the effect of potassium ferrate oxidation pretreatment on the disintegration of the waste activated sludge at various dosages of potassium ferrate. The results show that potassium ferrate pretreatment disintegrated the sludge particle, resulting in the reduction of total solid content by 31%. The solubility (SCOD/TCOD) of the sludge increased with the increase of potassium ferrate dosage. Under 0.81 g/g SS dosage of potassium ferrate, SCOD/TCOD reached 0.32. Total nitrogen (TN) and total phosphorous (TP) concentrations in the solution all increased significantly after potassium ferrate pretreatment. The sludge particles reduced from 116 to 87 μm. The settleability of the sludge (SVI) was enhanced by 17%, which was due to the re-flocculation by the by-product, Fe(III), during potassium ferrate oxidation and the decrease of the viscosity. From the result of the present investigations, it can be concluded that potassium ferrate oxidation is a feasible method for disintegration of excess activated sludge. Copyright © 2012 Elsevier B.V. All rights reserved.

Alcohol and the calcium-dependent potassium transport of human erythrocytes

International Nuclear Information System (INIS)

Harris, R.A.; Caldwell, K.K.

1985-01-01

In vitro exposure of human red blood cells to ethanol (100 and 400 mM) was found to increase the initial rate of calcium-dependent potassium efflux through the red cell membrane. This effect of ethanol was apparently not due to an elevation of the intracellular free calcium but rather to a direct action of the drug on the transport process as, (1) intracellular calcium concentrations were tightly buffered with EGTA, (2) ethanol did not alter the efflux of 45 Ca from the cells, and (3) dantrolene, which has been proposed to counteract the effect of ethanol on intracellular calcium levels in the erythrocyte, did not inhibit the stimulatory action of ethanol. The efflux of potassium from erythrocytes obtained from chronic alcoholics was not different from that of erythrocytes from non-alcoholic individuals. The relationship of these findings to neuronal potassium transport is discussed

Inward rectifier potassium currents in mammalian skeletal muscle fibres

Science.gov (United States)

DiFranco, Marino; Yu, Carl; Quiñonez, Marbella; Vergara, Julio L

2015-01-01

Inward rectifying potassium (Kir) channels play a central role in maintaining the resting membrane potential of skeletal muscle fibres. Nevertheless their role has been poorly studied in mammalian muscles. Immunohistochemical and transgenic expression were used to assess the molecular identity and subcellular localization of Kir channel isoforms. We found that Kir2.1 and Kir2.2 channels were targeted to both the surface andthe transverse tubular system membrane (TTS) compartments and that both isoforms can be overexpressed up to 3-fold 2 weeks after transfection. Inward rectifying currents (IKir) had the canonical features of quasi-instantaneous activation, strong inward rectification, depended on the external [K+], and could be blocked by Ba2+ or Rb+. In addition, IKir records show notable decays during large 100 ms hyperpolarizing pulses. Most of these properties were recapitulated by model simulations of the electrical properties of the muscle fibre as long as Kir channels were assumed to be present in the TTS. The model also simultaneously predicted the characteristics of membrane potential changes of the TTS, as reported optically by a fluorescent potentiometric dye. The activation of IKir by large hyperpolarizations resulted in significant attenuation of the optical signals with respect to the expectation for equal magnitude depolarizations; blocking IKir with Ba2+ (or Rb+) eliminated this attenuation. The experimental data, including the kinetic properties of IKir and TTS voltage records, and the voltage dependence of peak IKir, while measured at widely dissimilar bulk [K+] (96 and 24 mm), were closely predicted by assuming Kir permeability (PKir) values of ∼5.5 × 10−6 cm s−1 and equal distribution of Kir channels at the surface and TTS membranes. The decay of IKir records and the simultaneous increase in TTS voltage changes were mostly explained by K+ depletion from the TTS lumen. Most importantly, aside from allowing an accurate estimation of

Phase dependency of electrotonic spread of hyperpolarizing current pulses in the rabbit sinoatrial node

NARCIS (Netherlands)

Duivenvoorden, J. J.; Bouman, L. N.; Bukauskas, F. F.; Opthof, T.; Jongsma, H. J.

1990-01-01

Electrotonic current spread in the SA node of the rabbit was measured by means of hyperpolarizing current pulses (1 to 10 microA, 60 ms), which were injected intracellularly through a K(+)-perfused suction electrode. The pulses were applied at the beginning, middle or end of the diastolic

Reduced Hyperpolarization-Activated Current Contributes to Enhanced Intrinsic Excitability in Cultured Hippocampal Neurons from PrP(-/-) Mice.

Science.gov (United States)

Fan, Jing; Stemkowski, Patrick L; Gandini, Maria A; Black, Stefanie A; Zhang, Zizhen; Souza, Ivana A; Chen, Lina; Zamponi, Gerald W

2016-01-01

Genetic ablation of cellular prion protein (PrP(C)) has been linked to increased neuronal excitability and synaptic activity in the hippocampus. We have previously shown that synaptic activity in hippocampi of PrP-null mice is increased due to enhanced N-methyl-D-aspartate receptor (NMDAR) function. Here, we focused on the effect of PRNP gene knock-out (KO) on intrinsic neuronal excitability, and in particular, the underlying ionic mechanism in hippocampal neurons cultured from P0 mouse pups. We found that the absence of PrP(C) profoundly affected the firing properties of cultured hippocampal neurons in the presence of synaptic blockers. The membrane impedance was greater in PrP-null neurons, and this difference was abolished by the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288 (100 μM). HCN channel activity appeared to be functionally regulated by PrP(C). The amplitude of voltage sag, a characteristic of activating HCN channel current (I h), was decreased in null mice. Moreover, I h peak current was reduced, along with a hyperpolarizing shift in activation gating and slower kinetics. However, neither HCN1 nor HCN2 formed a biochemical complex with PrP(C). These results suggest that the absence of PrP downregulates the activity of HCN channels through activation of a cell signaling pathway rather than through direct interactions. This in turn contributes to an increase in membrane impedance to potentiate neuronal excitability.

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.

Design of a 15N Molecular Unit to Achieve Long Retention of Hyperpolarized Spin State

Science.gov (United States)

Nonaka, Hiroshi; Hirano, Masashi; Imakura, Yuki; Takakusagi, Yoichi; Ichikawa, Kazuhiro; Sando, Shinsuke

2017-01-01

Nuclear hyperpolarization is a phenomenon that can be used to improve the sensitivity of magnetic resonance molecular sensors. However, such sensors typically suffer from short hyperpolarization lifetime. Herein we report that [15N, D14]trimethylphenylammonium (TMPA) has a remarkably long spin-lattice relaxation time (1128 s, 14.1 T, 30 °C, D2O) on its 15N nuclei and achieves a long retention of the hyperpolarized state. [15N, D14]TMPA-based hyperpolarized sensor for carboxylesterase allowed the highly sensitive analysis of enzymatic reaction by 15N NMR for over 40 min in phophate-buffered saline (H2O, pH 7.4, 37 °C).

A magnetic tunnel to shelter hyperpolarized fluids

International Nuclear Information System (INIS)

Milani, Jonas; Vuichoud, Basile; Bornet, Aurélien; Miéville, Pascal; Mottier, Roger; Jannin, Sami; Bodenhausen, Geoffrey

2015-01-01

To shield solutions carrying hyperpolarized nuclear magnetization from rapid relaxation during transfer through low fields, the transfer duct can be threaded through an array of permanent magnets. The advantages are illustrated for solutions containing hyperpolarized 1 H and 13 C nuclei in a variety of molecules

A magnetic tunnel to shelter hyperpolarized fluids

Energy Technology Data Exchange (ETDEWEB)

Milani, Jonas, E-mail: jonas.milani@epfl.ch; Vuichoud, Basile; Bornet, Aurélien; Miéville, Pascal; Mottier, Roger [Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), Batochime, CH-1015 Lausanne (Switzerland); Jannin, Sami [Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), Batochime, CH-1015 Lausanne (Switzerland); Bruker BioSpin AG, Industriestrasse 26, CH-8117 Fällanden (Switzerland); Bodenhausen, Geoffrey [Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), Batochime, CH-1015 Lausanne (Switzerland); Département de Chimie, École Normale Supérieure-PSL Research University, 24 rue Lhomond, F-75005 Paris (France); Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 place Jussieu, F-75005 Paris (France); CNRS, UMR 7203 LBM, F-75005 Paris (France)

2015-02-15

To shield solutions carrying hyperpolarized nuclear magnetization from rapid relaxation during transfer through low fields, the transfer duct can be threaded through an array of permanent magnets. The advantages are illustrated for solutions containing hyperpolarized {sup 1}H and {sup 13}C nuclei in a variety of molecules.

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

Directory of Open Access Journals (Sweden)

Seong-Ho Ok

2013-01-01

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

Voltage-Dependent Gating of hERG Potassium Channels

Science.gov (United States)

Cheng, Yen May; Claydon, Tom W.

2012-01-01

The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv) channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4–S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-à-go-go related gene, hERG), which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure–function relationships underlying activation and deactivation gating in Shaker and hERG channels, with a focus on the roles of the voltage-sensing domain and the S4–S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter-charge interactions. More recent data suggest that key amino acid differences in the hERG voltage-sensing unit and S4–S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor. PMID:22586397

Kidney in potassium depletion. I. Na/sup +/-K/sup +/-ATPase activity and (/sup 3/H)ouabain binding in MCT

Energy Technology Data Exchange (ETDEWEB)

Hayashi, M.; Katz, A.I.

1987-03-01

The effect of potassium depletion on renal Na/sup +/K/sup +/-ATPase was studied in rats. K depletion produced a striking, time-dependent increase in Na/sup +/-K/sup +/-ATPase activity of the outer medullary collecting tubules (inner stripe; MCT/sub is/). After 3 wk on the K-free diet, when the urine was almost potassium-free, Na/sup +/-K/sup +/-ATPase activity in MCT/sub is/ was over fourfold higher than in control animals. Repletion of potassium restored enzyme activity to base line within 7 days which corresponds to the catabolic rate of the renal enzyme, suggesting the cessation of enhanced synthesis that took place during K deprivation. Changes in Na/sup +/-K/sup +/-ATPase activity and aldosterone levels during both K depletion and repletion occurred in opposite directions and were therefore independent of each other. (/sup 3/H)Ouabain binding to intact MCT/sub is/, reflecting the number of pump sites on the basolateral membrane, was similar in K-depleted and control animals; in contrast, tubule permeabilization that exposes additional pump units to the ligand, unmasked a nearly fourfold increase in (/sup 3/H)ouabain binding in K-depleted rats, comparable to the increment in Na/sup +/-K/sup +/-ATPase activity. These results show that K depletion leads to a marked increase in Na/sup +/-K/sup +/-ATPase activity of MCT/sub is/, and suggest that the new enzyme units are located at a ouabain-inaccessible site in the intact tubule, i.e., either in an intracellular compartment or at the luminal membrane, where they may be involved in potassium reabsorption.

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

Role of endothelium-derived hyperpolarization in the vasodilatation of rat intrarenal arteries

DEFF Research Database (Denmark)

Pinilla, Estéfano; Sánchez-Pina, Ana; Muñoz Picos, Mercedes

2016-01-01

Background and purpose: Endothelium-dependent vasodilation plays an important role in the regulation of vascular tone in different vascular beds. Besides the release of prostacyclin (PGI2) and nitric oxide (NO), the endothelium mediates vasodilation through endothelium-derived hyperpolarization (...

Hyperpolarized H2O MR angiography

DEFF Research Database (Denmark)

Ardenkjær-Larsen, Jan Henrik; Laustsen, Christoffer; Bowen, Sean

2014-01-01

polarization followed by dissolution in D2O. A water 1H signal enhancement of 77 times compared with 4.7 Tesla was obtained. This corresponds to a polarization of 3.5% for the 3.9 mol/L 1H in D2O . Moreover, a T1 in excess of 20 s was achieved. The use of hyperpolarized water as a contrast agent presents a new...

Effect of membrane hyperpolarization induced by a K+ channel opener on histamine-induced Ca2+ mobilization in rabbit arterial smooth muscle.

Science.gov (United States)

Watanabe, Y; Suzuki, A; Suzuki, H; Itoh, T

1996-03-01

-toxin-skinned smooth muscles. 5. It is concluded that the membrane hyperpolarization induced by Y-26763 may not be enough to inhibit the Hist-activated Ca2+ influx. It is also suggested that Hist prevents the membrane hyperpolarization induced by Y-26763, activating an unknown mechanism which is thought to depend on the function of intracellular Ca2+ storage sites.

Pharmacological activation of rapid delayed rectifier potassium current suppresses bradycardia-induced triggered activity in the isolated guinea pig heart

DEFF Research Database (Denmark)

Hansen, Rie Schultz; Olesen, Søren-Peter; Grunnet, Morten

2007-01-01

arrhythmias. We present here data that support that NS3623 affects native I(Kr) and report the effects that activating this potassium current have in the intact guinea pig heart. In Langendorff-perfused hearts, the compound showed a concentration-dependent shortening of action potential duration, which...

Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

Science.gov (United States)

Yang, Li-Zhen; Zhu, Yi-Chun

2015-07-05

We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmacological Conversion of a Cardiac Inward Rectifier into an Outward Rectifier Potassium Channel.

Science.gov (United States)

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

2016-09-01

Potassium (K(+)) channels are crucial for determining the shape, duration, and frequency of action-potential firing in excitable cells. Broadly speaking, K(+) channels can be classified based on whether their macroscopic current outwardly or inwardly rectifies, whereby rectification refers to a change in conductance with voltage. Outwardly rectifying K(+) channels conduct greater current at depolarized membrane potentials, whereas inward rectifier channels conduct greater current at hyperpolarized membrane potentials. Under most circumstances, outward currents through inwardly rectifying K(+) channels are reduced at more depolarized potentials. However, the acetylcholine-gated K(+) channel (KACh) conducts current that inwardly rectifies when activated by some ligands (such as acetylcholine), and yet conducts current that outwardly rectifies when activated by other ligands (for example, pilocarpine and choline). The perplexing and paradoxical behavior of KACh channels is due to the intrinsic voltage sensitivity of the receptor that activates KACh channels, the M2 muscarinic receptor (M2R). Emerging evidence reveals that the affinity of M2R for distinct ligands varies in a voltage-dependent and ligand-specific manner. These intrinsic receptor properties determine whether current conducted by KACh channels inwardly or outwardly rectifies. This review summarizes the most recent concepts regarding the intrinsic voltage sensitivity of muscarinic receptors and the consequences of this intriguing behavior on cardiac physiology and pharmacology of KACh channels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Space-Time Dependent Transport, Activation, and Dose Rates for Radioactivated Fluids.

Science.gov (United States)

Gavazza, Sergio

Two methods are developed to calculate the space - and time-dependent mass transport of radionuclides, their production and decay, and the associated dose rates generated from the radioactivated fluids flowing through pipes. The work couples space- and time-dependent phenomena, treated as only space- or time-dependent in the open literature. The transport and activation methodology (TAM) is used to numerically calculate space- and time-dependent transport and activation of radionuclides in fluids flowing through pipes exposed to radiation fields, and volumetric radioactive sources created by radionuclide motions. The computer program Radionuclide Activation and Transport in Pipe (RNATPA1) performs the numerical calculations required in TAM. The gamma ray dose methodology (GAM) is used to numerically calculate space- and time-dependent gamma ray dose equivalent rates from the volumetric radioactive sources determined by TAM. The computer program Gamma Ray Dose Equivalent Rate (GRDOSER) performs the numerical calculations required in GAM. The scope of conditions considered by TAM and GAM herein include (a) laminar flow in straight pipe, (b)recirculating flow schemes, (c) time-independent fluid velocity distributions, (d) space-dependent monoenergetic neutron flux distribution, (e) space- and time-dependent activation process of a single parent nuclide and transport and decay of a single daughter radionuclide, and (f) assessment of space- and time-dependent gamma ray dose rates, outside the pipe, generated by the space- and time-dependent source term distributions inside of it. The methodologies, however, can be easily extended to include all the situations of interest for solving the phenomena addressed in this dissertation. A comparison is made from results obtained by the described calculational procedures with analytical expressions. The physics of the problems addressed by the new technique and the increased accuracy versus non -space and time-dependent methods

Anoxia increases potassium conductance in hippocampal nerve cells.

Science.gov (United States)

Hansen, A J; Hounsgaard, J; Jahnsen, H

1982-07-01

The effect of anoxia on nerve cell function was studied by intra- and extracellular microelectrode recordings from the CA1 and CA3 region in guinea pig hippocampal slices. Hyperpolarization and concomitant reduction of the nerve cell input resistance was observed early during anoxia. During this period the spontaneous activity first disappeared, then the evoked activity gradually disappeared. The hyperpolarization was followed by depolarization and an absence of a measurable input resistance. All the induced changes were reversed when the slice was reoxygenated. Reversal of the electro-chemical gradient for Cl- across the nerve cell membrane did not affect the course of events during anoxia. Aminopyridines blocked the anoxic hyperpolarization and attenuated the decrease of membrane resistance, but had no effect on the later depolarization. Blockers of synaptic transmission. Mn++, Mg++ and of Na+-channels (TTX) were without effect on the nerve cell changes during anoxia. It is suggested that the reduction of nerve cell excitability in anoxia is primarily due to increased K+-conductance. Thus, the nerve cells are hyperpolarized and the input resistance reduced, causing higher threshold and reduction of synaptic potentials. The mechanism of the K+-conductance activation is unknown at present.

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.

Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance

DEFF Research Database (Denmark)

Brazhe, Alexey; Maksimov, G. V.; Mosekilde, Erik

2011-01-01

. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes...... in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from...

Interacting influence of potassium and polychlorinated biphenyl on cortisol and aldosterone biosynthesis

International Nuclear Information System (INIS)

Li, L.-A.; Lin, Tsu-Chun Emma

2007-01-01

Giving human adrenocortical H295R cells 14 mM KCl for 24 h significantly induced not only aldosterone biosynthesis but also cortisol biosynthesis. Pre-treating the cells with polychlorinated biphenyl 126 (PCB126) further increased potassium-induced aldosterone and cortisol productions in a dose-dependent manner, but all examined concentrations of PCB126 had little effect on the yields of precursor steroids progesterone and 17-OH-progesterone. Subsequent examinations revealed that CYP11B1 and CYP11B2 genes, responsible for the respective final steps of the cortisol and aldosterone biosynthetic pathways, exhibited increased responsiveness to PCB126 under high potassium. While 10 -5 M PCB126 was needed to induce a significant increase in the basal mRNA abundance of either gene, PCB126 could enhance potassium-induced mRNA expression of CYP11B1 at 10 -7 M and CYP11B2 at 10 -9 M. Actually, potassium and PCB126 synergistically upregulated mRNA expression of both genes. Potassium raised the transcriptional rates of CYP11B1 and CYP11B2 probably through a conserved Ad5 cis-element, whereas PCB126 appeared to regulate these two genes at the post-transcriptional level. Positive potassium-PCB126 synergism was also detected in CYP11B2 enzyme activity estimated by aldosterone/progesterone ratio. In contrast, potassium and PCB126 increased CYP11B1 enzyme activity or cortisol/17-OH-progesterone ratio additively. Moreover, potassium improved the time effect of PCB126 on gene expression and enzyme activity of CYP11B2, but not the PCB126 time response of CYP11B1. These data demonstrated that potassium differentially enhanced the potency of PCB126 to induce CYP11B1- and CYP11B2-mediated steroidogenesis

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

Directory of Open Access Journals (Sweden)

Salmela Iikka

2012-08-01

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

Echo-planar MR imaging of dissolved hyperpolarized 129Xe. Potential for M angiography

International Nuclear Information System (INIS)

Maansson, S.

2002-01-01

Purpose: The feasibility of hyperpolarized 129 Xe for fast MR angiography (MRA) was evaluated using the echo-planar imaging (EPI) technique. Material and Methods: Hyperpolarized Xe gas was dissolved in ethanol; a carrier agent with high solubility for Xe (Ostwald solubility coefficient 2.5) and long relaxation times. The dissolved Xe was injected as a bolus into a flow phantom where the mean flow velocity was 15 cm/s. Ultrafast EPI images with 44 ms scan time were acquired of the flowing bolus and the signal-to-noise ratios (SNR) were measured. Results: The relaxation times of hyperpolarized Xe in ethanol were measured to T1=160±11 s and T2 ≅ 20 s. The resulting images of the flowing liquid were of reasonable quality and had an SNR of about 70. Conclusion: Based on the SNR of the obtained Xe EPI images; it was estimated that rapid in vivo MRA with 129 Xe may be feasible; provided that an efficient; biologically acceptable carrier for Xe can be found and polarization levels of more than 25% can be achieved in isotopically enriched 129 Xe

Change of heavy metal speciation, mobility, bioavailability, and ecological risk during potassium ferrate treatment of waste-activated sludge.

Science.gov (United States)

Yu, Ming; Zhang, Jian; Tian, Yu

2018-05-01

The effects of potassium ferrate treatment on the heavy metal concentrations, speciation, mobility, bioavailability, and environmental risk in waste-activated sludge (WAS) at various dosages of potassium ferrate and different treatment times were investigated. Results showed that the total concentrations of all metals (except Cd) were decreased slightly after treatment and the order of metal concentrations in WAS and treated waste-activated sludge (TWAS) was Mg > Zn > Cu > Cr > Pb > Ni > Cd. Most heavy metals in WAS remained in TWAS after potassium ferrate treatment with metal residual rates over 67.8% in TWAS. The distribution of metal speciation in WAS was affected by potassium ferrate treatment. The bioavailability and the mobility of heavy metals (except Mg) in TWAS were mitigated, compared to those in WAS. Meanwhile, the environmental risk of heavy metals (except Pb and Cu) was alleviated after potassium ferrate treatment.

Differential Activity of Voltage- and Ca2+-Dependent Potassium Channels in Leukemic T Cell Lines: Jurkat Cells Represent an Exceptional Case

Directory of Open Access Journals (Sweden)

Salvador Valle-Reyes

2018-05-01

Full Text Available Activation of resting T cells relies on sustained Ca2+ influx across the plasma membrane, which in turn depends on the functional expression of potassium channels, whose activity repolarizes the membrane potential. Depending on the T-cells subset, upon activation the expression of Ca2+- or voltage-activated K+ channels, KCa or Kv, is up-regulated. In this study, by means of patch-clamp technique in the whole cell mode, we have studied in detail the characteristics of Kv and KCa currents in resting and activated human T cells, the only well explored human T-leukemic cell line Jurkat, and two additional human leukemic T cell lines, CEM and MOLT-3. Voltage dependence of activation and inactivation of Kv1.3 current were shifted up to by 15 mV to more negative potentials upon a prolonged incubation in the whole cell mode and displayed little difference at a stable state in all cell lines but CEM, where the activation curve was biphasic, with a high and low potential components. In Jurkat, KCa currents were dominated by apamine-sensitive KCa2.2 channels, whereas only KCa3.1 current was detected in healthy T and leukemic CEM and MOLT-3 cells. Despite a high proliferation potential of Jurkat cells, Kv and KCa currents were unexpectedly small, more than 10-fold lesser as compared to activated healthy human T cells, CEM and MOLT-3, which displayed characteristic Kv1.3high:KCa3.1high phenotype. Our results suggest that Jurkat cells represent perhaps a singular case and call for more extensive studies on primary leukemic T cell lines as well as a verification of the therapeutic potential of specific KCa3.1 blockers to combat acute lymphoblastic T leukemias.

Genealogical series method. Hyperpolar points screen effect

International Nuclear Information System (INIS)

Gorbatov, A.M.

1991-01-01

The fundamental values of the genealogical series method -the genealogical integrals (sandwiches) have been investigated. The hyperpolar points screen effect has been found. It allows one to calculate the sandwiches for the Fermion systems with large number of particles and to ascertain the validity of the iterated-potential method as well. For the first time the genealogical-series method has been realized numerically for the central spin-independent potential

Apparent rate constant mapping using hyperpolarized [1-(13) C]pyruvate

DEFF Research Database (Denmark)

Khegai, O.; Schulte, R. F.; Janich, M. A.

2014-01-01

Hyperpolarization of [1-13C]pyruvate in solution allows real-time measurement of uptake and metabolism using MR spectroscopic methods. After injection and perfusion, pyruvate is taken up by the cells and enzymatically metabolized into downstream metabolites such as lactate, alanine, and bicarbona...

Studies to enhance the hyperpolarization level in PHIP-SAH-produced C13-pyruvate

Science.gov (United States)

Cavallari, Eleonora; Carrera, Carla; Aime, Silvio; Reineri, Francesca

2018-04-01

The use of [1-13C]pyruvate, hyperpolarized by dissolution-Dynamic Nuclear Polarization (d-DNP), in in vivo metabolic studies has developed quickly, thanks to the imaging probe's diagnostic relevance. Nevertheless, the cost of a d-DNP polarizer is quite high and the speed of hyperpolarization process is relatively slow, meaning that its use is limited to few research laboratories. ParaHydrogen Induced Polarization Side Arm Hydrogenation (PHIP-SAH) (Reineri et al., 2015) is a cost effective and easy-to-handle method that produces 13C-MR hyperpolarization in [1-13C]pyruvate and other metabolites. This work aims to identify the main determinants of the hyperpolarization levels observed in C13-pyruvate using this method. By dissecting the various steps of the PHIP-SAH procedure, it has been possible to assess the role of several experimental parameters whose optimization must be pursued if this method is to be made suitable for future translational steps. The search for possible solutions has led to improvements in the polarization of sodium [1-13C]pyruvate from 2% to 5%. Moreover, these results suggest that observed polarization levels could be increased considerably by an automatized procedure which would reduce the time required for the work-up passages that are currently carried out manually. The results reported herein mean that the attainment of polarization levels suitable for the metabolic imaging applications of these hyperpolarized substrates show significant promise.

Regulation of renal Na+-K-ATPase in the rat: role of increased potassium transport

International Nuclear Information System (INIS)

Mujais, S.K.; Chekal, M.A.; Hayslett, J.P.; Katz, A.I.

1986-01-01

The purpose of this study was to characterize the alterations in collecting tubule Na + -K + -ATPase activity produced by sustained increments in dietary potassium in the rat and to evaluate the role of aldosterone in their generation. In adrenal-intact animals, feeding a high-potassium diet or administration of a high physiological dose of aldosterone, which simulates the delivery rate of this hormone during potassium loading, caused marked increments in Na + -K + -ATPase activity in the cortical collecting tubule (CCT) but had no effect on the enzyme in the inner stripe of the medullary collecting tubule (MCT). A significant increase in enzyme activity was also observed after smaller dietary potassium increments and after 4 days of dietary potassium load. In adrenalectomized rats provided with physiological replacement doses of corticosterone and aldosterone, Na + -K + -ATPase activity in both CCT and MCT was similar to that of adrenal-intact controls but remained unchanged after 7 days on the potassium-enriched (10-fold) diet. In contrast, adrenalectomized animals receiving the high physiological dose of aldosterone displayed an increase in Na + -K + -ATPase activity of CCT comparable with that of adrenal-intact animals, whereas the enzyme activity in the MCT was unaffected. In conclusion, 1) following chronic potassium loading Na + -K + -ATPase activity increases significantly in the CCT with no change in its activity in the inner stripe of the MCT; 2) this increase in enzyme activity occurs in a time-dependent fashion and in proportion to the potassium load; and 3) the stimulation of Na + -K + -ATPase activity in adrenal-replaced rats is facilitated by augmented levels of aldosterone, such as those actually observed in adrenal-intact rats subjected to chronic potassium loading

Regulation of renal Na -K-ATPase in the rat: role of increased potassium transport

Energy Technology Data Exchange (ETDEWEB)

Mujais, S.K.; Chekal, M.A.; Hayslett, J.P.; Katz, A.I.

1986-08-01

The purpose of this study was to characterize the alterations in collecting tubule Na -K -ATPase activity produced by sustained increments in dietary potassium in the rat and to evaluate the role of aldosterone in their generation. In adrenal-intact animals, feeding a high-potassium diet or administration of a high physiological dose of aldosterone, which simulates the delivery rate of this hormone during potassium loading, caused marked increments in Na -K -ATPase activity in the cortical collecting tubule (CCT) but had no effect on the enzyme in the inner stripe of the medullary collecting tubule (MCT). A significant increase in enzyme activity was also observed after smaller dietary potassium increments and after 4 days of dietary potassium load. In adrenalectomized rats provided with physiological replacement doses of corticosterone and aldosterone, Na -K -ATPase activity in both CCT and MCT was similar to that of adrenal-intact controls but remained unchanged after 7 days on the potassium-enriched (10-fold) diet. In contrast, adrenalectomized animals receiving the high physiological dose of aldosterone displayed an increase in Na -K -ATPase activity of CCT comparable with that of adrenal-intact animals, whereas the enzyme activity in the MCT was unaffected. In conclusion, 1) following chronic potassium loading Na -K -ATPase activity increases significantly in the CCT with no change in its activity in the inner stripe of the MCT; 2) this increase in enzyme activity occurs in a time-dependent fashion and in proportion to the potassium load; and 3) the stimulation of Na -K -ATPase activity in adrenal-replaced rats is facilitated by augmented levels of aldosterone, such as those actually observed in adrenal-intact rats subjected to chronic potassium loading.

Adsorption of triton X100 and potassium hydrogen phthalate on granular activated carbon from date pits

Energy Technology Data Exchange (ETDEWEB)

Merzougui, Z.; Nedjah, S.; Azoudj, Y.; Addoun, F. [Laboratoire d' etude physic-chimique des materiaux et application a l' environnement, Faculte de Chimie, USTHB (Algeria)], E-mail: zmerzougi@yahoo.fr

2011-07-01

Activated carbons, thanks to their versatility, are being used in the water treatment sector to absorb pollutants. Several factors influence the adsorption capacity of activated carbon and the aim of this study was to assess the effects of the porous texture and chemical nature of activated carbons on the adsorption of triton X100 and potassium hydrogen phthalate. Activated carbons used in this study were prepared from date pits with ZnCl2, KOH and H3PO4 by carbonization without adjuvant and adsorption of triton X100 and potassium hydrogen phthalate was conducted at 298K. Results showed that activated carbons prepared from date pits have a great potential for removing organic and inorganic pollutants from water and that the adsorption potential depends on the degree of activation of the activated carbons and on the compounds to absorb. This study highlighted that an increase of the carbon surface area and porosity results in a better adsorption capacity.

Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate

Science.gov (United States)

Nelson, Sarah J.; Kurhanewicz, John; Vigneron, Daniel B.; Larson, Peder E. Z.; Harzstark, Andrea L.; Ferrone, Marcus; van Criekinge, Mark; Chang, Jose W.; Bok, Robert; Park, Ilwoo; Reed, Galen; Carvajal, Lucas; Small, Eric J.; Munster, Pamela; Weinberg, Vivian K.; Ardenkjaer-Larsen, Jan Henrik; Chen, Albert P.; Hurd, Ralph E.; Odegardstuen, Liv-Ingrid; Robb, Fraser J.; Tropp, James; Murray, Jonathan A.

2014-01-01

This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo 13C MR data, it is possible to evaluate the distribution of agents such as [1-13C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-13C]lactate in tumor, with the ratio of [1-13C]lactate/[1-13C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect 13C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-13C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-13C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-13C]lactate/[1-13C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials. PMID:23946197

Regulation of potassium dependent ATPase (kdp) operon of Deinococcus radiodurans.

Science.gov (United States)

Dani, Pratiksha; Ujaoney, Aman Kumar; Apte, Shree Kumar; Basu, Bhakti

2017-01-01

The genome of D. radiodurans harbors genes for structural and regulatory proteins of Kdp ATPase, in an operon pattern, on Mega plasmid 1. Organization of its two-component regulatory genes is unique. Here we demonstrate that both, the structural as well as regulatory components of the kdp operon of D. radiodurans are expressed quickly as the cells experience potassium limitation but are not expressed upon increase in osmolarity. The cognate DNA binding response regulator (RR) effects the expression of kdp operon during potassium deficiency through specific interaction with the kdp promoter. Deletion of the gene encoding RR protein renders the mutant D. radiodurans (ΔRR) unable to express kdp operon under potassium limitation. The ΔRR D. radiodurans displays no growth defect when grown on rich media or when exposed to oxidative or heat stress but shows reduced growth following gamma irradiation. The study elucidates the functional and regulatory aspects of the novel kdp operon of this extremophile, for the first time.

A new pH-sensitive rectifying potassium channel in mitochondria from the embryonic rat hippocampus.

Science.gov (United States)

Kajma, Anna; Szewczyk, Adam

2012-10-01

Patch-clamp single-channel studies on mitochondria isolated from embryonic rat hippocampus revealed the presence of two different potassium ion channels: a large-conductance (288±4pS) calcium-activated potassium channel and second potassium channel with outwardly rectifying activity under symmetric conditions (150/150mM KCl). At positive voltages, this channel displayed a conductance of 67.84pS and a strong voltage dependence at holding potentials from -80mV to +80mV. The open probability was higher at positive than at negative voltages. Patch-clamp studies at the mitoplast-attached mode showed that the channel was not sensitive to activators and inhibitors of mitochondrial potassium channels but was regulated by pH. Moreover, we demonstrated that the channel activity was not affected by the application of lidocaine, an inhibitor of two-pore domain potassium channels, or by tertiapin, an inhibitor of inwardly rectifying potassium channels. In summary, based on the single-channel recordings, we characterised for the first time mitochondrial pH-sensitive ion channel that is selective for cations, permeable to potassium ions, displays voltage sensitivity and does not correspond to any previously described potassium ion channels in the inner mitochondrial membrane. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). Copyright © 2012 Elsevier B.V. All rights reserved.

Confirming a Role for α9nAChRs and SK Potassium Channels in Type II Hair Cells of the Turtle Posterior Crista

Directory of Open Access Journals (Sweden)

Xiaorong Xu Parks

2017-11-01

Full Text Available In turtle posterior cristae, cholinergic vestibular efferent neurons (VENs synapse on type II hair cells, bouton afferents innervating type II hair cells, and afferent calyces innervating type I hair cells. Electrical stimulation of VENs releases acetylcholine (ACh at these synapses to exert diverse effects on afferent background discharge including rapid inhibition of bouton afferents and excitation of calyx-bearing afferents. Efferent-mediated inhibition is most pronounced in bouton afferents innervating type II hair cells near the torus, but becomes progressively smaller and briefer when moving longitudinally through the crista toward afferents innervating the planum. Sharp-electrode recordings have inferred that efferent-mediated inhibition of bouton afferents requires the sequential activation of alpha9-containing nicotinic ACh receptors (α9*nAChRs and small-conductance, calcium-dependent potassium channels (SK in type II hair cells. Gradations in the strength of efferent-mediated inhibition across the crista likely reflect variations in α9*nAChRs and/or SK activation in type II hair cells from those different regions. However, in turtle cristae, neither inference has been confirmed with direct recordings from type II hair cells. To address these gaps, we performed whole-cell, patch-clamp recordings from type II hair cells within a split-epithelial preparation of the turtle posterior crista. Here, we can easily visualize and record hair cells while maintaining their native location within the neuroepithelium. Consistent with α9*nAChR/SK activation, ACh-sensitive currents in type II hair cells were inward at hyperpolarizing potentials but reversed near −90 mV to produce outward currents that typically peaked around −20 mV. ACh-sensitive currents were largest in torus hair cells but absent from hair cells near the planum. In current clamp recordings under zero-current conditions, ACh robustly hyperpolarized type II hair cells. ACh

Interactions between bicarbonate, potassium, and magnesium, and sulfur-dependent induction of luminescence in Vibrio fischeri.

Science.gov (United States)

Tabei, Yosuke; Era, Mariko; Ogawa, Akane; Morita, Hiroshi

2012-06-01

In spite of its central importance in research efforts, the relationship between seawater compounds and bacterial luminescence has not previously been investigated in detail. Thus, in this study, we investigated the effect of cations (Na(+) , K(+) , NH(4) (+) , Mg(2+) , and Ca(2+) ) and anions (Cl(-) , HCO(3) (-) , CO(3) (2-) , and NO(3) (-) ) on the induction of both inorganic (sulfate, sulfite, and thiosulfate) and organic (L-cysteine and L-cystine) sulfur-dependent luminescence in Vibrio fischeri. We found that HCO(3) (-) (bicarbonate) and CO(3) (2-) (carbonate), in the form of various compounds, had a stimulatory effect on sulfur-dependent luminescence. The luminescence induced by bicarbonate was further promoted by the addition of magnesium. Potassium also increased sulfur-dependent luminescence when sulfate or thiosulfate was supplied as the sole sulfur source, but not when sulfite, L-cysteine, or L-cystine was supplied. The positive effect of potassium was accelerated by the addition of magnesium and/or calcium. Furthermore, the additional supply of magnesium improved the induction of sulfite- or L-cysteine-dependent luminescence, but not the l-cystine-dependent type. These results suggest that sulfur-dependent luminescence of V. fischeri under nutrient-starved conditions is mainly controlled by bicarbonate, carbonate, and potassium. In addition, our results indicate that an additional supply of magnesium is effective for increasing V. fischeri luminescence. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

BK channel activators and their therapeutic perspectives

DEFF Research Database (Denmark)

Bentzen, Bo Hjorth; Olesen, Søren-Peter; Rønn, Lars C B

2014-01-01

in intracellular calcium to outward hyperpolarizing potassium currents. Consequently, the channel has many important physiological roles including regulation of smooth muscle tone, neurotransmitter release and neuronal excitability. Additionally, cardioprotective roles have been revealed in recent years. After...

Enhancing the [13C]bicarbonate signal in cardiac hyperpolarized [1‐13C]pyruvate MRS studies by infusion of glucose, insulin and potassium

DEFF Research Database (Denmark)

Lauritzen, Mette Hauge; Laustsen, Christoffer; Butt, Sadia Asghar

2013-01-01

A change in myocardial metabolism is a known effect of several diseases. MRS with hyperpolarized 13C‐labelled pyruvate is a technique capable of detecting changes in myocardial pyruvate metabolism, and has proven to be useful for the evaluation of myocardial ischaemia in vivo. However, during fas...

Slick (Kcnt2 Sodium-Activated Potassium Channels Limit Peptidergic Nociceptor Excitability and Hyperalgesia

Directory of Open Access Journals (Sweden)

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.

Molecular MRI based on hyper-polarized xenon

International Nuclear Information System (INIS)

Tassali, Nawal

2012-01-01

Magnetic Resonance Imaging (MRI) has a high importance in medicine as it enables the observation of the organs inside the body without the use of radiative or invasive techniques. However it is known to suffer from poor sensitivity. To circumvent this limitation, a key solution resides in the use of hyper-polarized species. Among the entities with which we can drastically increase nuclear polarization, xenon has very specific properties through its interactions with its close environment that lead to a wide chemical shift bandwidth. The goal is thus to use it as a tracer. This PhD thesis focuses on the concept of 129 Xe MRI-based sensors for the detection of biological events. In this approach, hyper-polarized xenon is vectorized to biological targets via functionalized host systems, and then localized thanks to fast dedicated MRI sequences. The conception and set-up of a spin-exchange optical pumping device is first described. Then studies about the interaction of the hyper-polarized noble gas with new cryptophanes susceptible to constitute powerful host molecules are detailed. Also the implementation of recent MRI sequences optimized for the transient character of the hyper-polarization and taking profit of the xenon in-out exchange is described. Applications of this approach for the detection of metallic ions and cellular receptors are studied. Finally, our first in vivo results on a small animal model are presented. (author) [fr

From retinal waves to activity-dependent retinogeniculate map development.

Science.gov (United States)

Markowitz, Jeffrey; Cao, Yongqiang; Grossberg, Stephen

2012-01-01

A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+)-activated K(+) channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.

Hyperpolarized singlet NMR on a small animal imaging system

DEFF Research Database (Denmark)

Laustsen, Christoffer; Pileio, Giuseppe; Tayler, Michael C. D.

2012-01-01

Nuclear spin hyperpolarization makes a significant advance toward overcoming the sensitivity limitations of in vivo magnetic resonance imaging, particularly in the case of low-gamma nuclei. The sensitivity may be improved further by storing the hyperpolarization in slowly relaxing singlet...... populations of spin- 1/2 pairs. Here, we report hyperpolarized 13C spin order transferred into and retrieved from singlet spin order using a small animal magnetic resonance imaging scanner. For spins in sites with very similar chemical shifts, singlet spin order is sustained in high magnetic field without...... requiring strong radiofrequency irradiation. The demonstration of robust singlet-to-magnetization conversion, and vice versa, on a small animal scanner, is promising for future in vivo and clinical deployments....

Hyperpolarized 89Y NMR spectroscopic detection of yttrium ion and DOTA macrocyclic ligand complexation: pH dependence and Y-DOTA intermediates

Science.gov (United States)

Ferguson, Sarah; Kiswandhi, Andhika; Niedbalski, Peter; Parish, Christopher; Kovacs, Zoltan; Lumata, Lloyd

Dissolution dynamic nuclear polarization (DNP) is a rapidly emerging physics technique used to enhance the signal strength in nuclear magnetic resonance (NMR) and imaging (MRI) experiments for nuclear spins such as yttrium-89 by >10,000-fold. One of the most common and stable MRI contrast agents used in the clinic is Gd-DOTA. In this work, we have investigated the binding of the yttrium and DOTA ligand as a model for complexation of Gd ion and DOTA ligand. The macrocyclic ligand DOTA is special because its complexation with lanthanide ions such as Gd3+ or Y3+ is highly pH dependent. Using this physics technology, we have tracked the complexation kinetics of hyperpolarized Y-triflate and DOTA ligand in real-time and detected the Y-DOTA intermediates. Different kinds of buffers were used (lactate, acetate, citrate, oxalate) and the pseudo-first order complexation kinetic calculations will be discussed. The authors would like to acknowledge the support by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

Effects of pulmonary inhalation on hyperpolarized krypton-83 magnetic resonance T1 relaxation.

Science.gov (United States)

Stupic, K F; Elkins, N D; Pavlovskaya, G E; Repine, J E; Meersmann, T

2011-07-07

The (83)Kr magnetic resonance (MR) relaxation time T(1) of krypton gas in contact with model surfaces was previously found to be highly sensitive to surface composition, surface-to-volume ratio, and surface temperature. The work presented here explored aspects of pulmonary (83)Kr T(1) relaxation measurements in excised lungs from healthy rats using hyperpolarized (hp) (83)Kr with approximately 4.4% spin polarization. MR spectroscopy without spatial resolution was applied to the ex vivo lungs that actively inhale hp (83)Kr through a custom designed ventilation system. Various inhalation schemes were devised to study the influence of anatomical dead space upon the measured (83)Kr T(1) relaxation times. The longitudinal (83)Kr relaxation times in the distal airways and the respiratory zones were independent of the lung inhalation volume, with T(1) = 1.3 s and T(1) = 1.0 s, depending only on the applied inhalation scheme. The obtained data were highly reproducible between different specimens. Further, the (83)Kr T(1) relaxation times in excised lungs were unaffected by the presence of up to 40% oxygen in the hp gas mixture. The results support the possible importance of (83)Kr as a biomarker for evaluating lung function.

Maternal nutrient restriction during pregnancy impairs an endothelium-derived hyperpolarizing factor-like pathway in sheep fetal coronary arteries.

Science.gov (United States)

Shukla, Praveen; Ghatta, Srinivas; Dubey, Nidhi; Lemley, Caleb O; Johnson, Mary Lynn; Modgil, Amit; Vonnahme, Kimberly; Caton, Joel S; Reynolds, Lawrence P; Sun, Chengwen; O'Rourke, Stephen T

2014-07-15

The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway. Copyright © 2014 the American Physiological Society.

The role of level anti-crossings in nuclear spin hyperpolarization

NARCIS (Netherlands)

Ivanov, Konstantin L.; Pravdivtsev, Andrey N.; Yurkovskaya, Alexandra V.; Vieth, Hans Martin; Kaptein, R

2014-01-01

Nuclear spin hyperpolarization is an important resource for increasing the sensitivity of NMR spectroscopy and MRI. Signal enhancements can be as large as 3-4 orders of magnitude. In hyperpolarization experiments, it is often desirable to transfer the initial polarization to other nuclei of choice,

Magnetic Resonance Angiography in the Pig using Hyperpolarized Water

DEFF Research Database (Denmark)

Lipsø, Hans Kasper Wigh; Bowen, Sean; Laustsen, Christoffer

, the magnetization achievable with hyperpolarized water is superior to other nuclei. Methods A 1 mL sample of 50% water and 50% glycerol with 30 mM TEMPO is polarized in a Spinlab (GE Healthcare) at 5 T, 0.9 K, 139.9 GHz for an hour. The sample is rapidly dissolved in 16 mL deoxygenized dissolution medium (DM......Introduction Magnetic Resonance Angiography (MRA) is an important tool in diagnostics of medical conditions such as emboli, stenosis and aneurysms. Sub-millimetre resolution can be obtained with proton imaging, and further optimization can be obtained with Gd-based blood pool agents1. However......, the acquisition time is several minutes, and conventional MRA methods thus fail to image within a single respiration or heartbeat and therefore suffers from motion artefacts. We demonstrate that hyperpolarized (HP) water can be used as an imaging agent to provide subsecond angiographies in pigs. Previous work...

Mutagenesis in mammalian cells can be modulated by radiation-induced voltage-dependent potassium channels

International Nuclear Information System (INIS)

Saad, A.H.; Zhou, L.Y.; Lambe, E.K.; Hahn, G.M.

1994-01-01

In mammalian cells, little is known about the initial events whose ultimate consequence is mutagenesis or DNA repair. The role the plasma membrane may play as an initiator of such a pathway is not understood. We show, for the first time, that membrane voltage-dependent potassium (K + ) currents, activated by ionizing radiation play a significant role in radiation mutagenesis. Specifically, we show that the frequency of mutation at the HGPRT locus is increased as expected to 37.6±4.0 mutations per 100,000 survivors by 800 cGy of ionizing radiation from a spontaneous frequency of 1.5±1.5. This increase, however, is abolished if either K + channel blocker, CsCl or BaCl 2 , is present for 2h following irradiation of the cells. RbCl, chemically similar to CsCl but known not to block K + channels, is ineffective in reducing the mutation frequency. Treatment of cells with CsCl or BaCl 2 had no effect on radiation-induced cell killing

Plasma-membrane hyperpolarization diminishes the cation efflux via Nha1 antiporter and Ena ATPase under potassium-limiting conditions

Czech Academy of Sciences Publication Activity Database

Zahrádka, Jaromír; Sychrová, Hana

2012-01-01

Roč. 12, č. 4 (2012), s. 439-446 ISSN 1567-1356 R&D Projects: GA MŠk(CZ) LC531; GA AV ČR(CZ) IAA500110801 Grant - others:Univerzita Karlova(CZ) 33779266 Institutional research plan: CEZ:AV0Z50110509 Keywords : potassium uptake * potassium efflux * yeast * plasma-membrane potential Subject RIV: EE - Microbiology, Virology Impact factor: 2.462, year: 2012

Optical hyperpolarization of 13C nuclear spins in nanodiamond ensembles

Science.gov (United States)

Chen, Q.; Schwarz, I.; Jelezko, F.; Retzker, A.; Plenio, M. B.

2015-11-01

Dynamical nuclear polarization holds the key for orders of magnitude enhancements of nuclear magnetic resonance signals which, in turn, would enable a wide range of novel applications in biomedical sciences. However, current implementations of DNP require cryogenic temperatures and long times for achieving high polarization. Here we propose and analyze in detail protocols that can achieve rapid hyperpolarization of 13C nuclear spins in randomly oriented ensembles of nanodiamonds at room temperature. Our protocols exploit a combination of optical polarization of electron spins in nitrogen-vacancy centers and the transfer of this polarization to 13C nuclei by means of microwave control to overcome the severe challenges that are posed by the random orientation of the nanodiamonds and their nitrogen-vacancy centers. Specifically, these random orientations result in exceedingly large energy variations of the electron spin levels that render the polarization and coherent control of the nitrogen-vacancy center electron spins as well as the control of their coherent interaction with the surrounding 13C nuclear spins highly inefficient. We address these challenges by a combination of an off-resonant microwave double resonance scheme in conjunction with a realization of the integrated solid effect which, together with adiabatic rotations of external magnetic fields or rotations of nanodiamonds, leads to a protocol that achieves high levels of hyperpolarization of the entire nuclear-spin bath in a randomly oriented ensemble of nanodiamonds even at room temperature. This hyperpolarization together with the long nuclear-spin polarization lifetimes in nanodiamonds and the relatively high density of 13C nuclei has the potential to result in a major signal enhancement in 13C nuclear magnetic resonance imaging and suggests functionalized and hyperpolarized nanodiamonds as a unique probe for molecular imaging both in vitro and in vivo.

From retinal waves to activity-dependent retinogeniculate map development.

Directory of Open Access Journals (Sweden)

Jeffrey Markowitz

Full Text Available A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+-activated K(+ channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.

Hyperpolarization-activated inward leakage currents caused by deletion or mutation of carboxy-terminal tyrosines of the Na+/K+-ATPase {alpha} subunit.

Science.gov (United States)

Meier, Susan; Tavraz, Neslihan N; Dürr, Katharina L; Friedrich, Thomas

2010-02-01

The Na(+)/K(+)-ATPase mediates electrogenic transport by exporting three Na(+) ions in exchange for two K(+) ions across the cell membrane per adenosine triphosphate molecule. The location of two Rb(+) ions in the crystal structures of the Na(+)/K(+)-ATPase has defined two "common" cation binding sites, I and II, which accommodate Na(+) or K(+) ions during transport. The configuration of site III is still unknown, but the crystal structure has suggested a critical role of the carboxy-terminal KETYY motif for the formation of this "unique" Na(+) binding site. Our two-electrode voltage clamp experiments on Xenopus oocytes show that deletion of two tyrosines at the carboxy terminus of the human Na(+)/K(+)-ATPase alpha(2) subunit decreases the affinity for extracellular and intracellular Na(+), in agreement with previous biochemical studies. Apparently, the DeltaYY deletion changes Na(+) affinity at site III but leaves the common sites unaffected, whereas the more extensive DeltaKETYY deletion affects the unique site and the common sites as well. In the absence of extracellular K(+), the DeltaYY construct mediated ouabain-sensitive, hyperpolarization-activated inward currents, which were Na(+) dependent and increased with acidification. Furthermore, the voltage dependence of rate constants from transient currents under Na(+)/Na(+) exchange conditions was reversed, and the amounts of charge transported upon voltage pulses from a certain holding potential to hyperpolarizing potentials and back were unequal. These findings are incompatible with a reversible and exclusively extracellular Na(+) release/binding mechanism. In analogy to the mechanism proposed for the H(+) leak currents of the wild-type Na(+)/K(+)-ATPase, we suggest that the DeltaYY deletion lowers the energy barrier for the intracellular Na(+) occlusion reaction, thus destabilizing the Na(+)-occluded state and enabling inward leak currents. The leakage currents are prevented by aromatic amino acids at the

Reaction monitoring using hyperpolarized NMR with scaling of heteronuclear couplings by optimal tracking

Science.gov (United States)

Zhang, Guannan; Schilling, Franz; Glaser, Steffen J.; Hilty, Christian

2016-11-01

Off-resonance decoupling using the method of Scaling of Heteronuclear Couplings by Optimal Tracking (SHOT) enables determination of heteronuclear correlations of chemical shifts in single scan NMR spectra. Through modulation of J-coupling evolution by shaped radio frequency pulses, off resonance decoupling using SHOT pulses causes a user-defined dependence of the observed J-splitting, such as the splitting of 13C peaks, on the chemical shift offset of coupled nuclei, such as 1H. Because a decoupling experiment requires only a single scan, this method is suitable for characterizing on-going chemical reactions using hyperpolarization by dissolution dynamic nuclear polarization (D-DNP). We demonstrate the calculation of [13C, 1H] chemical shift correlations of the carbanionic active sites from hyperpolarized styrene polymerized using sodium naphthalene as an initiator. While off resonance decoupling by SHOT pulses does not enhance the resolution in the same way as a 2D NMR spectrum would, the ability to obtain the correlations in single scans makes this method ideal for determination of chemical shifts in on-going reactions on the second time scale. In addition, we present a novel SHOT pulse that allows to scale J-splittings 50% larger than the respective J-coupling constant. This feature can be used to enhance the resolution of the indirectly detected chemical shift and reduce peak overlap, as demonstrated in a model reaction between p-anisaldehyde and isobutylamine. For both pulses, the accuracy is evaluated under changing signal-to-noise ratios (SNR) of the peaks from reactants and reaction products, with an overall standard deviation of chemical shift differences compared to reference spectra of 0.02 ppm when measured on a 400 MHz NMR spectrometer. Notably, the appearance of decoupling side-bands, which scale with peak intensity, appears to be of secondary importance.

Mechanism of HERG potassium channel inhibition by tetra-n-octylammonium bromide and benzethonium chloride

International Nuclear Information System (INIS)

Long, Yan; Lin, Zuoxian; Xia, Menghang; Zheng, Wei; Li, Zhiyuan

2013-01-01

Tetra-n-octylammonium bromide and benzethonium chloride are synthetic quaternary ammonium salts that are widely used in hospitals and industries for the disinfection and surface treatment and as the preservative agent. Recently, the activities of HERG channel inhibition by these compounds have been found to have potential risks to induce the long QT syndrome and cardiac arrhythmia, although the mechanism of action is still elusive. This study was conducted to investigate the mechanism of HERG channel inhibition by these compounds by using whole-cell patch clamp experiments in a CHO cell line stably expressing HERG channels. Tetra-n-octylammonium bromide and benzethonium chloride exhibited concentration-dependent inhibitions of HERG channel currents with IC 50 values of 4 nM and 17 nM, respectively, which were also voltage-dependent and use-dependent. Both compounds shifted the channel activation I–V curves in a hyperpolarized direction for 10–15 mV and accelerated channel activation and inactivation processes by 2-fold. In addition, tetra-n-octylammonium bromide shifted the inactivation I–V curve in a hyperpolarized direction for 24.4 mV and slowed the rate of channel deactivation by 2-fold, whereas benzethonium chloride did not. The results indicate that tetra-n-octylammonium bromide and benzethonium chloride are open-channel blockers that inhibit HERG channels in the voltage-dependent, use-dependent and state-dependent manners. - Highlights: ► Tetra-n-octylammonium and benzethonium are potent HERG channel inhibitors. ► Channel activation and inactivation processes are accelerated by the two compounds. ► Both compounds are the open-channel blockers to HERG channels. ► HERG channel inhibition by both compounds is use-, voltage- and state dependent. ► The in vivo risk of QT prolongation needs to be studied for the two compounds

Mechanism of HERG potassium channel inhibition by tetra-n-octylammonium bromide and benzethonium chloride

Energy Technology Data Exchange (ETDEWEB)

Long, Yan; Lin, Zuoxian [Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530 (China); Xia, Menghang; Zheng, Wei [National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Zhiyuan, E-mail: li_zhiyuan@gibh.ac.cn [Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530 (China)

2013-03-01

Tetra-n-octylammonium bromide and benzethonium chloride are synthetic quaternary ammonium salts that are widely used in hospitals and industries for the disinfection and surface treatment and as the preservative agent. Recently, the activities of HERG channel inhibition by these compounds have been found to have potential risks to induce the long QT syndrome and cardiac arrhythmia, although the mechanism of action is still elusive. This study was conducted to investigate the mechanism of HERG channel inhibition by these compounds by using whole-cell patch clamp experiments in a CHO cell line stably expressing HERG channels. Tetra-n-octylammonium bromide and benzethonium chloride exhibited concentration-dependent inhibitions of HERG channel currents with IC{sub 50} values of 4 nM and 17 nM, respectively, which were also voltage-dependent and use-dependent. Both compounds shifted the channel activation I–V curves in a hyperpolarized direction for 10–15 mV and accelerated channel activation and inactivation processes by 2-fold. In addition, tetra-n-octylammonium bromide shifted the inactivation I–V curve in a hyperpolarized direction for 24.4 mV and slowed the rate of channel deactivation by 2-fold, whereas benzethonium chloride did not. The results indicate that tetra-n-octylammonium bromide and benzethonium chloride are open-channel blockers that inhibit HERG channels in the voltage-dependent, use-dependent and state-dependent manners. - Highlights: ► Tetra-n-octylammonium and benzethonium are potent HERG channel inhibitors. ► Channel activation and inactivation processes are accelerated by the two compounds. ► Both compounds are the open-channel blockers to HERG channels. ► HERG channel inhibition by both compounds is use-, voltage- and state dependent. ► The in vivo risk of QT prolongation needs to be studied for the two compounds.

Hyperpolarized krypton-83 as a contrast agent for magnetic resonance imaging.

Science.gov (United States)

Pavlovskaya, Galina E; Cleveland, Zackary I; Stupic, Karl F; Basaraba, Randall J; Meersmann, Thomas

2005-12-20

For the first time, magnetic resonance imaging (MRI) with hyperpolarized (hp) krypton-83 (83Kr) has become available. The relaxation of the nuclear spin of 83Kr atoms (I = 9/2) is driven by quadrupolar interactions during brief adsorption periods on surrounding material interfaces. Experiments in model systems reveal that the longitudinal relaxation of hp 83Kr gas strongly depends on the chemical composition of the materials. The relaxation-weighted contrast in hp 83Kr MRI allows for the distinction between hydrophobic and hydrophilic surfaces. The feasibility of hp 83Kr MRI of airways is tested in canine lung tissue by using krypton gas with natural abundance isotopic distribution. Additionally, the influence of magnetic field strength and the presence of a breathable concentration of molecular oxygen on longitudinal relaxation are investigated.

A catalyzing phantom for reproducible dynamic conversion of hyperpolarized [1-¹³C]-pyruvate.

Science.gov (United States)

Walker, Christopher M; Lee, Jaehyuk; Ramirez, Marc S; Schellingerhout, Dawid; Millward, Steven; Bankson, James A

2013-01-01

In vivo real time spectroscopic imaging of hyperpolarized ¹³C labeled metabolites shows substantial promise for the assessment of physiological processes that were previously inaccessible. However, reliable and reproducible methods of measurement are necessary to maximize the effectiveness of imaging biomarkers that may one day guide personalized care for diseases such as cancer. Animal models of human disease serve as poor reference standards due to the complexity, heterogeneity, and transient nature of advancing disease. In this study, we describe the reproducible conversion of hyperpolarized [1-¹³C]-pyruvate to [1-¹³C]-lactate using a novel synthetic enzyme phantom system. The rate of reaction can be controlled and tuned to mimic normal or pathologic conditions of varying degree. Variations observed in the use of this phantom compare favorably against within-group variations observed in recent animal studies. This novel phantom system provides crucial capabilities as a reference standard for the optimization, comparison, and certification of quantitative imaging strategies for hyperpolarized tracers.

A catalyzing phantom for reproducible dynamic conversion of hyperpolarized [1-¹³C]-pyruvate.

Directory of Open Access Journals (Sweden)

Christopher M Walker

Full Text Available In vivo real time spectroscopic imaging of hyperpolarized ¹³C labeled metabolites shows substantial promise for the assessment of physiological processes that were previously inaccessible. However, reliable and reproducible methods of measurement are necessary to maximize the effectiveness of imaging biomarkers that may one day guide personalized care for diseases such as cancer. Animal models of human disease serve as poor reference standards due to the complexity, heterogeneity, and transient nature of advancing disease. In this study, we describe the reproducible conversion of hyperpolarized [1-¹³C]-pyruvate to [1-¹³C]-lactate using a novel synthetic enzyme phantom system. The rate of reaction can be controlled and tuned to mimic normal or pathologic conditions of varying degree. Variations observed in the use of this phantom compare favorably against within-group variations observed in recent animal studies. This novel phantom system provides crucial capabilities as a reference standard for the optimization, comparison, and certification of quantitative imaging strategies for hyperpolarized tracers.

Commensal Bacteria-Induced Inflammasome Activation in Mouse and Human Macrophages Is Dependent on Potassium Efflux but Does Not Require Phagocytosis or Bacterial Viability.

Directory of Open Access Journals (Sweden)

Kejie Chen

Full Text Available Gut commensal bacteria contribute to the pathogenesis of inflammatory bowel disease, in part by activating the inflammasome and inducing secretion of interleukin-1ß (IL-1ß. Although much has been learned about inflammasome activation by bacterial pathogens, little is known about how commensals carry out this process. Accordingly, we investigated the mechanism of inflammasome activation by representative commensal bacteria, the Gram-positive Bifidobacterium longum subspecies infantis and the Gram-negative Bacteroides fragilis. B. infantis and B. fragilis induced IL-1ß secretion by primary mouse bone marrow-derived macrophages after overnight incubation. IL-1ß secretion also occurred in response to heat-killed bacteria and was only partly reduced when phagocytosis was inhibited with cytochalasin D. Similar results were obtained with a wild-type immortalized mouse macrophage cell line but neither B. infantis nor B. fragilis induced IL-1ß secretion in a mouse macrophage line lacking the nucleotide-binding/leucine-rich repeat pyrin domain containing 3 (NLRP3 inflammasome. IL-1ß secretion in response to B. infantis and B. fragilis was significantly reduced when the wild-type macrophage line was treated with inhibitors of potassium efflux, either increased extracellular potassium concentrations or the channel blocker ruthenium red. Both live and heat-killed B. infantis and B. fragilis also induced IL-1ß secretion by human macrophages (differentiated THP-1 cells or primary monocyte-derived macrophages after 4 hours of infection, and the secretion was inhibited by raised extracellular potassium and ruthenium red but not by cytochalasin D. Taken together, our findings indicate that the commensal bacteria B. infantis and B. fragilis activate the NLRP3 inflammasome in both mouse and human macrophages by a mechanism that involves potassium efflux and that does not require bacterial viability or phagocytosis.

Activation of endothelial and epithelial K(Ca) 2.3 calcium-activated potassium channels by NS309 relaxes human small pulmonary arteries and bronchioles

DEFF Research Database (Denmark)

Kroigaard, Christel; Dalsgaard, Thomas; Nielsen, Gorm

2012-01-01

BACKGROUND AND PURPOSE: Small (K(Ca) 2) and intermediate (K(Ca) 3.1) conductance calcium-activated potassium channels (K(Ca) ) may contribute to both epithelium- and endothelium-dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we inv...... targets for treatment of pulmonary hypertension and chronic obstructive pulmonary disease....

Transmit-Only/Receive-Only Radiofrequency System for Hyperpolarized 13C MRS Cardiac Metabolism Studies in Pigs

DEFF Research Database (Denmark)

Giovannetti, G.; Frijia, F.; Hartwig, V.

2013-01-01

Hyperpolarized 13C magnetic resonance spectroscopy in pig models enables metabolic activity mapping, providing a powerful tool for the study of the heart physiology, but requires the development of dedicated radiofrequency coils, capable of providing large field of view with high signal......-to-noise ratio (SNR) data. This work describes the simulations and the tests of a transmit-only (TX) volume coil/receive-only (RX) surface coil both designed for hyperpolarized studies of pig heart with a clinical 3T scanner. The coil characterization is performed by developing an SNR model for coil performance...

Real-time tracking of dissociation of hyperpolarized 89Y-DTPA: a model for degradation of open-chain Gd3+ MRI contrast agents

Science.gov (United States)

Ferguson, Sarah; Niedbalski, Peter; Parish, Christopher; Kiswandhi, Andhika; Kovacs, Zoltan; Lumata, Lloyd

Gadolinium (Gd) complexes are widely used relaxation-based clinical contrast agents in magnetic resonance imaging (MRI). Gd-based MRI contrast agents with open-chain ligand such as Gd-DTPA, commercially known as magnevist, are less stable compared to Gd complexes with macrocyclic ligands such as GdDOTA (Dotarem). The dissociation of Gd-DPTA into Gd ion and DTPA ligand under certain biological conditions such as high zinc levels can potentially cause kidney damage. Since Gd is paramagnetic, direct NMR detection of the Gd-DTPA dissociation is quite challenging due to ultra-short relaxation times. In this work, we have investigated Y-DTPA as a model for Gd-DPTA dissociation under high zinc content solutions. Using dissolution dynamic nuclear polarization (DNP), the 89Y NMR signal is amplified by several thousand-fold. Due to the the relatively long T1 relaxation time of 89Y which translates to hyperpolarization lifetime of several minutes, the dissociation of Y-DTPA can be tracked in real-time by hyperpolarized 89Y NMR spectroscopy. Dissociation kinetic rates and implications on the degradation of open-chain Gd3+ MRI contrast agents will be discussed. This work was supported by the U.S. Department of Defense Award Number W81XWH-14-1-0048 and by the Robert A. Welch Foundation research Grant Number AT-1877.

Monoaminergic tone supports conductance correlations and stabilizes activity features in pattern generating neurons of the lobster, Panulirus interruptus

Directory of Open Access Journals (Sweden)

Wulf-Dieter C. Krenz

2015-10-01

Full Text Available Experimental and computational studies demonstrate that different sets of intrinsic and synaptic conductances can give rise to equivalent activity patterns. This is because the balance of conductances, not their absolute values, defines a given activity feature. Activity-dependent feedback mechanisms maintain neuronal conductance correlations and their corresponding activity features. This study demonstrates that tonic nM concentrations of monoamines enable slow, activity-dependent processes that can maintain a correlation between the transient potassium current (IA and the hyperpolarization activated current (Ih over the long-term (i.e., regulatory change persists for hours after removal of modulator. Tonic 5nM DA acted through an RNA interference silencing complex (RISC- and RNA polymerase II-dependent mechanism to maintain a long-term positive correlation between IA and Ih in the lateral pyloric neuron (LP but not in the pyloric dilator neuron (PD. In contrast, tonic 5nM 5HT maintained a RISC-dependent positive correlation between IA and Ih in PD but not LP over the long-term. Tonic 5nM OCT maintained a long-term negative correlation between IA and Ih in PD but not LP; however, it was only revealed when RISC was inhibited. This study also demonstrated that monoaminergic tone can also preserve activity features over the long-term: The timing of LP activity, LP duty cycle and LP spike number per burst were maintained by tonic 5nM DA. The data suggest that low-level monoaminergic tone acts through multiple slow processes to permit cell-specific, activity-dependent regulation of ionic conductances to maintain conductance correlations and their corresponding activity features over the long-term.

Monitoring mammary tumor progression and effect of tamoxifen treatment in MMTV-PymT using MRI and magnetic resonance spectroscopy with hyperpolarized [1-¹³C]pyruvate

DEFF Research Database (Denmark)

Asghar Butt, Sadia; Søgaard, Lise V.; Ardenkjær-Larsen, Jan Henrik

2015-01-01

Purpose: To use dynamic magnetic resonance spectroscopy (MRS) of hyperpolarized 13C-pyruvate to follow the progress over time in vivo of breast cancer metabolism in the MMTV-PymT model, and to follow the response to the anti-estrogen drug tamoxifen. Methods: Tumor growth was monitored by anatomical...... significantly in the treated group. Conclusion: These hyperpolarized 13C MRS findings indicate that tumor metabolic changes affects kP. The measured kp did not relate to treatment response to the same extent as did tumor growth, histological evaluation, and in vitro determination of LDH activity. © 2014 Wiley...

A novel MR contrast agent for angiography and perfusion: Hyperpolarized water

DEFF Research Database (Denmark)

Lipsø, Hans Kasper Wigh

, hyperpolarized by dissolution Dynamic Nuclear Polarization (d-DNP), can be applied as an MRI contrast agent for angiography and perfusion. The first part of the project focuses on development of a protocol for production of large samples of hyperpolarized protons in D2O. The samples are polarized and dissolved...

Effects of haloperidol on Kv4.3 potassium channels.

Science.gov (United States)

Lee, Hong Joon; Sung, Ki-Wug; Hahn, Sang June

2014-10-05

Haloperidol is commonly used in clinical practice to treat acute and chronic psychosis, but it also has been associated with adverse cardiovascular events. We investigated the effects of haloperidol on Kv4.3 currents stably expressed in CHO cells using a whole-cell patch-clamp technique. Haloperidol did not significantly inhibit the peak amplitude of Kv4.3, but accelerated the decay rate of inactivation of Kv4.3 in a concentration-dependent manner. Thus, the effects of haloperidol on Kv4.3 were estimated from the integral of the Kv4.3 currents during the depolarization pulse. The Kv4.3 was decreased by haloperidol in a concentration-dependent manner with an IC50 value of 3.6 μM. Haloperidol accelerated the decay rate of Kv4.3 inactivation and activation kinetics in a concentration-dependent manner, thereby decreasing the time-to-peak. Haloperidol shifted the voltage dependence of the steady-state activation and inactivation of Kv4.3 in a hyperpolarizing direction. Haloperidol also caused an acceleration of the closed-state inactivation of Kv4.3. Haloperidol produced a use-dependent block of Kv4.3, which was accompanied by a slowing of recovery from the inactivation of Kv4.3. These results suggest that haloperidol blocks Kv4.3 by both interacting with the open state of Kv4.3 channels during depolarization and accelerating the closed-state inactivation at subthreshold membrane potentials. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis of long T silicon nanoparticles for hyperpolarized Si magnetic resonance imaging

DEFF Research Database (Denmark)

Atkins, T.M.; Ganguly, S.; Kauzlarich, S.M.

2013-01-01

silicide (Na Si) and silicon tetrachloride (SiCl) and were surface functionalized with a variety of passivating ligands. The synthesis scheme results in particles of diameter ~10 nm with long size-adjusted Si spin-lattice relaxation (T) times (>600 s), which are retained after hyperpolarization by low...

Extracellular Calcium-Dependent Modulation of Endothelium Relaxation in Rat Mesenteric Small Artery

DEFF Research Database (Denmark)

Hangaard, Lise; Jessen, Peter B; Kamaev, Dmitrii

2015-01-01

The nature of NO- and COX-independent endothelial hyperpolarization (EDH) is not fully understood but activation of small- and intermittent-conductance Ca(2+)-activated K(+) channels (SKCa and IKCa) is important. Previous studies have suggested that the significance of IKCa depends on [Ca(2+)]out...

Reduced resting potentials in dystrophic (mdx) muscle fibers are secondary to NF-κB-dependent negative modulation of ouabain sensitive Na+-K+ pump activity.

Science.gov (United States)

Miles, M T; Cottey, E; Cottey, A; Stefanski, C; Carlson, C G

2011-04-15

To examine potential mechanisms for the reduced resting membrane potentials (RPs) of mature dystrophic (mdx) muscle fibers, the Na(+)-K(+) pump inhibitor ouabain was added to freshly isolated nondystrophic and mdx fibers. Ouabain produced a 71% smaller depolarization in mdx fibers than in nondystrophic fibers, increased the [Na(+)](i) in nondystrophic fibers by 40%, but had no significant effect on the [Na(+)](i) of mdx fibers, which was approximately double that observed in untreated nondystrophic fibers. Western blots indicated no difference in total and phosphorylated Na(+)-K(+) ATPase catalytic α1 subunit between nondystrophic and mdx muscle. Examination of the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) indicated that direct application of the drug slowly hyperpolarized mdx fibers (7 mV in 90 min) but had no effect on nondystrophic fibers. Pretreatment with ouabain abolished this hyperpolarization, and pretreatment with PDTC restored ouabain-induced depolarization and reduced [Na(+)](i). Administration of an NF-κB inhibitor that utilizes a different mechanism for reducing nuclear NF-κB activation, ursodeoxycholic acid (UDCA), also hyperpolarized mdx fibers. These results suggest that in situ Na(+)-K(+) pump activity is depressed in mature dystrophic fibers by NF-κB dependent modulators, and that this reduced pump activity contributes to the weakness characteristic of dystrophic muscle. Copyright © 2011 Elsevier B.V. All rights reserved.

Ratiometric analysis in hyperpolarized NMR (I): test of the two-site exchange model and the quantification of reaction rate constants.

Science.gov (United States)

Li, Lin Z; Kadlececk, Stephen; Xu, He N; Daye, Dania; Pullinger, Benjamin; Profka, Harrilla; Chodosh, Lewis; Rizi, Rahim

2013-10-01

Conventional methods for the analysis of in vivo hyperpolarized (13) C NMR data from the lactate dehydrogenase (LDH) reaction usually make assumptions on the stability of rate constants and/or the validity of the two-site exchange model. In this study, we developed a framework to test the validity of the assumption of stable reaction rate constants and the two-site exchange model in vivo via ratiometric fitting of the time courses of the signal ratio L(t)/P(t). Our analysis provided evidence that the LDH enzymatic kinetics observed by hyperpolarized NMR are in near-equilibrium and satisfy the two-site exchange model for only a specific time window. In addition, we quantified both the forward and reverse exchange rate constants of the LDH reaction for the transgenic and mouse xenograft models of breast cancer using the ratio fitting method developed, which includes only two modeling parameters and is less sensitive to the influence of instrument settings/protocols, such as flip angles, degree of polarization and tracer dosage. We further compared the ratio fitting method with a conventional two-site exchange modeling method, i.e. the differential equation fitting method, using both the experimental and simulated hyperpolarized NMR data. The ratio fitting method appeared to fit better than the differential equation fitting method for the reverse rate constant on the mouse tumor data, with less relative errors on average, whereas the differential equation fitting method also resulted in a negative reverse rate constant for one tumor. The simulation results indicated that the accuracy of both methods depends on the width of the transport function, noise level and rate constant ratio; one method may be more accurate than the other based on the experimental/biological conditions aforementioned. We were able to categorize our tumor models into specific conditions of the computer simulation and to estimate the errors of rate quantification. We also discussed possible

Activation of high and low affinity dopamine receptors generates a closed loop that maintains a conductance ratio and its activity correlate

Directory of Open Access Journals (Sweden)

Wulf-Dieter Christian Krenz

2013-10-01

Full Text Available Neuromodulators alter network output and have the potential to destabilize a circuit. The mechanisms maintaining stability in the face of neuromodulation are not well described. Using the pyloric network in the crustacean stomatogastric nervous system, we show that dopamine (DA does not simply alter circuit output, but activates a closed loop in which DA-induced alterations in circuit output consequently drive a change in an ionic conductance to preserve a conductance ratio and its activity correlate. DA acted at low affinity type 1 receptors (D1Rs to induce an immediate modulatory decrease in the transient potassium current (IA of a pyloric neuron. This, in turn, advanced the activity phase of that component neuron, which disrupted its network function and thereby destabilized the circuit. DA simultaneously acted at high affinity D1Rs on the same neuron to confer activity-dependence upon the hyperpolarization activated current (Ih such that the DA-induced changes in activity subsequently reduced Ih. This DA-enabled, activity-dependent, intrinsic plasticity exactly compensated for the modulatory decrease in IA to restore the IA:Ih ratio and neuronal activity phase, thereby closing an open loop created by the modulator. Activation of closed loops to preserve conductance ratios may represent a fundamental operating principle neuromodulatory systems use to ensure stability in their target networks.

Irreversible Catalyst Activation Enables Hyperpolarization and Water Solubility for NMR Signal Amplification by Reversible Exchange

Science.gov (United States)

2016-09-12

G. R.; Duckett, S. B.; Spiess , H. W.; Schreiber, L. M.; Münnemann, K. Continuous Proton Hyperpolarization Via SABRE and Hollow Fibre Membranes. Proc...M.; Kindervater, P.; Raich, H.-P.; Bargon, J.; Spiess , H. W.; Muennemann, K. Continuous H-1 and C-13 Signal Enhancement in NMR Spectroscopy and MRI

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...

Real-Time in Vivo Detection of H2O2 Using Hyperpolarized 13C-Thiourea.

Science.gov (United States)

Wibowo, Arif; Park, Jae Mo; Liu, Shie-Chau; Khosla, Chaitan; Spielman, Daniel M

2017-07-21

Reactive oxygen species (ROS) are essential cellular metabolites widely implicated in many diseases including cancer, inflammation, and cardiovascular and neurodegenerative disorders. Yet, ROS signaling remains poorly understood, and their measurements are a challenge due to high reactivity and instability. Here, we report the development of 13 C-thiourea as a probe to detect and measure H 2 O 2 dynamics with high sensitivity and spatiotemporal resolution using hyperpolarized 13 C magnetic resonance spectroscopic imaging. In particular, we show 13 C-thiourea to be highly polarizable and to possess a long spin-lattice relaxation time (T 1 ), which enables real-time monitoring of ROS-mediated transformation. We also demonstrate that 13 C-thiourea reacts readily with H 2 O 2 to give chemically distinguishable products in vitro and validate their detection in vivo in a mouse liver. This study suggests that 13 C-thiourea is a promising agent for noninvasive detection of H 2 O 2 in vivo. More broadly, our findings outline a viable clinical application for H 2 O 2 detection in patients with a range of diseases.

Nicorandil-Induced Hyperkalemia in a Uremic Patient

Directory of Open Access Journals (Sweden)

Hung-Hao Lee

2012-01-01

Full Text Available Nicorandil is an antianginal agent with nitrate-like and ATP-sensitive potassium channel activator properties. After activation of potassium channels, potassium ions are expelled out of the cells, which lead to membrane hyperpolarization, closure of voltage-gated calcium channels, and finally vasodilation. We present a uremic case suffering from repeated junctional bradycardia, especially before hemodialysis. After detailed evaluation, nicorandil was suspected to be the cause of hyperkalemia which induced bradycardia. This case reminds us that physicians should be aware of this potential complication in patients receiving ATP-sensitive potassium channel activator.

Characterization of Chemical Exchange Using Relaxation Dispersion of Hyperpolarized Nuclear Spins.

Science.gov (United States)

Liu, Mengxiao; Kim, Yaewon; Hilty, Christian

2017-09-05

Chemical exchange phenomena are ubiquitous in macromolecules, which undergo conformational change or ligand complexation. NMR relaxation dispersion (RD) spectroscopy based on a Carr-Purcell-Meiboom-Gill pulse sequence is widely applied to identify the exchange and measure the lifetime of intermediate states on the millisecond time scale. Advances in hyperpolarization methods improve the applicability of NMR spectroscopy when rapid acquisitions or low concentrations are required, through an increase in signal strength by several orders of magnitude. Here, we demonstrate the measurement of chemical exchange from a single aliquot of a ligand hyperpolarized by dissolution dynamic nuclear polarization (D-DNP). Transverse relaxation rates are measured simultaneously at different pulsing delays by dual-channel 19 F NMR spectroscopy. This two-point measurement is shown to allow the determination of the exchange term in the relaxation rate expression. For the ligand 4-(trifluoromethyl)benzene-1-carboximidamide binding to the protein trypsin, the exchange term is found to be equal within error limits in neutral and acidic environments from D-DNP NMR spectroscopy, corresponding to a pre-equilibrium of trypsin deprotonation. This finding illustrates the capability for determination of binding mechanisms using D-DNP RD. Taking advantage of hyperpolarization, the ligand concentration in the exchange measurements can reach on the order of tens of μM and protein concentration can be below 1 μM, i.e., conditions typically accessible in drug discovery.

Properties of Single K+ and Cl− Channels in Asclepias tuberosa Protoplasts 1

Science.gov (United States)

Schauf, Charles L.; Wilson, Kathryn J.

1987-01-01

Potassium and chloride channels were characterized in Asclepias tuberosa suspension cell derived protoplasts by patch voltage-clamp. Whole-cell currents and single channels in excised patches had linear instantaneous current-voltage relations, reversing at the Nernst potentials for K+ and Cl−, respectively. Whole cell K+ currents activated exponentially during step depolarizations, while voltage-dependent Cl− channels were activated by hyperpolarizations. Single K+ channel conductance was 40 ± 5 pS with a mean open time of 4.5 milliseconds at 100 millivolts. Potassium channels were blocked by Cs+ and tetraethylammonium, but were insensitive to 4-aminopyridine. Chloride channels had a single-channel conductance of 100 ± 17 picosiemens, mean open time of 8.8 milliseconds, and were blocked by Zn2+ and ethacrynic acid. Whole-cell Cl− currents were inhibited by abscisic acid, and were unaffected by indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid. Since internal and external composition can be controlled, patch-clamped protoplasts are ideal systems for studying the role of ion channels in plant physiology and development. Images Fig. 5 PMID:16665712

The electrically silent Kv6.4 subunit confers hyperpolarized gating charge movement in Kv2.1/Kv6.4 heterotetrameric channels.

Directory of Open Access Journals (Sweden)

Elke Bocksteins

Full Text Available The voltage-gated K(+ (Kv channel subunit Kv6.4 does not form functional homotetrameric channels but co-assembles with Kv2.1 to form functional Kv2.1/Kv6.4 heterotetrameric channels. Compared to Kv2.1 homotetramers, Kv6.4 exerts a ~40 mV hyperpolarizing shift in the voltage-dependence of Kv2.1/Kv6.4 channel inactivation, without a significant effect on activation gating. However, the underlying mechanism of this Kv6.4-induced modulation of Kv2.1 channel inactivation, and whether the Kv6.4 subunit participates in the voltage-dependent gating of heterotetrameric channels is not well understood. Here we report distinct gating charge movement of Kv2.1/Kv6.4 heterotetrameric channels, compared to Kv2.1 homotetramers, as revealed by gating current recordings from mammalian cells expressing these channels. The gating charge movement of Kv2.1/Kv6.4 heterotetrameric channels displayed an extra component around the physiological K(+ equilibrium potential, characterized by a second sigmoidal relationship of the voltage-dependence of gating charge movement. This distinct gating charge displacement reflects movement of the Kv6.4 voltage-sensing domain and has a voltage-dependency that matches the hyperpolarizing shift in Kv2.1/Kv6.4 channel inactivation. These results provide a mechanistic basis for the modulation of Kv2.1 channel inactivation gating kinetics by silent Kv6.4 subunits.

Disulfide mapping the voltage-sensing mechanism of a voltage-dependent potassium channel.

Science.gov (United States)

Nozaki, Tomohiro; Ozawa, Shin-Ichiro; Harada, Hitomi; Kimura, Tomomi; Osawa, Masanori; Shimada, Ichio

2016-11-17

Voltage-dependent potassium (Kv) channels allow for the selective permeability of potassium ions in a membrane potential dependent manner, playing crucial roles in neurotransmission and muscle contraction. Kv channel is a tetramer, in which each subunit possesses a voltage-sensing domain (VSD) and a pore domain (PD). Although several lines of evidence indicated that membrane depolarization is sensed as the movement of helix S4 of the VSD, the detailed voltage-sensing mechanism remained elusive, due to the difficulty of structural analyses at resting potential. In this study, we conducted a comprehensive disulfide locking analysis of the VSD using 36 double Cys mutants, in order to identify the proximal residue pairs of the VSD in the presence or absence of a membrane potential. An intramolecular SS-bond was formed between 6 Cys pairs under both polarized and depolarized environment, and one pair only under depolarized environment. The multiple conformations captured by the SS-bond can be divided by two states, up and down, where S4 lies on the extracellular and intracellular sides of the membrane, respectively, with axial rotation of 180°. The transition between these two states is caused by the S4 translocation of 12 Å, enabling allosteric regulation of the gating at the PD.

Composition effect of potassium-borate glasses on their relaxation properties

International Nuclear Information System (INIS)

Lomovskoj, V.A.; Bartenev, G.M.

1995-01-01

Relaxation processes in potassium-borate glasses have been investigated in detail for the first time. It is shown that low-temperature β-process of relaxation relating to rotational mobility of the B-O bond is the same for all potassium-borate glasses and B 2 O 3 . The process of β k -relaxation related to diffusion mobility of potassium ions depends on the composition of the glasses in the same way as α-relaxation (glass formation).12 refs., 10 figs., 2 tabs

Hyperpolarized 3-helium MR imaging of the lungs: testing the concept of a central production facility

International Nuclear Information System (INIS)

Beek, E.J.R. van; Schmiedeskamp, J.; Filbir, F.; Heil, W.; Wolf, M.; Otten, E.; Wild, J.M.; Paley, M.N.J.; Fichele, S.; Woodhouse, N.; Swift, A.; Knitz, F.; Mills, G.H.

2003-01-01

The aim of this study was to test the feasibility of a central production facility with distribution network for implementation of hyperpolarized 3-helium MRI. The 3-helium was hyperpolarized to 50-65% using a large-scale production facility based at a university in Germany. Using a specially designed transport box, containing a permanent low-field shielded magnet and dedicated iron-free glass cells, the hyperpolarized 3-helium gas was transported via airfreight to a university in the UK. At this location, the gas was used to perform in vivo MR experiments in normal volunteers and patients with chronic obstructive lung diseases. Following initial tests, the transport (road-air-road cargo) was successfully arranged on six occasions (approximately once per month). The duration of transport to imaging averaged 18 h (range 16-20 h), which was due mainly to organizational issues such as working times and flight connections. During the course of the project, polarization at imaging increased from 20% to more than 30%. A total of 4 healthy volunteers and 8 patients with chronic obstructive pulmonary disease were imaged. The feasibility of a central production facility for hyperpolarized 3-helium was demonstrated. This should enable a wider distribution of gas for this novel technology without the need for local start-up costs. (orig.)

Homogeneous distribution of large-conductance calcium-dependent potassium channels on soma and apical dendrite of rat neocortical layer 5 pyramidal neurons.

Science.gov (United States)

Benhassine, Narimane; Berger, Thomas

2005-02-01

Voltage-gated conductances on dendrites of layer 5 pyramidal neurons participate in synaptic integration and output generation. We investigated the properties and the distribution of large-conductance calcium-activated potassium channels (BK channels) in this cell type using excised patches in acute slice preparations of rat somatosensory cortex. BK channels were characterized by their large conductance and sensitivity to the specific blockers paxilline and iberiotoxin. BK channels showed a pronounced calcium-dependence with a maximal opening probability of 0.69 at 10 microm and 0.42 at 3 microm free calcium. Their opening probability and transition time constants between open and closed states are voltage-dependent. At depolarized potentials, BK channel gating is described by two open and one closed states. Depolarization increases the opening probability due to a prolongation of the open time constant and a shortening of the closed time constant. Calcium-dependence and biophysical properties of somatic and dendritic BK channels were identical. The presence of BK channels on the apical dendrite of layer 5 pyramidal neurons was shown by immunofluorescence. Patch-clamp recordings revealed a homogeneous density of BK channels on the soma and along the apical dendrite up to 850 microm with a mean density of 1.9 channels per microm(2). BK channels are expressed either isolated or in clusters containing up to four channels. This study shows the presence of BK channels on dendrites. Their activation might modulate the shape of sodium and calcium action potentials, their propagation along the dendrite, and thereby the electrotonic distance between the somatic and dendritic action potential initiation zones.

Volumetric spiral chemical shift imaging of hyperpolarized [2-(13) c]pyruvate in a rat c6 glioma model.

Science.gov (United States)

Park, Jae Mo; Josan, Sonal; Jang, Taichang; Merchant, Milton; Watkins, Ron; Hurd, Ralph E; Recht, Lawrence D; Mayer, Dirk; Spielman, Daniel M

2016-03-01

MRS of hyperpolarized [2-(13)C]pyruvate can be used to assess multiple metabolic pathways within mitochondria as the (13)C label is not lost with the conversion of pyruvate to acetyl-CoA. This study presents the first MR spectroscopic imaging of hyperpolarized [2-(13)C]pyruvate in glioma-bearing brain. Spiral chemical shift imaging with spectrally undersampling scheme (1042 Hz) and a hard-pulse excitation was exploited to simultaneously image [2-(13)C]pyruvate, [2-(13)C]lactate, and [5-(13)C]glutamate, the metabolites known to be produced in brain after an injection of hyperpolarized [2-(13)C]pyruvate, without chemical shift displacement artifacts. A separate undersampling scheme (890 Hz) was also used to image [1-(13)C]acetyl-carnitine. Healthy and C6 glioma-implanted rat brains were imaged at baseline and after dichloroacetate administration, a drug that modulates pyruvate dehydrogenase kinase activity. The baseline metabolite maps showed higher lactate and lower glutamate in tumor as compared to normal-appearing brain. Dichloroacetate led to an increase in glutamate in both tumor and normal-appearing brain. Dichloroacetate-induced %-decrease of lactate/glutamate was comparable to the lactate/bicarbonate decrease from hyperpolarized [1-(13)C]pyruvate studies. Acetyl-carnitine was observed in the muscle/fat tissue surrounding the brain. Robust volumetric imaging with hyperpolarized [2-(13)C]pyruvate and downstream products was performed in glioma-bearing rat brains, demonstrating changes in mitochondrial metabolism with dichloroacetate. © 2015 Wiley Periodicals, Inc.

3D Hyperpolarized C-13 EPI with Calibrationless Parallel Imaging

DEFF Research Database (Denmark)

Gordon, Jeremy W.; Hansen, Rie Beck; Shin, Peter J.

2018-01-01

With the translation of metabolic MRI with hyperpolarized 13C agents into the clinic, imaging approaches will require large volumetric FOVs to support clinical applications. Parallel imaging techniques will be crucial to increasing volumetric scan coverage while minimizing RF requirements and tem...... strategies to accelerate and undersample hyperpolarized 13C data using 3D blipped EPI acquisitions and multichannel receive coils, and demonstrated its application in a human study of [1-13C]pyruvate metabolism....

Mirror Neurons Modeled Through Spike-Timing-Dependent Plasticity are Affected by Channelopathies Associated with Autism Spectrum Disorder.

Science.gov (United States)

Antunes, Gabriela; Faria da Silva, Samuel F; Simoes de Souza, Fabio M

2018-06-01

Mirror neurons fire action potentials both when the agent performs a certain behavior and watches someone performing a similar action. Here, we present an original mirror neuron model based on the spike-timing-dependent plasticity (STDP) between two morpho-electrical models of neocortical pyramidal neurons. Both neurons fired spontaneously with basal firing rate that follows a Poisson distribution, and the STDP between them was modeled by the triplet algorithm. Our simulation results demonstrated that STDP is sufficient for the rise of mirror neuron function between the pairs of neocortical neurons. This is a proof of concept that pairs of neocortical neurons associating sensory inputs to motor outputs could operate like mirror neurons. In addition, we used the mirror neuron model to investigate whether channelopathies associated with autism spectrum disorder could impair the modeled mirror function. Our simulation results showed that impaired hyperpolarization-activated cationic currents (Ih) affected the mirror function between the pairs of neocortical neurons coupled by STDP.

Imaging regional metabolic changes in the ischemic rat heart in vivo using hyperpolarized(1-13C)Pyruvate

DEFF Research Database (Denmark)

Lauritzen, Mette Hauge; Magnusson, Peter; Laustsen, Christoffer

2017-01-01

in the in vivo rat heart in an open-chest model of ischemia reperfusion. Hyperpolarized MRI enables new possibilities for evaluating changes in cardiac metabolism noninvasively and in real time, which potentially could be used for research to evaluate new treatments and metabolic interventions for myocardial......We evaluated the use of hyperpolarized 13C magnetic resonance imaging (MRI) in an open-chest rat model of myocardial infarction to image regional changes in myocardial metabolism. In total, 10 rats were examined before and after 30 minutes of occlusion of the left anterior descending coronary...

T-dependent B-cell activation is signalled by an early increase in potassium influx

DEFF Research Database (Denmark)

Owens, T; Kaplan, J G

1982-01-01

both by incorporation of 3H-thymidine after 48 h of culture and by uptake of potassium (measured as 86Rb) after 15 h. Analysis of metaphase chromosomes stained with Hoechst dye 33258 from co-cultured T-enriched and nude lymphocytes (from female and male donors, respectively) mixed in the proportion 1...

Time-dependent restricted-active-space self-consistent-field theory for laser-driven many-electron dynamics

DEFF Research Database (Denmark)

Miyagi, Haruhide; Madsen, Lars Bojer

2013-01-01

We present the time-dependent restricted-active-space self-consistent-field (TD-RASSCF) theory as a framework for the time-dependent many-electron problem. The theory generalizes the multiconfigurational time-dependent Hartree-Fock (MCTDHF) theory by incorporating the restricted-active-space scheme...... well known in time-independent quantum chemistry. Optimization of the orbitals as well as the expansion coefficients at each time step makes it possible to construct the wave function accurately while using only a relatively small number of electronic configurations. In numerical calculations of high...

Renal MR angiography and perfusion in the pig using hyperpolarized water

DEFF Research Database (Denmark)

Lipsø, Hans Kasper Wigh; Hansen, Esben Søvsø Szocska; Tougaard, Rasmus Stilling

2016-01-01

at 3 Tesla (T). Approximately 15 mL of hyperpolar-ized water was injected in the renal artery by hand over 4–5 s.Results: A liquid state polarization of 5.3 6 0.9% of 3.8 M pro-tons in 15 mL of deuterium oxide was achieved with a T1of24 6 1 s. This allowed injection through an arterial catheterinto...

Hyperpolarized 3He apparent diffusion coefficient MRI of the lung: reproducibility and volume dependency in healthy volunteers and patients with emphysema

DEFF Research Database (Denmark)

Diaz, S.; Casselbrant, I.; Piitulainen, E.

2008-01-01

PURPOSE: To measure the apparent diffusion coefficient (ADC) of hyperpolarized (HP) (3)He gas using diffusion weighted MRI in healthy volunteers and patients with emphysema and examine the reproducibility and volume dependency. MATERIALS AND METHODS: A total of eight healthy volunteers and 16...... patients with emphysema were examined after inhalation of HP (3)He gas mixed with nitrogen (N(2)) during breathhold starting from functional residual capacity (FRC) in supine position. Coronal diffusion-sensitized MR images were acquired. Each subject was imaged on three separate days over a seven...... in mean ADC with increased inhaled gas volume was observed in both groups. CONCLUSION: Mean ADC and SD of HP (3)He MRI is reproducible and discriminates well between healthy controls and patients with emphysema at the higher gas volume. This method is robust and may be useful to gain new insights...

Search after new agents for hyperpolarization-activated and cyclic nucleotide-gated ion channels; Suche nach neuen Wirkstoffen fuer Hyperpolarisationsaktivierte und zyklisch Nukleotid-gesteuerte Ionenkanaele

Energy Technology Data Exchange (ETDEWEB)

Struenker, T.

2005-12-01

Rhythmic activity of single cells or cellular networks is a common feature of most organisms. Cellular rhythms govern the beating of the heart, cycles of sleep and wakefulness, breathing, and the release of hormones. The endogenous rhythmic activity of many neurons and cardiac relies on a complex interplay between several distinct ion channels. In particular, one type of ion channel plays a prominent role in the control of rhythmic electrical activity because it determines the frequency of the oscillations. The activity of the channels is thus setting the ''pace'' of the activity; therefore, these channels are often referred to as ''pacemaker'' channels. Despite their obvious physiological importance it hasn't been until a few years ago that the genes encoding pacemaker channels have been identified. Because both hyperpolarization and cyclic nucleotides are key elements that control their activity, pacemaker channels have now been designated hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. From a scientific as well as medical point of view, HCN channels are interesting drug targets. Only a few substances are known that specifically affect HCN channels. In the present study, a microtiter plate-based high throughput screening assay for HCN1 and HCN4 channels was developed. With this assay, known drugs for HCN channels were characterized. Subsequently, venoms of snails, spiders, scorpions, and snakes were screened for toxins affecting HCN channel activity. A few venoms were identified that possibly contain drugs that act on HCN channels. (orig.)

Homogeneous catalysis of deuterium transfer by potassium hydroxide and potassium methoxide D2-H2O and D2-CH3OH exchange

International Nuclear Information System (INIS)

Strathdee, G.G.; Garner, D.M.; Given, R.M.

1977-01-01

The kinetics and mechanism of exchange of deuterium between D 2 and water and between D 2 and methanol, catalyzed respectively by concentrated potassium hydroxide and potassium methoxide, has been studied between 348 and 398 K. In the D 2 -KOH-H 2 O case, the transfer of deuterium was found to be controlled by the rate of activation of the D 2 molecule by OH - . Rapid exchange of D + with the aqueous solution followed. From the D 2 -KOCH 3 -CH 3 OH studies, it was concluded that deuterium exchange depended upon the rates of both D 2 activation by methoxide and interaction of the solvent with the transition, or encounter, complex. The dependence of second-order rate constants on solvent activity for both systems was determined by normalization of the exchange reaction rates to unit reagent activity. Analysis of the kinetic isotope effects for each system suggested that their increase with base concentration or temperature was due to solvation effects. (author)

Renal MR angiography and perfusion in the pig using hyperpolarized water.

Science.gov (United States)

Wigh Lipsø, Kasper; Hansen, Esben Søvsø Szocska; Tougaard, Rasmus Stilling; Laustsen, Christoffer; Ardenkjaer-Larsen, Jan Henrik

2017-09-01

To study hyperpolarized water as an angiography and perfusion tracer in a large animal model. Protons dissolved in deuterium oxide (D 2 O) were hyperpolarized in a SPINlab dissolution dynamic nuclear polarization (dDNP) polarizer and subsequently investigated in vivo in a pig model at 3 Tesla (T). Approximately 15 mL of hyperpolarized water was injected in the renal artery by hand over 4-5 s. A liquid state polarization of 5.3 ± 0.9% of 3.8 M protons in 15 mL of deuterium oxide was achieved with a T 1 of 24 ± 1 s. This allowed injection through an arterial catheter into the renal artery and subsequently high-contrast imaging of the entire kidney parenchyma over several seconds. The dynamic images allow quantification of tissue perfusion, with a mean cortical perfusion of 504 ± 123 mL/100 mL/min. Hyperpolarized water MR imaging was successfully demonstrated as a renal angiography and perfusion method. Quantitative perfusion maps of the kidney were obtained in agreement with literature and control experiments with gadolinium contrast. Magn Reson Med 78:1131-1135, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Molecular MRI in the Earth's Magnetic Field Using Continuous Hyperpolarization of a Biomolecule in Water.

Science.gov (United States)

Rovedo, Philipp; Knecht, Stephan; Bäumlisberger, Tim; Cremer, Anna Lena; Duckett, Simon B; Mewis, Ryan E; Green, Gary G R; Burns, Michael; Rayner, Peter J; Leibfritz, Dieter; Korvink, Jan G; Hennig, Jürgen; Pütz, Gerhard; von Elverfeldt, Dominik; Hövener, Jan-Bernd

2016-06-30

In this work, we illustrate a method to continuously hyperpolarize a biomolecule, nicotinamide, in water using parahydrogen and signal amplification by reversible exchange (SABRE). Building on the preparation procedure described recently by Truong et al. [ J. Phys. Chem. B , 2014 , 118 , 13882 - 13889 ], aqueous solutions of nicotinamide and an Ir-IMes catalyst were prepared for low-field NMR and MRI. The (1)H-polarization was continuously renewed and monitored by NMR experiments at 5.9 mT for more than 1000 s. The polarization achieved corresponds to that induced by a 46 T magnet (P = 1.6 × 10(-4)) or an enhancement of 10(4). The polarization persisted, although reduced, if cell culture medium (DPBS with Ca(2+) and Mg(2+)) or human cells (HL-60) were added, but was no longer observable after the addition of human blood. Using a portable MRI unit, fast (1)H-MRI was enabled by cycling the magnetic field between 5 mT and the Earth's field for hyperpolarization and imaging, respectively. A model describing the underlying spin physics was developed that revealed a polarization pattern depending on both contact time and magnetic field. Furthermore, the model predicts an opposite phase of the dihydrogen and substrate signal after one exchange, which is likely to result in the cancelation of some signal at low field.

KV7 potassium channels

DEFF Research Database (Denmark)

Stott, Jennifer B; Jepps, Thomas Andrew; Greenwood, Iain A

2014-01-01

Potassium channels are key regulators of smooth muscle tone, with increases in activity resulting in hyperpolarisation of the cell membrane, which acts to oppose vasoconstriction. Several potassium channels exist within smooth muscle, but the KV7 family of voltage-gated potassium channels have been...

Dependence of the concentrations of "1"3"7Cs and potassium in extracted soil solutions on soil humidity before centrifugation

International Nuclear Information System (INIS)

Prorok, V.V.; Datsenko, O.Yi.; Bulavyin, L.A.; Zlens'kij, S.Je.; Melnichenko, L.Yu.; Rozuvan, S.G.; Poperenko, L.V.; White, P.J.

2017-01-01

Concentrations of 137Cs and potassium in solutions extracted by centrifugation from soils selected at some experimental sites in the 10-km Exclusion Zone of Chornobyl Nuclear Plant were determined. The results showed that for the majority of investigated soils, the concentration of 137Cs in soil solution depends on the humidity of the soil before centrifugation. It is possible to explain the dependence of the concentration of 137Cs in the soil solution on soil humidity from the dependence of the concentrations of molecules of different molecular-gravimetric fractions in soil solution on soil humidity. Considerable amount of 137Cs in soil solution is associated with these molecules, that is why the concentration of 137Cs in the extracted soil solution changes with the humidity of soil. These dependences differ between soils. For the majority of investigated soils the concentration of 137Cs in the extracted soil solution increases with increasing humidity of the soil. By contrast, soil humidity had no effect on the potassium concentration in the extracted soil solution for any soil investigated. It is concluded, that potassium is practically not associated with molecules of different molecular-gravimetric fractions in the extracted soil solutions

Electrolyte Balance of the Inner Ear Investigated by Neutron Activation Analysis of the Sodium and Potassium Content

International Nuclear Information System (INIS)

Ördögh, Mary; Miriszlai, E.

1967-01-01

Even the few experimental data that have been obtained from investigations of the inner ear are an important contribution to our biochemical knowledge of the sense organs. The apparent discrepancies between some experimental results have prompted comparative studies on the sodium and potassium concentrations in the inner-ear fluids, the liquor cerebrospinalis, the mammalian and human serum. The results of these studies are expected to give a good approximation of the intracellular and extracellular electrolyte concentrations and to yield important information on the physiological and pathological conditions of the inner ear as well as on the mechanism of hearing. The experimental material is obtained from guinea pigs by penetration through the round window (fenestra rotunda). The sodium and potassium content is determined by neutron activation analysis. Potassium is precipitated from the irradiated samples by sodium tetraphenyl borate reagent, so that the sodium activity retained by the filtrate can be directly counted. Since a single precipitation of potassium does not yield end products free from sodium contamination, the precipitate is dissolved in acetone and precipitated again with sodium tetraphenyl borate. The product of the second precipitation is radiochemically pure. In simultaneous experiments, potassium was separated from the much higher sodium activity by isotopic exchange. The irradiated sample is added to an experimentally determined inactive potassium tetraphenyl borate precipitate that adsorbs the total potassium activity present without adsorbing any sodium. The separation of potassium by isotopic exchange has the advantage of yielding in a single step a sufficiently pure product without any sodium contamination. For comparison, sodium and potassium were also determined by flame photometry. (author)

Hyperpolarized Water Perfusion in the Porcine Brain – a Pilot Study

DEFF Research Database (Denmark)

Søvsø Szocska Hansen, Esben; Lipsø, Hans Kasper Wigh; Tougaard, Rasmus Stilling

2017-01-01

Dynamic Contrast-Enhanced MR (DCE-MR) perfusion assessment with gadolinium contrast agents is currently the most widely used cerebral perfusion MR method. Hyperpolarized water has recently been shown to succeed 13C probes as angiography probe. In this study, we demonstrate the feasibility...... of hyperpolarized water for visualizing the brain vasculature of a large animal in a clinically relevant setting. In detail, reference perfusion values were obtained and large to small arteries could be identified....

Quantification of in vivo metabolic kinetics of hyperpolarized pyruvate in rat kidneys using dynamic 13C MRSI.

Science.gov (United States)

Xu, Tao; Mayer, Dirk; Gu, Meng; Yen, Yi-Fen; Josan, Sonal; Tropp, James; Pfefferbaum, Adolf; Hurd, Ralph; Spielman, Daniel

2011-10-01

With signal-to-noise ratio enhancements on the order of 10,000-fold, hyperpolarized MRSI of metabolically active substrates allows the study of both the injected substrate and downstream metabolic products in vivo. Although hyperpolarized [1-(13)C]pyruvate, in particular, has been used to demonstrate metabolic activities in various animal models, robust quantification and metabolic modeling remain important areas of investigation. Enzyme saturation effects are routinely seen with commonly used doses of hyperpolarized [1-(13)C]pyruvate; however, most metrics proposed to date, including metabolite ratios, time-to-peak of metabolic products and single exchange rate constants, fail to capture these saturation effects. In addition, the widely used small-flip-angle excitation approach does not correctly model the inflow of fresh downstream metabolites generated proximal to the target slice, which is often a significant factor in vivo. In this work, we developed an efficient quantification framework employing a spiral-based dynamic spectroscopic imaging approach. The approach overcomes the aforementioned limitations and demonstrates that the in vivo (13)C labeling of lactate and alanine after a bolus injection of [1-(13)C]pyruvate is well approximated by saturatable kinetics, which can be mathematically modeled using a Michaelis-Menten-like formulation, with the resulting estimated apparent maximal reaction velocity V(max) and apparent Michaelis constant K(M) being unbiased with respect to critical experimental parameters, including the substrate dose, bolus shape and duration. Although the proposed saturatable model has a similar mathematical formulation to the original Michaelis-Menten kinetics, it is conceptually different. In this study, we focus on the (13)C labeling of lactate and alanine and do not differentiate the labeling mechanism (net flux or isotopic exchange) or the respective contribution of various factors (organ perfusion rate, substrate transport

Potassium fluorotitanate preparation

International Nuclear Information System (INIS)

Perillo, Patricia; Ares, Osvaldo; Botbol, Jose.

1989-01-01

In order to determine the best conditions for potassium fluotitanate preparation as intermediate step in the electrolytic production of metalic titanium, the effects of a number of experimental variables have been studied. This method is a process of sintering titanium dioxide with potassium fluosilicate and potassium chloride, followed by leaching with boiling water and further crystallization by cooling the solution. An overall yield of 90% has been attained under the following conditions: working temperature: 750 deg C; heating time for sintering: 3 hours; molar ratio: titanium dioxide: potassium fluosilicate: potassium chloride: 1 : 2 : 0.4; number of leachings: 6. (Author) [es

Preparation of High specific activity of ''51 Cr by the Szilard-Chalmers effect on potassium chromate

Energy Technology Data Exchange (ETDEWEB)

Barrachina Gomez, M; Villar Castejon, M A

1965-07-01

The {sup 5}1 Cr enriched Cr{sup 3}+ ions, which appear on putting into solution the potassium chromate irradiated with neutrons, are separated as chromium hydroxide. The CrO{sub 4}{sup 2}- ions occluded by the precipitate are eliminated on re precipitating the hydroxide. The more convenient irradiation time to for the production of {sup 5}1 Cr has been determined as the position of the maximum in the experimental curve P=f(t), where the time-dependent index P used is defined as the product of the number. (Author) 13 refs.

Potassium effect on cesium 137 behaviour in natural waters of contaminated regions (Belarus)

International Nuclear Information System (INIS)

Kudel'skij, A.V.; Pashkevich, V.I.; Ovsyannikova, S.V.; Petrovich, A.A.; Smit, D.T.

1998-01-01

Very close relationships between cesium 137 activity of water objects (soil solutions, bog and lake water) and their stable potassium contents have been revealed in the contaminated area in south-eastern Belarus. It was revealed the increase of cesium 137 activity in soil solutions and bog ecosystems proportionally with the increase of potassium content. The exponential dependence of cesium 137 activity of fish production was similar to reverse. The coefficient of cesium 137 accumulation in plants was estimated to be reverse connected with the potassium content in soils. So an universal character of these relations and their specificity are of interest when elaborating countermeasures for reducing population dose loads due to cesium 137 water migration

Kaempferol stimulates large conductance Ca2+-activated K+ (BKCa) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway

Science.gov (United States)

Xu, Y C; Leung, G P H; Wong, P Y D; Vanhoutte, P M; Man, R Y K

2008-01-01

Background and purpose: Kaempferol has been shown to possess a vasodilator effect but its mechanism of action remains unclear. In this study, experiments were carried out to study the effect of kaempferol on K+ channels in endothelial cells. Experimental approach: K+ channel activities in human umbilical vein endothelial cells (HUVECs) were studied by conventional whole cell and cell-attached patch-clamp electrophysiology. Key results: Kaempferol stimulated an outward-rectifying current in HUVECs in a dose-dependent manner with an EC50 value of 2.5±0.02 μM. This kaempferol-induced current was abolished by large conductance Ca2+-activated K+ (BKCa) channel blockers, such as iberiotoxin (IbTX) and charybdotoxin (ChTX), whereas the small conductance Ca2+-activated K+ (SKCa) channel blocker, apamin, and the voltage-dependent K+ (KV) channel blocker, 4-aminopyridine, had no effect. Cell-attached patches demonstrated that kaempferol increased the open probability of BkCa channels in HUVECs. Clamping intracellular Ca2+ did not prevent kaempferol-induced increases in outward current. In addition, the kaempferol-induced current was diminished by the adenylyl cyclase inhibitor SQ22536, the cAMP antagonist Rp-8-Br-cAMP and the PKA inhibitor KT5720, but was not affected by the guanylyl cyclase inhibitor ODQ, the cGMP antagonist Rp-8-Br-cGMP and the PKG inhibitor KT5823. The activation of BKCa channels by kaempferol caused membrane hyperpolarization of HUVECs. Conclusion and implications: These results demonstrate that kaempferol activates the opening of BKCa channels in HUVECs via a cAMP/PKA-dependent pathway, resulting in membrane hyperpolarization. This mechanism may partly account for the vasodilator effects of kaempferol. PMID:18493242

Assessing the transport rate of hyperpolarized pyruvate and lactate from the intra- to the extracellular space.

Science.gov (United States)

Reineri, Francesca; Daniele, Valeria; Cavallari, Eleonora; Aime, Silvio

2016-08-01

The use of [1-(13) C]pyruvate hyperpolarized by means of dynamic nuclear polarization provides a direct way to track the metabolic transformations of this metabolite in vivo and in cell cultures. The identification of the intra- and extracellular contributions to the (13) C NMR resonances is not straightforward. In order to obtain information about the rate of pyruvate and lactate transport through the cellular membrane, we set up a method that relies on the sudden 'quenching' of the extracellular metabolites' signal. The paramagnetic Gd-tetraazacyclododecane triacetic acid (Gd-DO3A) complex was used to dramatically decrease the longitudinal relaxation time constants of the (13) C-carboxylate resonances of both pyruvate and lactate. When Gd-DO3A was added to an MCF-7 cellular culture, which had previously received a dose of hyperpolarized [1-(13) C]pyruvate, the contributions of the extracellular pyruvate and lactate signals were deleted. From the analysis of the decay curves of the (13) C-carboxylate resonances of pyruvate and lactate it was possible to extract information about the exchange rate of the two metabolites across the cellular membrane. In particular, it was found that, in the reported experimental conditions, the lactate transport from the intra- to the extracellular space is not much lower than the rate of lactate formation. The method reported herein is non-destructive and it could be translated to in vivo studies. It opens a route for the use of hyperpolarized pyruvate to assess altered activity of carboxylate transporter proteins that may occur in pathological conditions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Potassium Chloride Versus Voltage Clamp Contractures in Ventricular Muscle

Science.gov (United States)

Morad, M.; Reeck, S.; Rao, M.

1981-01-01

In frog ventricle, developed tension was markedly larger in response to depolarization caused by a voltage clamp step than to depolarization induced by high concentrations of potassium chloride. Measurement of extracellular potassium activity at the surface and at the depth of muscle during the development of contractures showed that the diffusion of potassium is much slower than the spread of depolarization through the cross section of muscle. These two observations suggest that competition between the depolarizing and the negative inotropic effects of an increase in the extracellular potassium ion concentration may determine the time course and magnitude of contractile tension in heart muscle.

T1 nuclear magnetic relaxation dispersion of hyperpolarized sodium and cesium hydrogencarbonate-13 C.

Science.gov (United States)

Martínez-Santiesteban, Francisco M; Dang, Thien Phuoc; Lim, Heeseung; Chen, Albert P; Scholl, Timothy J

2017-09-01

In vivo pH mapping in tissue using hyperpolarized hydrogencarbonate- 13 C has been proposed as a method to study tumor growth and treatment and other pathological conditions related to pH changes. The finite spin-lattice relaxation times (T 1 ) of hyperpolarized media are a significant limiting factor for in vivo imaging. Relaxation times can be measured at standard magnetic fields (1.5 T, 3.0 T etc.), but no such data are available at low fields, where T 1 values can be significantly shorter. This information is required to determine the potential loss of polarization as the agent is dispensed and transported from the polarizer to the MRI scanner. The purpose of this study is to measure T 1 dispersion from low to clinical magnetic fields (0.4 mT to 3.0 T) of different hyperpolarized hydrogencarbonate formulations previously proposed in the literature for in vivo pH measurements. 13 C-enriched cesium and sodium hydrogencarbonate preparations were hyperpolarized using dynamic nuclear polarization, and the T 1 values of different samples were measured at different magnetic field strengths using a fast field-cycling relaxometer and a 3.0 T clinical MRI system. The effects of deuterium oxide as a dissolution medium for sodium hydrogencarbonate were also analyzed. This study finds that the cesium formulation has slightly shorter T 1 values compared with the sodium preparation. However, the higher solubility of cesium hydrogencarbonate- 13 C means it can be polarized at greater concentration, using less trityl radical than sodium hydrogencarbonate- 13 C. This study also establishes that the preparation and handling of sodium hydrogencarbonate formulations in relation to cesium hydrogencarbonate is more difficult, due to the higher viscosity and lower achievable concentrations, and that deuterium oxide significantly increases the T 1 of sodium hydrogencarbonate solutions. Finally, this work also investigates the influence of pH on the spin-lattice relaxation of cesium

Reaction of lithium, sodium and potassium polyphosphates with potassium permanganate at elevated temperatures

International Nuclear Information System (INIS)

Paderova, L.V.; Onuchina, T.V.; Kochergin, V.P.

1996-01-01

A study was made on destruction of molten polyphosphates of alkaline metals by potassium permanganate during change of KMnO 4 content, test time and temperature. Ortho-, di, tri- and tetraphosphate-anions, as well as manganese compounds with different oxidation degree were revealed in products of component interaction. Empirical equations of the dependence of the value of average molecular mass on change of melt temperature were derived. 11 refs.; 2 figs.; 2 tabs

Continuous hyperpolarization with parahydrogen in a membrane reactor

Science.gov (United States)

Lehmkuhl, Sören; Wiese, Martin; Schubert, Lukas; Held, Mathias; Küppers, Markus; Wessling, Matthias; Blümich, Bernhard

2018-06-01

Hyperpolarization methods entail a high potential to boost the sensitivity of NMR. Even though the "Signal Amplification by Reversible Exchange" (SABRE) approach uses para-enriched hydrogen, p-H2, to repeatedly achieve high polarization levels on target molecules without altering their chemical structure, such studies are often limited to batch experiments in NMR tubes. Alternatively, this work introduces a continuous flow setup including a membrane reactor for the p-H2, supply and consecutive detection in a 1 T NMR spectrometer. Two SABRE substrates pyridine and nicotinamide were hyperpolarized, and more than 1000-fold signal enhancement was found. Our strategy combines low-field NMR spectrometry and a membrane flow reactor. This enables precise control of the experimental conditions such as liquid and gas pressures, and volume flow for ensuring repeatable maximum polarization.

Integrated process using non-stoichiometric sulfides or oxides of potassium for making less active metals and hydrocarbons

International Nuclear Information System (INIS)

Swanson, R.

1984-01-01

Disclosed is a combinative integrated chemical process using inorganic reactants and yielding, if desired, organic products. The process involves first the production of elemental potassium by the thermal or thermal-reduced pressure decomposition of potassium oxide or potassium sulfide and distillation of the potassium. This elemental potassium is then used to reduce ores or ore concentrates of copper, zinc, lead, magnesium, cadmium, iron, arsenic, antimony or silver to yield one or more of these less active metals in elemental form. Process potassium can also be used to produce hydrogen by reaction with water or potassium hydroxide. This hydrogen is reacted with potassium to produce potassium hydride. Heating the latter with carbon produces potassium acetylide which forms acetylene when treated with water. Acetylene is hydrogenated to ethene or ethane with process hydrogen. Using Wurtz-Fittig reaction conditions, the ethane can be upgraded to a mixture of hydrocarbons boiling in the fuel range

Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate

DEFF Research Database (Denmark)

Nelson, Sarah J; Kurhanewicz, John; Vigneron, Daniel B

2013-01-01

This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-¹³C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-f...

Hyperpolarized [U-(2) H, U-(13) C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells.

Science.gov (United States)

Timm, Kerstin N; Hartl, Johannes; Keller, Markus A; Hu, De-En; Kettunen, Mikko I; Rodrigues, Tiago B; Ralser, Markus; Brindle, Kevin M

2015-12-01

A resonance at ∼181 ppm in the (13) C spectra of tumors injected with hyperpolarized [U-(2) H, U-(13) C]glucose was assigned to 6-phosphogluconate (6PG), as in previous studies in yeast, whereas in breast cancer cells in vitro this resonance was assigned to 3-phosphoglycerate (3PG). These peak assignments were investigated here using measurements of 6PG and 3PG (13) C-labeling using liquid chromatography tandem mass spectrometry (LC-MS/MS) METHODS: Tumor-bearing mice were injected with (13) C6 glucose and the (13) C-labeled and total 6PG and 3PG concentrations measured. (13) C MR spectra of glucose-6-phosphate dehydrogenase deficient (zwf1Δ) and wild-type yeast were acquired following addition of hyperpolarized [U-(2) H, U-(13) C]glucose and again (13) C-labeled and total 6PG and 3PG were measured by LC-MS/MS RESULTS: Tumor (13) C-6PG was more abundant than (13) C-2PG/3PG and the resonance at ∼181 ppm matched more closely that of 6PG. (13) C MR spectra of wild-type and zwf1Δ yeast cells showed a resonance at ∼181 ppm after labeling with hyperpolarized [U-(2) H, U-(13) C]glucose, however, there was no 6PG in zwf1Δ cells. In the wild-type cells 3PG was approximately four-fold more abundant than 6PG CONCLUSION: The resonance at ∼181 ppm in (13) C MR spectra following injection of hyperpolarized [U-(2) H, U-(13) C]glucose originates predominantly from 6PG in EL4 tumors and 3PG in yeast cells. © 2014 Wiley Periodicals, Inc.

Time-dependent restricted-active-space self-consistent-field theory for bosonic many-body systems

International Nuclear Information System (INIS)

Lévêque, Camille; Madsen, Lars Bojer

2017-01-01

We develop an ab initio time-dependent wavefunction based theory for the description of a many-body system of cold interacting bosons. Like the multi-configurational time-dependent Hartree method for bosons (MCTDHB), the theory is based on a configurational interaction Ansatz for the many-body wavefunction with time-dependent self-consistent-field orbitals. The theory generalizes the MCTDHB method by incorporating restrictions on the active space of the orbital excitations. The restrictions are specified based on the physical situation at hand. The equations of motion of this time-dependent restricted-active-space self-consistent-field (TD-RASSCF) theory are derived. The similarity between the formal development of the theory for bosons and fermions is discussed. The restrictions on the active space allow the theory to be evaluated under conditions where other wavefunction based methods due to exponential scaling in the numerical effort cannot, and to clearly identify the excitations that are important for an accurate description, significantly beyond the mean-field approach. For ground state calculations we find it to be important to allow a few particles to have the freedom to move in many orbitals, an insight facilitated by the flexibility of the restricted-active-space Ansatz . Moreover, we find that a high accuracy can be obtained by including only even excitations in the many-body self-consistent-field wavefunction. Time-dependent simulations of harmonically trapped bosons subject to a quenching of their noncontact interaction, show failure of the mean-field Gross-Pitaevskii approach within a fraction of a harmonic oscillation period. The TD-RASSCF theory remains accurate at much reduced computational cost compared to the MCTDHB method. Exploring the effect of changes of the restricted-active-space allows us to identify that even self-consistent-field excitations are mainly responsible for the accuracy of the method. (paper)

Pb2+ Modulates Ca2+ Membrane Permeability In Paramecium

Science.gov (United States)

Bernal-Martínez, Juan; Ortega Soto, Arturo

2004-09-01

Intracellular recording experiments in current clamp configuration were done to evaluate whether Pb2+ modulates ionic membrane permeability in the fresh water Paramecium tetraurelia. It was found that Pb2+ triggers in a dose-dependent manner, a burst of spontaneous action potentials followed by a robust and sustained after hyper-polarization. In addition, Pb2+ increased the frequency of firing the spontaneous Ca2+-Action Potential and also, the duration of Ca2+-Action Potential, in a dose and reversibly-dependent manner. These results suggest that Pb2+ increases calcium membrane permeability of Paramecium and probably activates a calcium-dependent-potassium conductance in the ciliate.

Bradykinin-activated transmembrane signals are coupled via N/sub o/ or N/sub i/ to production of inositol 1,4,5-trisphosphate, a second messenger in NG108-15 neuroblastoma-glioma hybrid cells

International Nuclear Information System (INIS)

Higashida, H.; Streaty, R.A.; Klee, W.; Nirenberg, M.

1986-01-01

The addition of bradykinin to NG108-15 cells results in a transient hyperpolarization followed by prolonged cell depolarization. Injection of inositol 1,4,5-trisphosphate or Ca 2+ into the cytoplasm of NG108-15 cells also elicits cell hyperpolarization followed by depolarization. Tetraethylammonium ions inhibit the hyperpolarizing response of cells to bradykinin or inositol 1,4,5-trisphosphate. Thus, the hyperpolarizing phase of the cell response may be due to inositol 1,4,5-trisphosphate-dependent release of stored 45 Ca-labelled Ca 2+ into the cytoplasm, which activates Ca 2+ -dependent K + channels. The depolarizing phase of the cell response to bradykinin is due largely to inhibition of M channels, thereby decreasing the rate of K + efflux from cells and, to a lesser extent, to activation of Ca 2+ -dependent ion channels and Ca 2+ channels. In contrast, injection of inositol 1,4,5-trisphosphate or Ca 2+ into the cytosol did not alter M channel activity. Incubation of NG108-15 cells with pertussis toxin inhibits bradykinin-dependent cell hyperpolarization and depolarization. Bradykinin stimulates low K/sub m/ GTPase activity and inhibits adenylate cyclase in NG108-15 membrane preparations but not in membranes prepared from cells treated with pertussis toxin. These results show that [bradykinin-receptor] complexes interact with N/sub o/ or N/sub i/ and suggest that N/sub o/ and/or N/sub i/ mediate the transduction of signals from bradykinin receptors to phospholipase C and adenylate cyclase

A continuous-flow, high-throughput, high-pressure parahydrogen converter for hyperpolarization in a clinical setting.

Science.gov (United States)

Hövener, Jan-Bernd; Bär, Sébastien; Leupold, Jochen; Jenne, Klaus; Leibfritz, Dieter; Hennig, Jürgen; Duckett, Simon B; von Elverfeldt, Dominik

2013-02-01

Pure parahydrogen (pH(2) ) is the prerequisite for optimal pH(2) -based hyperpolarization experiments, promising approaches to access the hidden orders of magnitude of MR signals. pH(2) production on-site in medical research centers is vital for the proliferation of these technologies in the life sciences. However, previously suggested designs do not meet our requirements for safety or production performance (flow rate, pressure or enrichment). In this article, we present the safety concept, design and installation of a pH(2) converter, operated in a clinical setting. The apparatus produces a continuous flow of four standard liters per minute of ≈98% enriched pH(2) at a pressure maximum of 50 bar. The entire production cycle, including cleaning and cooling to 25 K, takes less than 5 h, only ≈45 min of which are required for actual pH(2) conversion. A fast and simple quantification procedure is described. The lifetimes of pH(2) in a glass vial and aluminum storage cylinder are measured to be T(1C) (glass vial) =822 ± 29 min and T(1C) (Al cylinder) =129 ± 36 days, thus providing sufficiently long storage intervals and allowing the application of pH(2) on demand. A dependence of line width on pH(2) enrichment is observed. As examples, (1) H hyperpolarization of pyridine and (13) C hyperpolarization of hydroxyethylpropionate are presented. Copyright © 2012 John Wiley & Sons, Ltd.

Study of Activated Carbons by Pyrolysis of Mangifera Indica Seed (Mango in Presence of Sodium and Potassium Hydroxide

Directory of Open Access Journals (Sweden)

J. C. Moreno-Piraján

2012-01-01

Full Text Available Activated carbons (ACs were prepared by pyrolysis of seeds mango in presence of sodium and potassium hydroxide (chemical activities. Seeds mango from Colombian Mango cultives were impregnated with aqueous solutions of NaOH and KOH following a variant of the incipient wetness method. Different concentrations were used to produce impregnation ratios of 3:1 (weight terms. Activation was carried out under argon flow by heating to 823 K with 1 h soaking time. The porous texture of the obtained ACs was characterized by physical adsorptions of N2 at 77 K and CO2 at 273 K. The impregnation ration and hydroxide type had a strong influence on the pore structure of these ACs, which could be easily controlled by simply varying the proportion of the hydroxides used in the activation. Thus, the development of porosity for precursors with low structural order (high reactivity is better with NaOH than KOH, whereas the opposite is observed for the highly ordered ones. Variable adsorption capacities and porosity distributions can be achieved depending on the activating agent selected. In general, KOH produces activated carbons with narrower micropore distributions than those prepared by NaOH.

Effects of Arousal on Mouse Sensory Cortex Depend on Modality

Directory of Open Access Journals (Sweden)

Daisuke Shimaoka

2018-03-01

Full Text Available Summary: Changes in arousal modulate the activity of mouse sensory cortex, but studies in different mice and different sensory areas disagree on whether this modulation enhances or suppresses activity. We measured this modulation simultaneously in multiple cortical areas by imaging mice expressing voltage-sensitive fluorescent proteins (VSFP. VSFP imaging estimates local membrane potential across large portions of cortex. We used temporal filters to predict local potential from running speed or from pupil dilation, two measures of arousal. The filters provided good fits and revealed that the effects of arousal depend on modality. In the primary visual cortex (V1 and auditory cortex (Au, arousal caused depolarization followed by hyperpolarization. In the barrel cortex (S1b and a secondary visual area (LM, it caused only hyperpolarization. In all areas, nonetheless, arousal reduced the phasic responses to trains of sensory stimuli. These results demonstrate diverse effects of arousal across sensory cortex but similar effects on sensory responses. : Shimaoka et al. use voltage-sensitive imaging to show that the effects of arousal on the mouse cortex are markedly different across areas and over time. In all the sensory areas studied, nonetheless, arousal reduced the phasic voltage responses to trains of sensory stimuli. Keywords: cerebral cortex, cortical state, locomotion, sensory processing, widefield imaging

A comparison of quantitative methods for clinical imaging with hyperpolarized (13)C-pyruvate.

Science.gov (United States)

Daniels, Charlie J; McLean, Mary A; Schulte, Rolf F; Robb, Fraser J; Gill, Andrew B; McGlashan, Nicholas; Graves, Martin J; Schwaiger, Markus; Lomas, David J; Brindle, Kevin M; Gallagher, Ferdia A

2016-04-01

Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized (13)C-labelled molecules, such as the conversion of [1-(13)C]pyruvate to [1-(13)C]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches that accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized (13)C data. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

Inhibitory Effect of Vascular Endothelial Growth Factor on the Slowly Activating Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes.

Science.gov (United States)

Lin, Zhenhao; Xing, Wenlu; Gao, Chuanyu; Wang, Xianpei; Qi, Datun; Dai, Guoyou; Zhao, Wen; Yan, Ganxin

2018-01-26

Vascular endothelial growth factor (VEGF) exerts a number of beneficial effects on ischemic myocardium via its angiogenic properties. However, little is known about whether VEGF has a direct effect on the electrical properties of cardiomyocytes. In the present study, we investigated the effects of different concentrations of VEGF on delayed rectifier potassium currents (I K ) in guinea pig ventricular myocytes and their effects on action potential (AP) parameters. I K and AP were recorded by the whole-cell patch clamp method in ventricular myocytes. Cells were superfused with control solution or solution containing VEGF at different concentrations for 10 minutes before recording. Some ventricular myocytes were pretreated with a phosphatidylinositol 3-kinase inhibitor for 1 hour before the addition of VEGF. We found that VEGF inhibited the slowly activating delayed rectifier potassium current (I K s ) in a concentration-dependent manner (18.13±1.04 versus 12.73±0.34, n=5, P =0.001; 12.73±0.34 versus 9.05±1.20, n=5, P =0.036) and prolonged AP duration (894.5±36.92 versus 746.3±33.71, n=5, P =0.021). Wortmannin, a phosphatidylinositol 3-kinase inhibitor, eliminated these VEGF-induced effects. VEGF had no significant effect on the rapidly activating delayed rectifier potassium current (I K r ), resting membrane potential, AP amplitude, or maximal velocity of depolarization. VEGF inhibited I K s in a concentration-dependent manner through a phosphatidylinositol 3-kinase-mediated signaling pathway, leading to AP prolongation. The results indicate a promising therapeutic potential of VEGF in prevention of ventricular tachyarrhythmias under conditions of high sympathetic activity and ischemia. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation.

Science.gov (United States)

Tang, Tiantian; Lang, Xueting; Xu, Congfei; Wang, Xiaqiong; Gong, Tao; Yang, Yanqing; Cui, Jun; Bai, Li; Wang, Jun; Jiang, Wei; Zhou, Rongbin

2017-08-04

The NLRP3 inflammasome can sense different pathogens or danger signals, and has been reported to be involved in the development of many human diseases. Potassium efflux and mitochondrial damage are both reported to mediate NLRP3 inflammasome activation, but the underlying, orchestrating signaling events are still unclear. Here we show that chloride intracellular channels (CLIC) act downstream of the potassium efflux-mitochondrial reactive oxygen species (ROS) axis to promote NLRP3 inflammasome activation. NLRP3 agonists induce potassium efflux, which causes mitochondrial damage and ROS production. Mitochondrial ROS then induces the translocation of CLICs to the plasma membrane for the induction of chloride efflux to promote NEK7-NLRP3 interaction, inflammasome assembly, caspase-1 activation, and IL-1β secretion. Thus, our results identify CLICs-dependent chloride efflux as an essential and proximal upstream event for NLRP3 activation.The NLRP3 inflammasome is key to the regulation of innate immunity against pathogens or stress, but the underlying signaling regulation is still unclear. Here the authors show that chloride intracellular channels (CLIC) interface between mitochondria stress and inflammasome activation to modulate inflammatory responses.

GABAergic activities control spike timing- and frequency-dependent long-term depression at hippocampal excitatory synapses

Directory of Open Access Journals (Sweden)

Makoto Nishiyama

2010-06-01

Full Text Available GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and post-synaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and post-synaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABAARs and presynaptic GABABRs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABAAR-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“e-LTD” at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes e-LTD of inputs that induce small postsynaptic currents (<70 pA with LTP timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“e-LTP”. Furthermore, under spike-timing protocols that induce e-LTP and e-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“i-LTP” and “i-LTD” to the same postsynaptic cells. Finally, we show that presynaptic GABABR-mediated inhibition plays a major role in the induction of frequency-dependent e-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing and frequency dependences of long-term synaptic modifications in the hippocampus.

Urinary potassium is a potential biomarker of disease activity in Ulcerative colitis and displays in vitro immunotolerant role.

Science.gov (United States)

Goyal, Sandeep; Rampal, Ritika; Kedia, Saurabh; Mahajan, Sandeep; Bopanna, Sawan; Yadav, Devesh P; Jain, Saransh; Singh, Amit Kumar; Wari, Md Nahidul; Makharia, Govind; Awasthi, Amit; Ahuja, Vineet

2017-12-22

We evaluated the in-vitro effect of potassium on CD4 + T cells and the role of urinary potassium as a potential biomarker of disease activity in patients with ulcerative colitis (UC). This prospective observational cohort study included healthy controls (n = 18) and UC patients [n = 30, median age: 40 (IQR: 28-46) years, 17 males)] with active disease(assessed by Mayo score) from September 2015-May 2016. Twenty-four hours urinary potassium along with fecal calprotectin (FCP) were estimated in UC patients (at baseline and follow-up after 3-6 months) and controls. In healthy volunteers, we also assessed the effect of potassium on CD4 + T cells differentiated in the presence of Th17 polarizing condition. UC patients had significantly higher FCP (368.2 ± 443.04 vs 12.44 ± 27.51, p < 0.001) and significantly lower urinary potassium (26.6 ± 16.9 vs 46.89 ± 35.91, p = 0.01) levels than controls. At follow-up, a significant increase in urinary potassium among patients who had clinical response [n = 22, 21.4 (14.4-39.7) to 36.5 (20.5-61.6), p = 0.04] and remission [n = 12, 18.7 (9.1-34.3) to 36.5 (23.4-70.5), p = 0.05] was accompanied with a parallel decline in FCP. On in-vitro analysis, potassium under Th17 polarizing conditions significantly inhibited IL-17 and interferon-[Formula: see text] expression while favoring the induction of FoxP3 + T cells. Therefore, urinary potassium levels are inversely associated with disease activity in UC with in-vitro data supporting an immune-tolerant role of potassium.

Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint.

Science.gov (United States)

Hatch, R J; Jennings, E A; Ivanusic, J J

2013-08-01

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih ) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system. © 2012 European Federation of International Association for the Study of Pain Chapters.

Lactococcin G is a potassium ion-conducting, two-component bacteriocin.

Science.gov (United States)

Moll, G; Ubbink-Kok, T; Hildeng-Hauge, H; Nissen-Meyer, J; Nes, I F; Konings, W N; Driessen, A J

1996-02-01

Lactococcin G is a novel lactococcal bacteriocin whose activity depends on the complementary action of two peptides, termed alpha and beta. Peptide synthesis of the alpha and beta peptides yielded biologically active lactococcin G, which was used in mode-of-action studies on sensitive cells of Lactococcus lactis. Approximately equivalent amounts of both peptides were required for optimal bactericidal effect. No effect was observed with either the alpha or beta peptide in the absence of the complementary peptide. The combination of alpha and beta peptides (lactococcin G) dissipates the membrane potential (delta omega), and as a consequence cells release alpha-aminoisobutyrate, a non-metabolizable alanine analog that is accumulated through a proton motive-force dependent mechanism. In addition, the cellular ATP level is dramatically reduced, which results in a drastic decrease of the ATP-driven glutamate uptake. Lactococcin G does not form a proton-conducting pore, as it has no effect on the transmembrane pH gradient. Dissipation of the membrane potential by uncouplers causes a slow release of potassium (rubidium) ions. However, rapid release of potassium was observed in the presence of lactococcin G. These data suggest that the bactericidal effect of lactococcin G is due to the formation of potassium-selective channels by the alpha and beta peptides in the target bacterial membrane.

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.

Modeling non-linear kinetics of hyperpolarized [1-(13)C] pyruvate in the crystalloid-perfused rat heart

NARCIS (Netherlands)

Mariotti, E.; Orton, M. R.; Eerbeek, O.; Ashruf, J. F.; Zuurbier, C. J.; Southworth, R.; Eykyn, T. R.

2016-01-01

Hyperpolarized (13)C MR measurements have the potential to display non-linear kinetics. We have developed an approach to describe possible non-first-order kinetics of hyperpolarized [1-(13)C] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass

Novel time-dependent vascular actions of Δ9-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma

International Nuclear Information System (INIS)

O'Sullivan, Saoirse E.; Tarling, Elizabeth J.; Bennett, Andrew J.; Kendall, David A.; Randall, Michael D.

2005-01-01

Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, Δ 9 -tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPARγ). In vitro, THC (10 μM) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPARγ agonist rosiglitazone and was inhibited by the PPARγ antagonist GW9662 (1 μM), but not the cannabinoid CB 1 receptor antagonist AM251 (1 μM). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPARγ, transiently expressed in combination with retinoid X receptor α and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 μM). In vitro incubation with THC (1 or 10 μM, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPARγ ligands. The present results provide strong evidence that THC is a PPARγ ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of cannabis may be mediated by nuclear receptors

Preservation of endothelium-dependent relaxation in atherosclerotic mice with endothelium-restricted endothelin-1 overexpression.

Science.gov (United States)

Mian, Muhammad Oneeb Rehman; Idris-Khodja, Noureddine; Li, Melissa W; Leibowitz, Avshalom; Paradis, Pierre; Rautureau, Yohann; Schiffrin, Ernesto L

2013-10-01

In human atherosclerosis, which is associated with elevated plasma and coronary endothelin (ET)-1 levels, ETA receptor antagonists improve coronary endothelial function. Mice overexpressing ET-1 specifically in the endothelium (eET-1) crossed with atherosclerosis-prone apolipoprotein E knockout mice (Apoe(-/-)) exhibit exaggerated high-fat diet (HFD)-induced atherosclerosis. Since endothelial dysfunction often precedes atherosclerosis development, we hypothesized that mice overexpressing endothelial ET-1 on a genetic background deficient in apolipoprotein E (eET-1/Apoe(-/-)) would have severe endothelial dysfunction. To test this hypothesis, we investigated endothelium-dependent relaxation (EDR) to acetylcholine in eET-1/Apoe(-/-) mice. EDR in mesenteric resistance arteries from 8- and 16-week-old mice fed a normal diet or HFD was improved in eET-1/Apoe(-/-) compared with Apoe(-/-) mice. Nitric oxide synthase (NOS) inhibition abolished EDR in Apoe(-/-). EDR in eET-1/Apoe(-/-) mice was resistant to NOS inhibition irrespective of age or diet. Inhibition of cyclooxygenase, the cytochrome P450 pathway, and endothelium-dependent hyperpolarization (EDH) resulted in little or no inhibition of EDR in eET-1/Apoe(-/-) compared with wild-type (WT) mice. In eET-1/Apoe(-/-) mice, blocking of EDH or soluble guanylate cyclase (sGC), in addition to NOS inhibition, decreased EDR by 36 and 30%, respectively. The activation of 4-aminopyridine-sensitive voltage-dependent potassium channels (Kv) during EDR was increased in eET-1/Apoe(-/-) compared with WT mice. We conclude that increasing eET-1 in mice that develop atherosclerosis results in decreased mutual dependence of endothelial signaling pathways responsible for EDR, and that NOS-independent activation of sGC and increased activation of Kv are responsible for enhanced EDR in this model of atherosclerosis associated with elevated endothelial and circulating ET-1.

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

Science.gov (United States)

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

2014-01-01

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

Gabapentin Modulates HCN4 Channel Voltage-Dependence

Directory of Open Access Journals (Sweden)

Han-Shen Tae

2017-08-01

Full Text Available Gabapentin (GBP is widely used to treat epilepsy and neuropathic pain. There is evidence that GBP can act on hyperpolarization-activated cation (HCN channel-mediated Ih in brain slice experiments. However, evidence showing that GBP directly modulates HCN channels is lacking. The effect of GBP was tested using two-electrode voltage clamp recordings from human HCN1, HCN2, and HCN4 channels expressed in Xenopus oocytes. Whole-cell recordings were also made from mouse spinal cord slices targeting either parvalbumin positive (PV+ or calretinin positive (CR+ inhibitory neurons. The effect of GBP on Ih was measured in each inhibitory neuron population. HCN4 expression was assessed in the spinal cord using immunohistochemistry. When applied to HCN4 channels, GBP (100 μM caused a hyperpolarizing shift in the voltage of half activation (V1/2 thereby reducing the currents. Gabapentin had no impact on the V1/2 of HCN1 or HCN2 channels. There was a robust increase in the time to half activation for HCN4 channels with only a small increase noted for HCN1 channels. Gabapentin also caused a hyperpolarizing shift in the V1/2 of Ih measured from HCN4-expressing PV+ inhibitory neurons in the spinal dorsal horn. Gabapentin had minimal effect on Ih recorded from CR+ neurons. Consistent with this, immunohistochemical analysis revealed that the majority of CR+ inhibitory neurons do not express somatic HCN4 channels. In conclusion, GBP reduces HCN4 channel-mediated currents through a hyperpolarized shift in the V1/2. The HCN channel subtype selectivity of GBP provides a unique tool for investigating HCN4 channel function in the central nervous system. The HCN4 channel is a candidate molecular target for the acute analgesic and anticonvulsant actions of GBP.

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 �

Persistence and storage of activity patterns in spiking recurrent cortical networks: modulation of sigmoid signals by after-hyperpolarization currents and acetylcholine.

Science.gov (United States)

Palma, Jesse; Grossberg, Stephen; Versace, Massimiliano

2012-01-01

Many cortical networks contain recurrent architectures that transform input patterns before storing them in short-term memory (STM). Theorems in the 1970's showed how feedback signal functions in rate-based recurrent on-center off-surround networks control this process. A sigmoid signal function induces a quenching threshold below which inputs are suppressed as noise and above which they are contrast-enhanced before pattern storage. This article describes how changes in feedback signaling, neuromodulation, and recurrent connectivity may alter pattern processing in recurrent on-center off-surround networks of spiking neurons. In spiking neurons, fast, medium, and slow after-hyperpolarization (AHP) currents control sigmoid signal threshold and slope. Modulation of AHP currents by acetylcholine (ACh) can change sigmoid shape and, with it, network dynamics. For example, decreasing signal function threshold and increasing slope can lengthen the persistence of a partially contrast-enhanced pattern, increase the number of active cells stored in STM, or, if connectivity is distance-dependent, cause cell activities to cluster. These results clarify how cholinergic modulation by the basal forebrain may alter the vigilance of category learning circuits, and thus their sensitivity to predictive mismatches, thereby controlling whether learned categories code concrete or abstract features, as predicted by Adaptive Resonance Theory. The analysis includes global, distance-dependent, and interneuron-mediated circuits. With an appropriate degree of recurrent excitation and inhibition, spiking networks maintain a partially contrast-enhanced pattern for 800 ms or longer after stimuli offset, then resolve to no stored pattern, or to winner-take-all (WTA) stored patterns with one or multiple winners. Strengthening inhibition prolongs a partially contrast-enhanced pattern by slowing the transition to stability, while strengthening excitation causes more winners when the network

Persistence and storage of activity patterns in spiking recurrent cortical networks:Modulation of sigmoid signals by after-hyperpolarization currents and acetylcholine

Directory of Open Access Journals (Sweden)

Jesse ePalma

2012-06-01

Full Text Available Many cortical networks contain recurrent architectures that transform input patterns before storing them in short-term memory (STM. Theorems in the 1970’s showed how feedback signal functions in rate-based recurrent on-center off-surround networks control this process. A sigmoid signal function induces a quenching threshold below which inputs are suppressed as noise and above which they are contrast-enhanced before pattern storage. This article describes how changes in feedback signaling, neuromodulation, and recurrent connectivity may alter pattern processing in recurrent on-center off-surround networks of spiking neurons. In spiking neurons, fast, medium, and slow after-hyperpolarization (AHP currents control sigmoid signal threshold and slope. Modulation of AHP currents by acetylcholine (ACh can change sigmoid shape and, with it, network dynamics. For example, decreasing signal function threshold and increasing slope can lengthen the persistence of a partially contrast-enhanced pattern, increase the number of active cells stored in STM, or, if connectivity is distance-dependent, cause cell activities to cluster. These results clarify how cholinergic modulation by the basal forebrain may alter the vigilance of category learning circuits, and thus their sensitivity to predictive mismatches, thereby controlling whether learned categories code concrete or abstract features, as predicted by Adaptive Resonance Theory. The analysis includes global, distance-dependent, and interneuron-mediated circuits. With an appropriate degree of recurrent excitation and inhibition, spiking networks maintain a partially contrast-enhanced pattern for 800 milliseconds or longer after stimuli offset, then resolve to no stored pattern, or to winner-take-all stored patterns with one or multiple winners. Strengthening inhibition prolongs a partially contrast-enhanced pattern by slowing the transition to stability, while strengthening excitation causes more winners

Acute hypertensive stress imaged by cardiac hyperpolarized [1-C]pyruvate magnetic resonance

DEFF Research Database (Denmark)

Tougaard, Rasmus Stilling; Hansen, Esben Søvsø Szocska; Laustsen, Christoffer

2018-01-01

PURPOSE: Deranged metabolism is now recognized as a key causal factor in a variety of heart diseases, and is being studied extensively. However, invasive methods may alter metabolism, and conventional imaging techniques measure tracer uptake but not downstream metabolism. These challenges may...... be overcome by hyperpolarized MR, a noninvasive technique currently crossing the threshold into human trials. The aim of this study was to image metabolic changes in the heart in response to endogastric glucose bolus and to acute hypertension. METHODS: Five postprandial pigs were scanned with hyperpolarized.......008) and ejection fraction decreased from 54 ± 2% to 47 ± 6% (P = 0.03) The hemodynamic changes were accompanied by increases in the hyperpolarized [1-13C]pyruvate MR derived ratios of lactate/alanine (from 0.58 ± 0.13 to 0.78 ± 0.06, P = 0.03) and bicarbonate/alanine (from 0.55 ± 0.12 to 0.91 ± 0.14, P = 0...

Time-dependent restricted-active-space self-consistent eld theory: Formulation and application to laser-driven many-electron dynamics

DEFF Research Database (Denmark)

Miyagi, Haruhide; Madsen, Lars Bojer

We have developed a new theoretical framework for time-dependent many-electron problems named time-dependent restricted-active-space self-consistent field (TD-RASSCF) theory. The theory generalizes the multicongurational time-dependent Hartree-Fock (MCTDHF) theory by truncating the expansion...

Hyperpolarized 2-oxoglutarate as metabolic agent in mr

DEFF Research Database (Denmark)

2015-01-01

Hyperpolarized 1-13C-2-oxoglutarate as contrast agent in13C Magnetic Resonance diagnostic technique (13C-MRI) for use in the diagnosis of cancer. In particular, upon administration of said 1-13C-2-oxoglutarate, signals of 1-13C-glutamate are detected. More in particular, different MR signals from13...

Investigating tumor perfusion and metabolism using multiple hyperpolarized 13C compounds: HP001, pyruvate and urea

DEFF Research Database (Denmark)

von Morze, Cornelius; Larson, Peder E.Z.; Hu, Simon

2012-01-01

The metabolically inactive hyperpolarized agents HP001 (bis-1,1-(hydroxymethyl)-[1-13C]cyclopropane-d8) and urea enable a new type of perfusion magnetic resonance imaging based on a direct signal source that is background-free. The addition of perfusion information to metabolic information obtained...... (T1=95 s ex vivo, 32 s in vivo at 3 T) using a pulse sequence with balanced steady-state free precession and ramped flip angle over time for efficient utilization of the hyperpolarized magnetization and three-dimensional echo-planar spectroscopic imaging of urea copolarized with [1-13C...... of separate dynamic HP001 imaging and copolarized pyruvate/urea imaging were compared. A strong and significant correlation (R=0.73, P=.02) detected between the urea and HP001 data confirmed the value of copolarizing urea with pyruvate for simultaneous assessment of perfusion and metabolism....

Use of potassium-42 in the study of kidney functioning

International Nuclear Information System (INIS)

Morel, F.; Guinnebault, M.

1959-01-01

Following an intravenous injection of potassium-42 as indicator, an analysis of the specific activity vs. time curve in arterial plasma, in venous plasma efferent from the kidney, in urine and in various regions of the kidney of rabbits reveals that: 1) The turnover rate of potassium in the cortex cells (proximal and distal convoluted tubes) is very large, being limited only by renal blood flow. 2) The turnover rate of potassium in deep regions (Henle loops and collector tubules) is much smaller. 3) Potassium in the urine comes from cells of the convoluted tubes and not from cells of Henle loops, collector ducts, or glomerular filtrate. 4) Any potassium filtered at the level of the glomerules would be entirely reabsorbed at the level of the proximal tube, while total potassium in the urine results from a process of excretion by cells of the distal tube. These results are comparable with the assumption that the movement of potassium between interstitial medium and convoluted tube cells results from entirely passive processes. (author) [fr

Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells

Directory of Open Access Journals (Sweden)

Giorgio Grasselli

2016-03-01

Full Text Available The plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the cerebellar nuclei by generating a characteristic spike burst-pause sequence upon synaptic activation. Using patch-clamp recordings from mouse Purkinje cells, we find that depolarization-triggered intrinsic plasticity enhances spike firing and shortens the duration of spike pauses. Pause plasticity is absent from mice lacking SK2-type potassium channels (SK2−/− mice and in occlusion experiments using the SK channel blocker apamin, while apamin wash-in mimics pause reduction. Our findings demonstrate that spike pauses can be regulated through an activity-dependent, exclusively non-synaptic, SK2 channel-dependent mechanism and suggest that pause plasticity—by altering the Purkinje cell output—may be crucial to cerebellar information storage and learning.

Facilitated Anion Transport Induces Hyperpolarization of the Cell Membrane That Triggers Differentiation and Cell Death in Cancer Stem Cells.

Science.gov (United States)

Soto-Cerrato, Vanessa; Manuel-Manresa, Pilar; Hernando, Elsa; Calabuig-Fariñas, Silvia; Martínez-Romero, Alicia; Fernández-Dueñas, Víctor; Sahlholm, Kristoffer; Knöpfel, Thomas; García-Valverde, María; Rodilla, Ananda M; Jantus-Lewintre, Eloisa; Farràs, Rosa; Ciruela, Francisco; Pérez-Tomás, Ricardo; Quesada, Roberto

2015-12-23

Facilitated anion transport potentially represents a powerful tool to modulate various cellular functions. However, research into the biological effects of small molecule anionophores is still at an early stage. Here we have used two potent anionophore molecules inspired in the structure of marine metabolites tambjamines to gain insight into the effect induced by these compounds at the cellular level. We show how active anionophores, capable of facilitating the transmembrane transport of chloride and bicarbonate in model phospholipid liposomes, induce acidification of the cytosol and hyperpolarization of plasma cell membranes. We demonstrate how this combined effect can be used against cancer stem cells (CSCs). Hyperpolarization of cell membrane induces cell differentiation and loss of stemness of CSCs leading to effective elimination of this cancer cell subpopulation.

Activation-Dependent Rapid Postsynaptic Clustering of Glycine Receptors in Mature Spinal Cord Neurons

Science.gov (United States)

Eto, Kei; Murakoshi, Hideji; Watanabe, Miho; Hirata, Hiromi; Moorhouse, Andrew J.; Ishibashi, Hitoshi

2017-01-01

Abstract Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo. While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development. However, GlyR activation induces hyperpolarization after the first postnatal week, and little is known whether and how presynaptically released glycine regulates postsynaptic receptors in a depolarization-independent manner in mature developmental stage. Here we developed spinal cord neuronal culture of rodents using chronic strychnine application to investigate whether initial activation of GlyRs in mature stage could change postsynaptic localization of GlyRs. Immunocytochemical analyses demonstrate that chronic blockade of GlyR activation until mature developmental stage resulted in smaller clusters of postsynaptic GlyRs that could be enlarged upon receptor activation for 1 h in the mature stage. Furthermore, live cell-imaging techniques show that GlyR activation decreases its lateral diffusion at synapses, and this phenomenon is dependent on PKC, but neither Ca2+ nor CaMKII activity. These results suggest that the GlyR activation can regulate receptor diffusion and cluster size at inhibitory synapses in mature stage, providing not only new insights into the postsynaptic mechanism of shifting inhibitory neurotransmission but also the inhibitory synaptic plasticity in mature nervous system. PMID:28197549

Hyperpolarized 13C MR Markers of Renal Tumor Aggressiveness

Science.gov (United States)

2015-12-01

production in the presence of oxygen (11, 12). Increased glycolysis facilitates the uptake and incorporation of nutrients and biomass needed for cell... shell coil; (d) Hyperpolarized lactate images overlaid on T2 weighted anatomical images, clearly depicting the tumor voxels (Figure 5). As shown in

Hyperpolarized C-13 MRS Cardiac Metabolism Studies in Pigs

DEFF Research Database (Denmark)

Giovannetti, G.; Hartwig, V.; Frijia, F.

2012-01-01

Cardiac metabolism assessment with hyperpolarized 13C magnetic resonance spectroscopy in pig models requires the design of dedicated coils capable of providing large field of view with high signal-to-noise ratio (SNR) data. This work presents a comparison between a commercial 13C quadrature...

Estimation of potassium concentration in coconut water by beta radioactivity measurement

International Nuclear Information System (INIS)

Reddy, P.J.; Narayani, K.; Bhade, S.P.D.; Anilkumar, S.; Kolekar, R.V.; Singh, Rajvir; Pradeepkumar, K.S.

2014-01-01

Potassium is widely distributed in soil, in all vegetable, fruits and animal tissues. Approximately half the radioactivity found in humans comes from 40 K. Potassium is an essential element in our diet since it is required for proper nerve and muscle function, as well as for maintaining the fluid balance of cells and heart rhythm. Potassium can enter the body mainly consuming fruits, vegetables and food. Tender coconut water is consumed widely as natural refreshing drink which is rich in potassium. The simple way to determine 40 K activity is by gamma ray spectrometry. However, the low abundance of this gamma photon makes the technique less sensitive compared to gross beta measurement. Many analytical methods are reported for potassium estimation which is time consuming and destructive in nature. A unique way to estimate 40 K by beta activity is by Cerenkov Counting technique using Liquid Scintillation Analyzer. Also much lower detection limit is achieved, allowing for greater precision. In this work, we have compared two methods to arrive at the potassium concentration in tender and matured coconut water by measuring 40 K. One is non-scintillator method based on measurement of the Cerenkov radiation generated from the high-energy β of 40 K. The second method is based on beta activity measurement using low background Gas flow counter

Imaging Human Brain Perfusion with Inhaled Hyperpolarized 129Xe MR Imaging.

Science.gov (United States)

Rao, Madhwesha R; Stewart, Neil J; Griffiths, Paul D; Norquay, Graham; Wild, Jim M

2018-02-01

Purpose To evaluate the feasibility of directly imaging perfusion of human brain tissue by using magnetic resonance (MR) imaging with inhaled hyperpolarized xenon 129 ( 129 Xe). Materials and Methods In vivo imaging with 129 Xe was performed in three healthy participants. The combination of a high-yield spin-exchange optical pumping 129 Xe polarizer, custom-built radiofrequency coils, and an optimized gradient-echo MR imaging protocol was used to achieve signal sensitivity sufficient to directly image hyperpolarized 129 Xe dissolved in the human brain. Conventional T1-weighted proton (hydrogen 1 [ 1 H]) images and perfusion images by using arterial spin labeling were obtained for comparison. Results Images of 129 Xe uptake were obtained with a signal-to-noise ratio of 31 ± 9 and demonstrated structural similarities to the gray matter distribution on conventional T1-weighted 1 H images and to perfusion images from arterial spin labeling. Conclusion Hyperpolarized 129 Xe MR imaging is an injection-free means of imaging the perfusion of cerebral tissue. The proposed method images the uptake of inhaled xenon gas to the extravascular brain tissue compartment across the intact blood-brain barrier. This level of sensitivity is not readily available with contemporary MR imaging methods. © RSNA, 2017.

Modulation of Potassium Channel Activity in the Balance of ROS and ATP Production by Durum Wheat Mitochondria - An amazing defence tool against hyperosmotic stress

Directory of Open Access Journals (Sweden)

Daniela eTrono

2015-12-01

Full Text Available In plants, the existence of a mitochondrial potassium channel was firstly demonstrated about fifteen years ago in durum wheat as an ATP-dependent potassium channel (PmitoKATP. Since then, both properties of the original PmitoKATP and occurrence of different mitochondrial potassium channels in a number of plant species (monocotyledonous and dicotyledonous and tissues/organs (etiolated and green have been shown. Here, an overview of the current knowledge is reported; in particular, the issue of PmitoKATP physiological modulation is addressed. Similarities and differences with other potassium channels, as well as possible cross-regulation with other mitochondrial proteins (Plant Uncoupling Protein, Alternative Oxidase, Plant Inner Membrane Anion Channel are also described. PmitoKATP is inhibited by ATP and activated by superoxide anion, as well as by free fatty acids (FFAs and acyl-CoAs. Interestingly, channel activation increases electrophoretic potassium uptake across the inner membrane towards the matrix, so collapsing membrane potential (ΔΨ, the main component of the protonmotive force (Δp in plant mitochondria; moreover, cooperation between PmitoKATP and the K+/H+ antiporter allows a potassium cycle able to dissipate also ΔpH. Interestingly, ΔΨ collapse matches with an active control of mitochondrial reactive oxygen species (ROS production. Fully open channel is able to lower superoxide anion up to 35-fold compared to a condition of ATP-inhibited channel. On the other hand, ΔΨ collapse by PmitoKATP was unexpectedly found to not affect ATP synthesis via oxidative phosphorylation. This may probably occur by means of a controlled collapse due to ATP inhibition of PmitoKATP; this brake to the channel activity may allow a loss of the bulk phase Δp, but may preserve a non-classically detectable localized driving force for ATP synthesis. This ability may become crucial under environmental/oxidative stress. In particular, under moderate

Simultaneous hyperpolarized 13C-pyruvate MRI and 18F-FDG-PET in cancer (hyperPET)

DEFF Research Database (Denmark)

Gutte, Henrik; Hansen, Adam E.; Henriksen, Sarah T.

2015-01-01

named this concept hyper PET. Intravenous injection of the hyperpolarized 13C-pyruvate results in an increase of 13C-lactate, 13C-alanine and 13CCO2 (13C-HCO3) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization (DNP) and use......In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and 18F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We have...... of 13C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of 13C-pyruvate to 13C-lactate. In this study, we combined it with 18F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified local recurrence...

Catalytic activity of supported silver and potassium salts of tungstophosphoric acid in dehydration of ethanol

International Nuclear Information System (INIS)

Haber, J.; Matachowski, L.; Pamin, K.; Napruszewska, B.

2002-01-01

Potassium and silver salts of tungstophosphoric acid (HPW) have been supported on silica. Two series of potassium and silver salts of tungstophosphoric acid K x H 3-x PW 12 O 40 and Ag x H 3-x PW 12 O 40 where x = 1;2;3 supported on silica were prepared using incipient wetness method. In a typical synthesis, the heteropolyacid which after deposition on silica was washed with water to remove the part of heteropolyacid not bound to the support was reacted with silver or potassium salt. The vapor-phase dehydration of ethanol was employed as a test reaction. All the catalytic tests were carried out in a conventional flow type reactor, under atmospheric pressure, in the temperature range 125-500 o C. The results of these studies were used to explain the differences between the catalytic activities of heteropolysalts of potassium and silver supported on silica. (author)

Firing patterns and synchronization in nonsynaptic epileptiform activity: the effect of gap junctions modulated by potassium accumulation

International Nuclear Information System (INIS)

Santos, D O C; Dickman, R; Rodrigues, A M; De Almeida, A C G

2009-01-01

Several lines of evidence point to the modification of firing patterns and of synchronization due to gap junctions (GJs) as having a role in the establishment of epileptiform activity (EA). However, previous studies consider GJs as ohmic resistors, ignoring the effects of intense variations in ionic concentration known to occur during seizures. In addition to GJs, extracellular potassium is regarded as a further important factor involved in seizure initiation and sustainment. To analyze how these two mechanisms act together to shape firing and synchronization, we use a detailed computational model for in vitro high-K + and low-Ca 2+ nonsynaptic EA. The model permits us to explore the modulation of electrotonic interactions under ionic concentration changes caused by electrodiffusion in the extracellular space, altered by tortuosity. In addition, we investigate the special case of null GJ current. Increased electrotonic interaction alters bursts and action potential frequencies, favoring synchronization. The particularities of pattern changes depend on the tortuosity and array size. Extracellular potassium accumulation alone modifies firing and synchronization when the GJ coupling is null

Time-dependent changes in rat lymphocyte activity in response to isolation

International Nuclear Information System (INIS)

Jessop, J.J.; Bayer, B.M.

1986-01-01

The authors have found that isolation of rats, previously adapted to group-housing conditions, resulted in time-dependent changes in mitogenic and cytolytic responses of lymphocytes. A depression (40-60%) of the uptake of 3 H-thymidine by splenic and blood lymphocytes stimulated with either phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was observed during the first 48 hours after transfer of the animals to individual cages. Within 4 days the mitogenic response increased and was comparable to that of animals which had been continuously group-housed. The response continued to increase and by 10 days was enhanced by 2 to 4 fold and remained elevated for at least 8 weeks. Similar changes in activity were observed with both splenic and blood lymphocytes, however, thymic lymphocytes taken from isolated animals demonstrated no change in reactivity to PHA. As with mitogenic responses, the cytolytic activity of splenic lymphocytes was also depressed during the initial days of isolation and as isolation continued, the activity returned to normal and was significantly enhanced (80%) within 5 weeks. These data show that changes in lymphocyte activity are dependent on the duration of exposure to isolated housing conditions and may be a part of the acute, adaptive and chronic phases of the response of rats to the stress of isolation

The NH2 terminus regulates voltage-dependent gating of CALHM ion channels.

Science.gov (United States)

Tanis, Jessica E; Ma, Zhongming; Foskett, J Kevin

2017-08-01

Calcium homeostasis modulator protein-1 (CALHM1) and its Caenorhabditis elegans (ce) homolog, CLHM-1, belong to a new family of physiologically important ion channels that are regulated by voltage and extracellular Ca 2+ (Ca 2+ o ) but lack a canonical voltage-sensing domain. Consequently, the intrinsic voltage-dependent gating mechanisms for CALHM channels are unknown. Here, we performed voltage-clamp experiments on ceCLHM-1 chimeric, deletion, insertion, and point mutants to assess the role of the NH 2 terminus (NT) in CALHM channel gating. Analyses of chimeric channels in which the ceCLHM-1 and human (h)CALHM1 NH 2 termini were interchanged showed that the hCALHM1 NT destabilized channel-closed states, whereas the ceCLHM-1 NT had a stabilizing effect. In the absence of Ca 2+ o , deletion of up to eight amino acids from the ceCLHM-1 NT caused a hyperpolarizing shift in the conductance-voltage relationship with little effect on voltage-dependent slope. However, deletion of nine or more amino acids decreased voltage dependence and induced a residual conductance at hyperpolarized voltages. Insertion of amino acids into the NH 2 -terminal helix also decreased voltage dependence but did not prevent channel closure. Mutation of ceCLHM-1 valine 9 and glutamine 13 altered half-maximal activation and voltage dependence, respectively, in 0 Ca 2+ In 2 mM Ca 2+ o , ceCLHM-1 NH 2 -terminal deletion and point mutant channels closed completely at hyperpolarized voltages with apparent affinity for Ca 2+ o indistinguishable from wild-type ceCLHM-1, although the ceCLHM-1 valine 9 mutant exhibited an altered conductance-voltage relationship and kinetics. We conclude that the NT plays critical roles modulating voltage dependence and stabilizing the closed states of CALHM channels. Copyright © 2017 the American Physiological Society.

A new model for the estimation of time of death from vitreous potassium levels corrected for age and temperature.

Science.gov (United States)

Zilg, B; Bernard, S; Alkass, K; Berg, S; Druid, H

2015-09-01

Analysis of potassium concentration in the vitreous fluid of the eye is frequently used by forensic pathologists to estimate the postmortem interval (PMI), particularly when other methods commonly used in the early phase of an investigation can no longer be applied. The postmortem rise in vitreous potassium has been recognized for several decades and is readily explained by a diffusion of potassium from surrounding cells into the vitreous fluid. However, there is no consensus regarding the mathematical equation that best describes this increase. The existing models assume a linear increase, but different slopes and starting points have been proposed. In this study, vitreous potassium levels, and a number of factors that may influence these levels, were examined in 462 cases with known postmortem intervals that ranged from 2h to 17 days. We found that the postmortem rise in potassium followed a non-linear curve and that decedent age and ambient temperature influenced the variability by 16% and 5%, respectively. A long duration of agony and a high alcohol level at the time of death contributed less than 1% variability, and evaluation of additional possible factors revealed no detectable impact on the rise of vitreous potassium. Two equations were subsequently generated, one that represents the best fit of the potassium concentrations alone, and a second that represents potassium concentrations with correction for decedent age and/or ambient temperature. The former was associated with narrow confidence intervals in the early postmortem phase, but the intervals gradually increased with longer PMIs. For the latter equation, the confidence intervals were reduced at all PMIs. Therefore, the model that best describes the observed postmortem rise in vitreous potassium levels includes potassium concentration, decedent age, and ambient temperature. Furthermore, the precision of these equations, particularly for long PMIs, is expected to gradually improve by adjusting the

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

Directory of Open Access Journals (Sweden)

Dong-Hai Liu

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

Novel time-dependent vascular actions of {delta}{sup 9}-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma

Energy Technology Data Exchange (ETDEWEB)

O' Sullivan, Saoirse E [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Tarling, Elizabeth J [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Bennett, Andrew J [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Kendall, David A [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Randall, Michael D [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom)

2005-11-25

Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, {delta}{sup 9}-tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPAR{gamma}). In vitro, THC (10 {mu}M) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPAR{gamma} agonist rosiglitazone and was inhibited by the PPAR{gamma} antagonist GW9662 (1 {mu}M), but not the cannabinoid CB{sub 1} receptor antagonist AM251 (1 {mu}M). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPAR{gamma}, transiently expressed in combination with retinoid X receptor {alpha} and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 {mu}M). In vitro incubation with THC (1 or 10 {mu}M, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPAR{gamma} ligands. The present results provide strong evidence that THC is a PPAR{gamma} ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of cannabis may be mediated by nuclear receptors.

Effect of Timing of Potassium Application on Millet (Setaria italica Yield and Grain Protein Content in Different Irrigation Regimes

Directory of Open Access Journals (Sweden)

A. Hayati

2011-05-01

Full Text Available The research on reducing the water consumption in conventional cropping system is one of the important strategies to improve the water use efficiency in agriculture. In order to investigate the effect of time of potassium application under different irrigation regimes on millet grain yield and protein percent, a field experiment was carried out in Agricultural Research Center of Yasuj, Iran, in 2009. The experiment was conducted as split plot design in a randomized complete blocks design with 3 replications. Irrigation regime included 7, 14 and 21-day intervals as main factor and sub-plots included time of potassium fertilizer application in four stages: planting, tillering, stem development and flowering. The results showed that the effect of irrigation interval was significant on 1000-seed weight, grain and biological yield, number of grains per spike, harvest index, protein content, and chlorophyll a, b and total of leaves. By increasing the irrigation interval, all the above-mentioned traits decreased, except the protein percent that increased. The 1000-seed weight, grain and biological yield, harvest index and protein content were affected significantly by the time of potassium application. Maximum grain yield was obtained by interaction of 7- day irrigation interval and potassium application at the stem development stage. Maximum grain protein content was measured in potassium application at flowering stage. In general, increasing the irrigation interval, and subsequent water stress, reduced plant growth and yield components. Application of potassium fertilizer at early growth stages increased yield and yield components, while in reproductive stages increased seed quality.

Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones

Science.gov (United States)

Sirois, Jay E; Lynch, Carl; Bayliss, Douglas A

2002-01-01

Neurotransmitters and volatile anaesthetics have opposing effects on motoneuronal excitability which appear to reflect contrasting modulation of two types of subthreshold currents. Neurotransmitters increase motoneuronal excitability by inhibiting TWIK-related acid-sensitive K+ channels (TASK) and shifting activation of a hyperpolarization-activated cationic current (Ih) to more depolarized potentials; on the other hand, anaesthetics decrease excitability by activating a TASK-like current and inducing a hyperpolarizing shift in Ih activation. Here, we used whole-cell recording from motoneurones in brainstem slices to test if neurotransmitters (serotonin (5-HT) and noradrenaline (NA)) and an anaesthetic (halothane) indeed compete for modulation of the same ion channels - and we determined which prevails. When applied together under current clamp conditions, 5-HT reversed anaesthetic-induced membrane hyperpolarization and increased motoneuronal excitability. Under voltage clamp conditions, 5-HT and NA overcame most, but not all, of the halothane-induced current. When Ih was blocked with ZD 7288, the neurotransmitters completely inhibited the K+ current activated by halothane; the halothane-sensitive neurotransmitter current reversed at the equilibrium potential for potassium (EK) and displayed properties expected of acid-sensitive, open-rectifier TASK channels. To characterize modulation of Ih in relative isolation, effects of 5-HT and halothane were examined in acidified bath solutions that blocked TASK channels. Under these conditions, 5-HT and halothane each caused their characteristic shift in voltage-dependent gating of Ih. When tested concurrently, however, halothane decreased the neurotransmitter-induced depolarizing shift in Ih activation. Thus, halothane and neurotransmitters converge on TASK and Ih channels with opposite effects; transmitter action prevailed over anaesthetic effects on TASK channels, but not over effects on Ih. These data suggest that

Genetic variation in Hyperpolarization-activated cyclic nucleotide-gated (HCN channels and its relationship with neuroticism, cognition and risk of depression

Directory of Open Access Journals (Sweden)

Andrew Mark Mcintosh

2012-07-01

Full Text Available Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are encoded by four genes (HCN1-4 and, through activation by cyclic AMP (cAMP, represent a point of convergence for several psychosis risk genes. On the basis of positive preliminary data, we sought to test whether genetic variation in HCN1-4 conferred risk of depression or cognitive impairment in the Generation Scotland: Scottish Family Health Study. HCN1, HCN2, HCN3 and HCN4 were genotyped for 43 haplotype-tagging SNPs and tested for association with DSM-IV depression, neuroticism and a battery of cognitive tests assessing cognitive ability, memory, verbal fluency and psychomotor performance. No association was found between any HCN channel gene SNP and risk of depression, neuroticism or on any cognitive measure. The current study does not support a genetic role for HCN channels in conferring risk of depression or cognitive impairment in human subjects within the Scottish population.

Loss of Sodium-Activated Potassium Channel Slack and FMRP Differentially Affect Social Behavior in Mice.

Science.gov (United States)

Bausch, Anne E; Ehinger, Rebekka; Straubinger, Julia; Zerfass, Patrick; Nann, Yvette; Lukowski, Robert

2018-05-31

The sodium-activated potassium channel Slack (Slo2.2) is widely expressed in central and peripheral neurons where it is supposed to shape firing properties important for neuronal excitability. Slack activity is enhanced by interaction with the Fragile-X-Mental-Retardation-Protein (FMRP) and loss of FMRP leads to decreased sodium-activated potassium currents in medial nucleus of the trapezoid body neurons of the Fmr1-knockout (KO) mouse representing a mouse model of the human Fragile-X-Syndrome (FXS) and autism. Autism is a frequent comorbidity of FXS, but it is unclear whether Slack is involved in autistic or related conditions of FXS in vivo. By applying a wide range of behavioral tests, we compared social and autism-related behaviors in Slack- and FMRP-deficient mice. In our hands, as expected, FMRP-deficiency causes autism-related behavioral changes in nesting and in a marble-burying test. In contrast, Slack-deficient males exhibited specific abnormalities in sociability in direct and indirect social interaction tests. Hence, we show for the first time that a proper Slack channel function is mandatory for normal social behavior in mice. Nevertheless, as deficits in social behaviors seem to occur independently from each other in FMRP and Slack null mutants, we conclude that Slack is not involved in the autistic phenotype of FMRP KO mice. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Nanodiamond-enhanced MRI via in situ hyperpolarization

Science.gov (United States)

Waddington, David E. J.; Sarracanie, Mathieu; Zhang, Huiliang; Salameh, Najat; Glenn, David R.; Rej, Ewa; Gaebel, Torsten; Boele, Thomas; Walsworth, Ronald L.; Reilly, David J.; Rosen, Matthew S.

2017-04-01

Nanodiamonds are of interest as nontoxic substrates for targeted drug delivery and as highly biostable fluorescent markers for cellular tracking. Beyond optical techniques, however, options for noninvasive imaging of nanodiamonds in vivo are severely limited. Here, we demonstrate that the Overhauser effect, a proton-electron polarization transfer technique, can enable high-contrast magnetic resonance imaging (MRI) of nanodiamonds in water at room temperature and ultra-low magnetic field. The technique transfers spin polarization from paramagnetic impurities at nanodiamond surfaces to 1H spins in the surrounding water solution, creating MRI contrast on-demand. We examine the conditions required for maximum enhancement as well as the ultimate sensitivity of the technique. The ability to perform continuous in situ hyperpolarization via the Overhauser mechanism, in combination with the excellent in vivo stability of nanodiamond, raises the possibility of performing noninvasive in vivo tracking of nanodiamond over indefinitely long periods of time.

Population coherent control of Rydberg potassium atom via adiabatic passage

International Nuclear Information System (INIS)

Jiang Li-Juan; Zhang Xian-Zhou; Jia Guang-Rui; Zhang Yong-Hui; Xia Li-Hua

2013-01-01

The time-dependent multilevel approach (TDMA) and B-spline expansion technique are used to study the coherent population transfer between the quantum states of a potassium atom by a single frequency-chirped microwave pulse. The Rydberg potassium atom energy levels of n = 6–15, l = 0–5 states in zero field are calculated and the results are in good agreement with other theoretical values. The time evolutions of the population transfer of the six states from n = 70 to n = 75 in different microwave fields are obtained. The results show that the coherent control of the population transfer from the lower states to the higher ones can be accomplished by optimizing the microwave pulse parameters. (atomic and molecular physics)

MicroRNA-Mediated Downregulation of the Potassium Channel Kv4.2 Contributes to Seizure Onset

Directory of Open Access Journals (Sweden)

Christina Gross

2016-09-01

Full Text Available Seizures are bursts of excessive synchronized neuronal activity, suggesting that mechanisms controlling brain excitability are compromised. The voltage-gated potassium channel Kv4.2, a major mediator of hyperpolarizing A-type currents in the brain, is a crucial regulator of neuronal excitability. Kv4.2 expression levels are reduced following seizures and in epilepsy, but the underlying mechanisms remain unclear. Here, we report that Kv4.2 mRNA is recruited to the RNA-induced silencing complex shortly after status epilepticus in mice and after kainic acid treatment of hippocampal neurons, coincident with reduction of Kv4.2 protein. We show that the microRNA miR-324-5p inhibits Kv4.2 protein expression and that antagonizing miR-324-5p is neuroprotective and seizure suppressive. MiR-324-5p inhibition also blocks kainic-acid-induced reduction of Kv4.2 protein in vitro and in vivo and delays kainic-acid-induced seizure onset in wild-type but not in Kcnd2 knockout mice. These results reveal an important role for miR-324-5p-mediated silencing of Kv4.2 in seizure onset.

Characterization and optimization of the visualization performance of continuous flow overhauser DNP hyperpolarized water MRI: Inversion recovery approach.

Science.gov (United States)

Terekhov, Maxim; Krummenacker, Jan; Denysenkov, Vasyl; Gerz, Kathrin; Prisner, Thomas; Schreiber, Laura Maria

2016-03-01

Overhauser dynamic nuclear polarization (DNP) allows the production of liquid hyperpolarized substrate inside the MRI magnet bore as well as its administration in continuous flow mode to acquire MR images with enhanced signal-to-noise ratio. We implemented inversion recovery preparation in order to improve contrast-to-noise ratio and to quantify the overall imaging performance of Overhauser DNP-enhanced MRI. The negative enhancement created by DNP in combination with inversion recovery (IR) preparation allows canceling selectively the signal originated from Boltzmann magnetization and visualizing only hyperpolarized fluid. The theoretical model describing gain of MR image intensity produced by steady-state continuous flow DNP hyperpolarized magnetization was established and proved experimentally. A precise quantification of signal originated purely from DNP hyperpolarization was achieved. A temperature effect on longitudinal relaxation had to be taken into account to fit experimental results with numerical prediction. Using properly adjusted IR preparation, the complete zeroing of thermal background magnetization was achieved, providing an essential increase of contrast-to-noise ratio of DNP-hyperpolarized water images. To quantify and optimize the steady-state conditions for MRI with continuous flow DNP, an approach similar to that incorporating transient-state thermal magnetization equilibrium in spoiled fast field echo imaging sequences can be used. © 2015 Wiley Periodicals, Inc.

Fluconazole treatment hyperpolarizes the plasma membrane of Candida cells

Czech Academy of Sciences Publication Activity Database

Elicharová, Hana; Sychrová, Hana

2013-01-01

Roč. 51, č. 8 (2013), s. 785-798 ISSN 1369-3786 R&D Projects: GA ČR GAP302/12/1151 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : drug resistance * fluconazol * yeast * hyperpolarization Subject RIV: EE - Microbiology, Virology Impact factor: 2.261, year: 2013

Contribution of large-sized primary sensory neuronal sensitization to mechanical allodynia by upregulation of hyperpolarization-activated cyclic nucleotide gated channels via cyclooxygenase 1 cascade.

Science.gov (United States)

Sun, Wei; Yang, Fei; Wang, Yan; Fu, Han; Yang, Yan; Li, Chun-Li; Wang, Xiao-Liang; Lin, Qing; Chen, Jun

2017-02-01

Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated. Behaviorally, it was found that mechanical allodynia was still evoked by BV injection in rats in which the transient receptor potential vanilloid 1-positive DRG neurons were chemically deleted. Electrophysiologically, in vitro patch clamp recordings of large-sized neurons showed hyperexcitability in these neurons. Interestingly, the firing pattern of these neurons was changed from phasic to tonic under BV-inflamed state. It has been suggested that hyperpolarization-activated cyclic nucleotide gated channels (HCN) expressed in large-sized DRG neurons contribute importantly to repeatedly firing. So we examined the roles of HCNs in BV-induced mechanical allodynia. Consistent with the overexpression of HCN1/2 detected by immunofluorescence, HCNs-mediated hyperpolarization activated cation current (I h ) was significantly increased in the BV treated samples. Pharmacological experiments demonstrated that the hyperexcitability and upregulation of I h in large-sized neurons were mediated by cyclooxygenase-1 (COX-1)-prostaglandin E2 pathway. This is evident by the fact that the COX-1 inhibitor significantly attenuated the BV-induced mechanical allodynia. These results suggest that BV can excite the large-sized DRG neurons at least in part by increasing I h through activation of COX-1. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Novel Time-Dependent CENP-E Inhibitor with Potent Antitumor Activity.

Directory of Open Access Journals (Sweden)

Akihiro Ohashi

Full Text Available Centromere-associated protein E (CENP-E regulates both chromosome congression and the spindle assembly checkpoint (SAC during mitosis. The loss of CENP-E function causes chromosome misalignment, leading to SAC activation and apoptosis during prolonged mitotic arrest. Here, we describe the biological and antiproliferative activities of a novel small-molecule inhibitor of CENP-E, Compound-A (Cmpd-A. Cmpd-A inhibits the ATPase activity of the CENP-E motor domain, acting as a time-dependent inhibitor with an ATP-competitive-like behavior. Cmpd-A causes chromosome misalignment on the metaphase plate, leading to prolonged mitotic arrest. Treatment with Cmpd-A induces antiproliferation in multiple cancer cell lines. Furthermore, Cmpd-A exhibits antitumor activity in a nude mouse xenograft model, and this antitumor activity is accompanied by the elevation of phosphohistone H3 levels in tumors. These findings demonstrate the potency of the CENP-E inhibitor Cmpd-A and its potential as an anticancer therapeutic agent.

Extrarenal potassium adaptation: role of skeletal muscle

International Nuclear Information System (INIS)

Blachley, J.D.; Crider, B.P.; Johnson, J.H.

1986-01-01

Following the ingestion of a high-potassium-content diet for only a few days, the plasma potassium of rats rises only modestly in response to a previously lethal dose of potassium salts. This acquired tolerance, termed potassium adaptation, is principally the result of increased capacity to excrete potassium into the urine. However, a substantial portion of the acute potassium dose is not immediately excreted and is apparently translocated into cells. Previous studies have failed to show an increase in the content of potassium of a variety of tissues from such animals. Using 86 Rb as a potassium analogue, we have shown that the skeletal muscle of potassium-adapted rats takes up significantly greater amounts of potassium in vivo in response to an acute challenge than does that of control animals. Furthermore, the same animals exhibit greater efflux of 86 Rb following the termination of the acute infusion. We have also shown that the Na+-K+-ATPase activity and ouabain-binding capacity of skeletal muscle microsomes are increased by the process of potassium adaptation. We conclude that skeletal muscle is an important participant in potassium adaptation and acts to temporarily buffer acute increases in the extracellular concentration of potassium

Delayed rectifier potassium channels are involved in SO2 derivative-induced hippocampal neuronal injury.

Science.gov (United States)

Li, Guangke; Sang, Nan

2009-01-01

Recent studies implicate the possible neurotoxicity of SO(2), however, its mechanisms remain unclear. In the present study, we investigated SO(2) derivative-induced effect on delayed rectifier potassium channels (I(K)) and cellular death/apoptosis in primary cultured hippocampal neurons. The results demonstrate that SO(2) derivatives (NaHSO(3) and Na(2)SO(3), 3:1M/M) effectively augmented I(K) and promoted the activation of delayed rectifier potassium channels. Also, SO(2) derivatives increased neuronal death percentage and contributed to the formation of DNA ladder in concentration-dependent manners. Interestingly, the neuronal death and DNA ladder formation, caused by SO(2) derivatives, could be attenuated by the delayed rectifier potassium channel blocker (tetraethylammonium, TEA), but not by the transient outward potassium channel blocker (4-aminopyridine, 4-AP). It implies that stimulating delayed rectifier potassium channels were involved in SO(2) derivative-caused hippocampal neuronal insults, and blocking these channels might be one of the possibly clinical treatment for SO(2)-caused neuronal dysfunction.

Reversed synaptic effects of hypocretin and NPY mediated by excitatory GABA-dependent synaptic activity in developing MCH neurons.

Science.gov (United States)

Li, Ying; Xu, Youfen; van den Pol, Anthony N

2013-03-01

In mature neurons, GABA is the primary inhibitory neurotransmitter. In contrast, in developing neurons, GABA exerts excitatory actions, and in some neurons GABA-mediated excitatory synaptic activity is more prevalent than glutamate-mediated excitation. Hypothalamic neuropeptides that modulate cognitive arousal and energy homeostasis, hypocretin/orexin and neuropeptide Y (NPY), evoked reversed effects on synaptic actions that were dependent on presynaptic GABA release onto melanin-concentrating hormone (MCH) neurons. MCH neurons were identified by selective green fluorescent protein (GFP) expression in transgenic mice. In adults, hypocretin increased GABA release leading to reduced excitation. In contrast, in the developing brain as studied here with analysis of miniature excitatory postsynaptic currents, paired-pulse ratios, and evoked potentials, hypocretin acted presynaptically to enhance the excitatory actions of GABA. The ability of hypocretin to enhance GABA release increases inhibition in adult neurons but paradoxically enhances excitation in developing MCH neurons. In contrast, NPY attenuation of GABA release reduced inhibition in mature neurons but enhanced inhibition during development by attenuating GABA excitation. Both hypocretin and NPY also evoked direct actions on developing MCH neurons. Hypocretin excited MCH cells by activating a sodium-calcium exchanger and by reducing potassium currents; NPY reduced activity by increasing an inwardly rectifying potassium current. These data for the first time show that both hypocretin and NPY receptors are functional presynaptically during early postnatal hypothalamic development and that both neuropeptides modulate GABA actions during development with a valence of enhanced excitation or inhibition opposite to that of the adult state, potentially allowing neuropeptide modulation of use-dependent synapse stabilization.

Analysis of Cancer Metabolism by Imaging Hyperpolarized Nuclei: Prospects for Translation to Clinical Research

Directory of Open Access Journals (Sweden)

John Kurhanewicz

2011-02-01

Full Text Available A major challenge in cancer biology is to monitor and understand cancer metabolism in vivo with the goal of improved diagnosis and perhaps therapy. Because of the complexity of biochemical pathways, tracer methods are required for detecting specific enzyme-catalyzed reactions. Stable isotopes such as 13C or 15N with detection by nuclear magnetic resonance provide the necessary information about tissue biochemistry, but the crucial metabolites are present in low concentration and therefore are beyond the detection threshold of traditional magnetic resonance methods. A solution is to improve sensitivity by a factor of 10,000 or more by temporarily redistributing the populations of nuclear spins in a magnetic field, a process termed hyperpolarization. Although this effect is short-lived, hyperpolarized molecules can be generated in an aqueous solution and infused in vivo where metabolism generates products that can be imaged. This discovery lifts the primary constraint on magnetic resonance imaging for monitoring metabolism—poor sensitivity—while preserving the advantage of biochemical information. The purpose of this report was to briefly summarize the known abnormalities in cancer metabolism, the value and limitations of current imaging methods for metabolism, and the principles of hyperpolarization. Recent preclinical applications are described. Hyperpolarization technology is still in its infancy, and current polarizer equipment and methods are suboptimal. Nevertheless, there are no fundamental barriers to rapid translation of this exciting technology to clinical research and perhaps clinical care.

Changes by short-term hypoxia in the membrane properties of pyramidal cells and the levels of purine and pyrimidine nucleotides in slices of rat neocortex; effects of agonists and antagonists of ATP-dependent potassium channels.

Science.gov (United States)

Pissarek, M; Garcia de Arriba, S; Schäfer, M; Sieler, D; Nieber, K; Illes, P

1998-10-01

In a first series of experiments, intracellular recordings were made from pyramidal cells in layers II-III of the rat primary somatosensory cortex. Superfusion of the brain slice preparations with hypoxic medium (replacement of 95%O2-5%CO2 with 95%N2-5%CO2) for up to 30 min led to a time-dependent depolarization (HD) without a major change in input resistance. Short periods of hypoxia (5 min) induced reproducible depolarizations which were concentration-dependently depressed by an agonist of ATP-dependent potassium (K(ATP)) channels, diazoxide (3-300 microM). The effect of 30 but not 300 microM diazoxide was reversed by washout. Tolbutamide (300 microM), an antagonist of K(ATP) channels, did not alter the HD when given alone. It did, however, abolish the inhibitory effect of diazoxide (30 microM) on the HD. Neither diazoxide (3-300 microM) nor tolbutamide (300 microM) influenced the membrane potential or the apparent input resistance of the neocortical pyramidal cells. Current-voltage (I-V) curves constructed at a membrane potential of -90 mV by injecting both de- and hyperpolarizing current pulses were not altered by diazoxide (30 microM) or tolbutamide (300 microM). Moreover, normoxic and hypoxic I-V curves did not cross each other, excluding a reversal of the HD at any membrane potential between -130 and -50 mV. The hypoxia-induced change of the I-V relation was the same both in the absence and presence of tolbutamide (300 microM). In a second series of experiments, nucleoside di- and triphosphates separated with anion exchange HPLC were measured in the neocortical slices. After 5 min of hypoxia, levels of nucleoside triphosphates declined by 29% (GTP), 34% (ATP), 44% (UTP) and 58% (CTP). By contrast, the levels of nucleoside diphosphates either did not change (UDP) or increased by 13% (GDP) and 40% (ADP). In slices subjected to 30 min of hypoxia the triphosphate levels continued to decrease, while the levels of GDP and ADP returned to control values. The tri

Single Machine Problem with Multi-Rate-Modifying Activities under a Time-Dependent Deterioration

Directory of Open Access Journals (Sweden)

M. Huang

2013-01-01

Full Text Available The single machine scheduling problem with multi-rate-modifying activities under a time-dependent deterioration to minimize makespan is studied. After examining the characteristics of the problem, a number of properties and a lower bound are proposed. A branch and bound algorithm and a heuristic algorithm are used in the solution, and two special cases are also examined. The computational experiments show that, for the situation with a rate-modifying activity, the proposed branch and bound algorithm can solve situations with 50 jobs within a reasonable time, and the heuristic algorithm can obtain the near-optimal solution with an error percentage less than 0.053 in a very short time. In situations with multi-rate-modifying activities, the proposed branch and bound algorithm can solve the case with 15 jobs within a reasonable time, and the heuristic algorithm can obtain the near-optimal with an error percentage less than 0.070 in a very short time. The branch and bound algorithm and the heuristic algorithm are both shown to be efficient and effective.

Chloride is essential for contraction of afferent arterioles after agonists and potassium

DEFF Research Database (Denmark)

Jensen, B L; Ellekvist, Peter; Skøtt, O

1997-01-01

to norepinephrine, angiotensin II (ANG II), and potassium were measured after chloride depletion and compared with controls. Chloride depletion did not change arteriolar diameters, but the response to norepinephrine was markedly reduced when chloride was substituted with gluconate (n = 6) or isethionate (n = 6......). Reintroduction of chloride fully restored the sensitivity to norepinephrine. Contractions after ANG II and potassium were totally abolished in the absence of chloride (n = 6). In additional experiments (n = 7), the arteriolar contraction to 100 mM potassium was abolished only 1 min after removal of extracellular......A depolarizing chloride efflux has been suggested to activate voltage-dependent calcium channels in renal afferent arteriolar smooth muscle cells in response to vasoconstrictors. To test this proposal, rabbit afferent arterioles were microperfused, and the contractile dose responses...

40K activities and potassium concentrations in tobacco samples of Mexican cigarettes

International Nuclear Information System (INIS)

Martinez, T.; Navarrete, M.; Cabrera, L.; Ramos, A.; Vazquez, K.; Juarez, F.

2007-01-01

Nine brands of tobacco cigarettes manufactured and distributed in the Mexican market were analyzed by γ-spectrometry to certify their nonartificial radioactive contamination. Since natural occurring radioactive materials (NORM) 40 K, 232 Th, 235 U, and 239 U (and decay products from the latter three nuclides) are the main sources for human radiation exposure, the aim of this work was to determine the activity of 40 K and potassium concentration. Averages of 40 K and potassium concentration were of 1.29 ± 0.18 Bq x g -1 , and 4.0 ± 0.57%. The annual dose equivalents to the whole body from ingestion and inhalation of 26 Bq 40 K were 0.23 μSv and 15.8 μSv, respectively. The corresponding 50 years committed dose equivalents was 0.23 μSv. The total committed dose to the lungs due to inhalation of 40 K in tobacco was 16 μSv. Potassium concentrations obtained in this work were in the same range of those obtained by INAA, so showing that the used technique is acute, reproducible, and accessible to laboratories equipped with low background scintillation detectors. (author)

Ancient Systems of Sodium/Potassium Homeostasis as Predecessors of Membrane Bioenergetics.

Science.gov (United States)

Dibrova, D V; Galperin, M Y; Koonin, E V; Mulkidjanian, A Y

2015-05-01

Cell cytoplasm of archaea, bacteria, and eukaryotes contains substantially more potassium than sodium, and potassium cations are specifically required for many key cellular processes, including protein synthesis. This distinct ionic composition and requirements have been attributed to the emergence of the first cells in potassium-rich habitats. Different, albeit complementary, scenarios have been proposed for the primordial potassium-rich environments based on experimental data and theoretical considerations. Specifically, building on the observation that potassium prevails over sodium in the vapor of inland geothermal systems, we have argued that the first cells could emerge in the pools and puddles at the periphery of primordial anoxic geothermal fields, where the elementary composition of the condensed vapor would resemble the internal milieu of modern cells. Marine and freshwater environments generally contain more sodium than potassium. Therefore, to invade such environments, while maintaining excess of potassium over sodium in the cytoplasm, primordial cells needed means to extrude sodium ions. The foray into new, sodium-rich habitats was the likely driving force behind the evolution of diverse redox-, light-, chemically-, or osmotically-dependent sodium export pumps and the increase of membrane tightness. Here we present a scenario that details how the interplay between several, initially independent sodium pumps might have triggered the evolution of sodium-dependent membrane bioenergetics, followed by the separate emergence of the proton-dependent bioenergetics in archaea and bacteria. We also discuss the development of systems that utilize the sodium/potassium gradient across the cell membranes.

Active Sites of Spinoxin, a Potassium Channel Scorpion Toxin, Elucidated by Systematic Alanine Scanning.

Science.gov (United States)

Peigneur, Steve; Yamaguchi, Yoko; Kawano, Chihiro; Nose, Takeru; Nirthanan, Selvanayagam; Gopalakrishnakone, Ponnampalam; Tytgat, Jan; Sato, Kazuki

2016-05-31

Peptide toxins from scorpion venoms constitute the largest group of toxins that target the voltage-gated potassium channel (Kv). Spinoxin (SPX) isolated from the venom of scorpion Heterometrus spinifer is a 34-residue peptide neurotoxin cross-linked by four disulfide bridges. SPX is a potent inhibitor of Kv1.3 potassium channels (IC50 = 63 nM), which are considered to be valid molecular targets in the diagnostics and therapy of various autoimmune disorders and cancers. Here we synthesized 25 analogues of SPX and analyzed the role of each amino acid in SPX using alanine scanning to study its structure-function relationships. All synthetic analogues showed similar disulfide bond pairings and secondary structures as native SPX. Alanine replacements at Lys(23), Asn(26), and Lys(30) resulted in loss of activity against Kv1.3 potassium channels, whereas replacements at Arg(7), Met(14), Lys(27), and Tyr(32) also largely reduced inhibitory activity. These results suggest that the side chains of these amino acids in SPX play an important role in its interaction with Kv1.3 channels. In particular, Lys(23) appears to be a key residue that underpins Kv1.3 channel inhibition. Of these seven amino acid residues, four are basic amino acids, suggesting that the positive electrostatic potential on the surface of SPX is likely required for high affinity interaction with Kv1.3 channels. This study provides insight into the structure-function relationships of SPX with implications for the rational design of new lead compounds targeting potassium channels with high potency.

Effects of Near-Infrared Laser on Neural Cell Activity

International Nuclear Information System (INIS)

Mochizuki-Oda, Noriko; Kataoka, Yosky; Yamada, Hisao; Awazu, Kunio

2004-01-01

Near-infrared laser has been used to relieve patients from various kinds of pain caused by postherpetic neuralgesia, myofascial dysfunction, surgical and traumatic wound, cancer, and rheumatoid arthritis. Clinically, He-Ne (λ=632.8 nm, 780 nm) and Ga-Al-As (805 ± 25 nm) lasers are used to irradiate trigger points or nerve ganglion. However the precise mechanisms of such biological actions of the laser have not yet been resolved. Since laser therapy is often effective to suppress the pain caused by hyperactive excitation of sensory neurons, interactions with laser light and neural cells are suggested. As neural excitation requires large amount of energy liberated from adenosine triphosphate (ATP), we examined the effect of 830-nm laser irradiation on the energy metabolism of the rat central nervous system and isolated mitochondria from brain. The diode laser was applied for 15 min with irradiance of 4.8 W/cm2 on a 2 mm-diameter spot at the brain surface. Tissue ATP content of the irradiated area in the cerebral cortex was 19% higher than that of the non-treated area (opposite side of the cortex), whereas the ADP content showed no significant difference. Irradiation at another wavelength (652 nm) had no effect on either ATP or ADP contents. The temperature of the brain tissue was increased 4.5-5.0 deg. C during the irradiation of both 830-nm and 652-nm laser light. Direct irradiation of the mitochondrial suspension did not show any wavelength-dependent acceleration of respiration rate nor ATP synthesis. These results suggest that the increase in tissue ATP content did not result from the thermal effect, but from specific effect of the laser operated at 830 nm. Electrophysiological studies showed the hyperpolarization of membrane potential of isolated neurons and decrease in membrane resistance with irradiation of the laser, suggesting an activation of potassium channels. Intracellular ATP is reported to regulate some kinds of potassium channels. Possible mechanisms

Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting.

Science.gov (United States)

Morozova, Ekaterina O; Myroshnychenko, Maxym; Zakharov, Denis; di Volo, Matteo; Gutkin, Boris; Lapish, Christopher C; Kuznetsov, Alexey

2016-10-01

In the ventral tegmental area (VTA), interactions between dopamine (DA) and γ-aminobutyric acid (GABA) neurons are critical for regulating DA neuron activity and thus DA efflux. To provide a mechanistic explanation of how GABA neurons influence DA neuron firing, we developed a circuit model of the VTA. The model is based on feed-forward inhibition and recreates canonical features of the VTA neurons. Simulations revealed that γ-aminobutyric acid (GABA) receptor (GABAR) stimulation can differentially influence the firing pattern of the DA neuron, depending on the level of synchronization among GABA neurons. Asynchronous activity of GABA neurons provides a constant level of inhibition to the DA neuron and, when removed, produces a classical disinhibition burst. In contrast, when GABA neurons are synchronized by common synaptic input, their influence evokes additional spikes in the DA neuron, resulting in increased measures of firing and bursting. Distinct from previous mechanisms, the increases were not based on lowered firing rate of the GABA neurons or weaker hyperpolarization by the GABAR synaptic current. This phenomenon was induced by GABA-mediated hyperpolarization of the DA neuron that leads to decreases in intracellular calcium (Ca 2+ ) concentration, thus reducing the Ca 2+ -dependent potassium (K + ) current. In this way, the GABA-mediated hyperpolarization replaces Ca 2+ -dependent K + current; however, this inhibition is pulsatile, which allows the DA neuron to fire during the rhythmic pauses in inhibition. Our results emphasize the importance of inhibition in the VTA, which has been discussed in many studies, and suggest a novel mechanism whereby computations can occur locally. Copyright © 2016 the American Physiological Society.

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

Membrane Currents in Airway Smooth Muscle: Mechanisms and Therapeutic Implications

Directory of Open Access Journals (Sweden)

Luke J Janssen

1997-01-01

Full Text Available Electrophysiological and pharmacological techniques were used to characterize the membrane conductance changes underlying spasmogen-evoked depolarization in airway smooth muscle (ASM. Changes included a transient activation of chloride ion channels and prolonged suppression of potassium ion channels; both changes are triggered by release of internally sequestered calcium ion and in turn cause opening of voltage-dependent calcium channels. The resultant influx of calcium ions contributes to contraction as well as to refilling of the internal calcium ion pool. Bronchodilators, on the other hand, act in part through activation of potassium channels, with consequent closure of calcium channels. The tools used to study ion channels in ASM are described, and the investigations of the roles of ion channels in ASM physiology (autacoid-evoked depolarization and hyperpolarization and pathophysiology (airway hyperresponsiveness are summarized. Finally, how the relationship between ion channels and ASM function/dysfunction may relate to the treatment of asthma and related breathing disorders is discussed.

Lunar atmosphere. How surface composition and meteoroid impacts mediate sodium and potassium in the lunar exosphere.

Science.gov (United States)

Colaprete, A; Sarantos, M; Wooden, D H; Stubbs, T J; Cook, A M; Shirley, M

2016-01-15

Despite being trace constituents of the lunar exosphere, sodium and potassium are the most readily observed species due to their bright line emission. Measurements of these species by the Ultraviolet and Visible Spectrometer (UVS) on the Lunar Atmosphere and Dust Environment Explorer (LADEE) have revealed unambiguous temporal and spatial variations indicative of a strong role for meteoroid bombardment and surface composition in determining the composition and local time dependence of the Moon's exosphere. Observations show distinct lunar day (monthly) cycles for both species as well as an annual cycle for sodium. The first continuous measurements for potassium show a more repeatable variation across lunations and an enhancement over KREEP (Potassium Rare Earth Elements and Phosphorus) surface regions, revealing a strong dependence on surface composition. Copyright © 2016, American Association for the Advancement of Science.

Accumulation of slowly activating delayed rectifier potassium current (IKs) in canine ventricular myocytes

DEFF Research Database (Denmark)

Stengl, Milan; Volders, Paul G A; Thomsen, Morten Bækgaard

2003-01-01

In guinea-pig ventricular myocytes, in which the deactivation of slowly activating delayed rectifier potassium current (IKs) is slow, IKs can be increased by rapid pacing as a result of incomplete deactivation and subsequent current accumulation. Whether accumulation of IKs occurs in dogs, in which...

Isoflurane depolarizes bronchopulmonary C neurons by inhibiting transient A-type and delayed rectifier potassium channels.

Science.gov (United States)

Zhang, Zhenxiong; Zhuang, Jianguo; Zhang, Cancan; Xu, Fadi

2013-04-01

Inhalation of isoflurane (ISO), a widely used volatile anesthetic, can produce clinical tachypnea. In dogs, this response is reportedly mediated by bronchopulmonary C-fibers (PCFs), but the relevant mechanisms remain unclear. Activation of transient A-type potassium current (IA) channels and delayed rectifier potassium current (IK) channels hyperpolarizes neurons, and inhibition of both channels by ISO increases neural firing. Due to the presence of these channels in the cell bodies of rat PCFs, we determined whether ISO could stimulate PCFs to produce tachypnea in anesthetized rats, and, if so, whether this response resulted from ISO-induced depolarization of the pulmonary C neurons via the inhibition of IA and IK. We recorded ventilatory responses to 5% ISO exposure in anesthetized rats before and after blocking PCF conduction and the responses of pulmonary C neurons (extracellularly recorded) to ISO exposure. ISO-induced (1mM) changes in pulmonary C neuron membrane potential and IA/IK were tested using the perforated patch clamp technique. We found that: (1) ISO inhalation evoked a brief tachypnea (∼7s) and that this response disappeared after blocking PCF conduction; (2) the ISO significantly elevated (by 138%) the firing rate of most pulmonary C neurons (17 out of 21) in the nodose ganglion; and (3) ISO perfusion depolarized the pulmonary C neurons in the vitro and inhibited both IA and IK, and this evoked-depolarization was largely diminished after blocking both IA and IK. Our results suggest that ISO is able to stimulate PCFs to elicit tachypnea in rats, at least partly, via inhibiting IA and IK, thereby depolarizing the pulmonary C neurons. Copyright © 2013. Published by Elsevier B.V.

Potassium distribution in sugar cane

International Nuclear Information System (INIS)

Medina, N.H.

2014-01-01

In this work the distribution of potassium in sugarcane has been studied during its growth in two different conditions. In the first one the sugarcane soil was prepared with natural fertilizers, using sugarcane bagasse and, in another plantation the soil was prepared with commercial fertilizer NPK with a proportion of 10-10-10. For the measurement of potassium concentration in each part of the plant, gamma ray spectrometry techniques have been used to measure gamma-rays emitted from the radioisotope 40 K present in the sugarcane samples. The concentration of potassium in roots, stems and leaves were measured periodically. The results for sugarcane cultivated in soil with natural fertilizer show a higher concentration of potassium at the beginning of plant development and over time there is an oscillatory behavior in this concentration in each part of the plant, reaching a lower concentration in the adult plant. The results for the plant grown in soil with NPK fertilizer, indicate that the potassium concentration is higher in the stem at the beginning of cultivation and remained practically constant over time in various parts of the plant, with higher values in the leaves and stem than at the root. On the other hand, the results obtained using fertilizer NPK shows a lower potassium concentration, since the fertilizer provoked a much higher growth rate. (author)

Terbinafine is a novel and selective activator of the two-pore domain potassium channel TASK3.

Science.gov (United States)

Wright, Paul D; Veale, Emma L; McCoull, David; Tickle, David C; Large, Jonathan M; Ococks, Emma; Gothard, Gemma; Kettleborough, Catherine; Mathie, Alistair; Jerman, Jeffrey

2017-11-04

Two-pore domain potassium channels (K2Ps) are characterized by their four transmembrane domain and two-pore topology. They carry background (or leak) potassium current in a variety of cell types. Despite a number of important roles there is currently a lack of pharmacological tools with which to further probe K2P function. We have developed a cell-based thallium flux assay, using baculovirus delivered TASK3 (TWIK-related acid-sensitive K + channel 3, KCNK9, K2P9.1) with the aim of identifying novel, selective TASK3 activators. After screening a library of 1000 compounds, including drug-like and FDA approved molecules, we identified Terbinafine as an activator of TASK3. In a thallium flux assay a pEC50 of 6.2 ( ±0.12) was observed. When Terbinafine was screened against TASK2, TREK2, THIK1, TWIK1 and TRESK no activation was observed in thallium flux assays. Several analogues of Terbinafine were also purchased and structure activity relationships examined. To confirm Terbinafine's activation of TASK3 whole cell patch clamp electrophysiology was carried out and clear potentiation observed in both the wild type channel and the pathophysiological, Birk-Barel syndrome associated, G236R TASK3 mutant. No activity at TASK1 was observed in electrophysiology studies. In conclusion, we have identified the first selective activator of the two-pore domain potassium channel TASK3. Copyright © 2017 Elsevier Inc. All rights reserved.

Docetaxel modulates the delayed rectifier potassium current (IK) and ATP-sensitive potassium current (IKATP) in human breast cancer cells.

Science.gov (United States)

Sun, Tao; Song, Zhi-Guo; Jiang, Da-Qing; Nie, Hong-Guang; Han, Dong-Yun

2015-04-01

Ion channel expression and activity may be affected during tumor development and cancer growth. Activation of potassium (K(+)) channels in human breast cancer cells is reported to be involved in cell cycle progression. In this study, we investigated the effects of docetaxel on the delayed rectifier potassium current (I K) and the ATP-sensitive potassium current (I KATP) in two human breast cancer cell lines, MCF-7 and MDA-MB-435S, using the whole-cell patch-clamp technique. Our results show that docetaxel inhibited the I K and I KATP in both cell lines in a dose-dependent manner. Compared with the control at a potential of +60 mV, treatment with docetaxel at doses of 0.1, 1, 5, and 10 µM significantly decreased the I K in MCF-7 cells by 16.1 ± 3.5, 30.2 ± 5.2, 42.5 ± 4.3, and 46.4 ± 9% (n = 5, P < 0.05), respectively and also decreased the I KATP at +50 mV. Similar results were observed in MDA-MB-435S cells. The G-V curves showed no significant changes after treatment of either MCF-7 or MDA-MB-435S cells with 10 μM docetaxel. The datas indicate that the possible mechanisms of I K and I KATP inhibition by docetaxel may be responsible for its effect on the proliferation of human breast cancer cells.

Data on electrical properties of nickel modified potassium polytitanates compacted powders.

Science.gov (United States)

Goffman, V G; Gorokhovsky, A V; Gorshkov, N V; Fedorov, F S; Tretychenko, E V; Sevrugin, A V

2015-09-01

Potassium polytitanates are new promising type of ferroelectric ceramic materials with high ionic conductivity, highly polarizable structure and extremely high permittivity. Its structure is formed by [TiO6] octahedral units to layers with mobile potassium and hydroxonium ions in-between. The treatment in solutions containing nickel ions allows forming heterostructured materials which consist of potassium polytitanate particles intercalated by Ni(2+) ions and/or decorated by nickel oxides NiO x . This modification route is fully dependant on solution pH, i.e. in acidic solutions the intercalation process prevails, in alkaline solutions potassium polytitanate is mostly decorated by the oxides. Therefore, electronic structure and electrical properties can be regulated depending on modification conditions, pH and ions concentration. Here we report the data on electric properties of potassium titanate modified in nickel sulfate solutions at different pH.

Data on electrical properties of nickel modified potassium polytitanates compacted powders

Directory of Open Access Journals (Sweden)

V.G. Goffman

2015-09-01

Full Text Available Potassium polytitanates are new promising type of ferroelectric ceramic materials with high ionic conductivity, highly polarizable structure and extremely high permittivity. Its structure is formed by [TiO6] octahedral units to layers with mobile potassium and hydroxonium ions in-between. The treatment in solutions containing nickel ions allows forming heterostructured materials which consist of potassium polytitanate particles intercalated by Ni2+ ions and/or decorated by nickel oxides NiOx. This modification route is fully dependant on solution pH, i.e. in acidic solutions the intercalation process prevails, in alkaline solutions potassium polytitanate is mostly decorated by the oxides. Therefore, electronic structure and electrical properties can be regulated depending on modification conditions, pH and ions concentration. Here we report the data on electric properties of potassium titanate modified in nickel sulfate solutions at different pH.

Single-Shot-RARE for rapid 3D hyperpolarized metabolic ex vivo tissue imaging: RF-pulse design for semi-dense spectra

DEFF Research Database (Denmark)

Magnusson, P.O.; Jensen, Pernille Rose; Dyrby, Tim Bjørn

MRS of hyperpolarized (HP) 13C-enriched compounds is a promising method for in vivo cancer diagnosis . Sentinel lymph node ex vivo tissue sample histology used in clinical routine for breast cancer metastasis diagnosis requires time consuming sample analysis. 3D-HP-MRSI can potentially speed up...

Direct hyperpolarization of micro- and nanodiamonds for bioimaging applications - Considerations on particle size, functionalization and polarization loss

Science.gov (United States)

Kwiatkowski, Grzegorz; Jähnig, Fabian; Steinhauser, Jonas; Wespi, Patrick; Ernst, Matthias; Kozerke, Sebastian

2018-01-01

Due to the inherently long relaxation time of 13C spins in diamond, the nuclear polarization enhancement obtained with dynamic nuclear polarization can be preserved for a time on the order of about one hour, opening up an opportunity to use diamonds as a new class of long-lived contrast agents. The present communication explores the feasibility of using 13C spins in directly hyperpolarized diamonds for MR imaging including considerations for potential in vivo applications.

Hyperpolarized 129Xe MRI: A viable functional lung imaging modality?

International Nuclear Information System (INIS)

Patz, Samuel; Hersman, F. William; Muradian, Iga; Hrovat, Mirko I.; Ruset, Iulian C.; Ketel, Stephen; Jacobson, Francine; Topulos, George P.; Hatabu, Hiroto; Butler, James P.

2007-01-01

The majority of researchers investigating hyperpolarized gas MRI as a candidate functional lung imaging modality have used 3 He as their imaging agent of choice rather than 129 Xe. This preference has been predominantly due to, 3 He providing stronger signals due to higher levels of polarization and higher gyromagnetic ratio, as well as its being easily available to more researchers due to availability of polarizers (USA) or ease of gas transport (Europe). Most researchers agree, however, that hyperpolarized 129 Xe will ultimately emerge as the imaging agent of choice due to its unlimited supply in nature and its falling cost. Our recent polarizer technology delivers vast improvements in hyperpolarized 129 Xe output. Using this polarizer, we have demonstrated the unique property of xenon to measure alveolar surface area noninvasively. In this article, we describe our human protocols and their safety, and our results for the measurement of the partial pressure of pulmonary oxygen (pO 2 ) by observation of 129 Xe signal decay. We note that the measurement of pO 2 by observation of 129 Xe signal decay is more complex than that for 3 He because of an additional signal loss mechanism due to interphase diffusion of 129 Xe from alveolar gas spaces to septal tissue. This results in measurements of an equivalent pO 2 that accounts for both traditional T 1 decay from pO 2 and that from interphase diffusion. We also provide an update on new technological advancements that form the foundation for an improved compact design polarizer as well as improvements that provide another order-of-magnitude scale-up in xenon polarizer output

Astrocytic mitochondrial membrane hyperpolarization following extended oxygen and glucose deprivation.

Directory of Open Access Journals (Sweden)

Andrej Korenić

Full Text Available Astrocytes can tolerate longer periods of oxygen and glucose deprivation (OGD as compared to neurons. The reasons for this reduced vulnerability are not well understood. Particularly, changes in mitochondrial membrane potential (Δψ(m in astrocytes, an indicator of the cellular redox state, have not been investigated during reperfusion after extended OGD exposure. Here, we subjected primary mouse astrocytes to glucose deprivation (GD, OGD and combinations of both conditions varying in duration and sequence. Changes in Δψ(m, visualized by change in the fluorescence of JC-1, were investigated within one hour after reconstitution of oxygen and glucose supply, intended to model in vivo reperfusion. In all experiments, astrocytes showed resilience to extended periods of OGD, which had little effect on Δψ(m during reperfusion, whereas GD caused a robust Δψ(m negativation. In case no Δψ(m negativation was observed after OGD, subsequent chemical oxygen deprivation (OD induced by sodium azide caused depolarization, which, however, was significantly delayed as compared to normoxic group. When GD preceded OD for 12 h, Δψ(m hyperpolarization was induced by both GD and subsequent OD, but significant interaction between these conditions was not detected. However, when GD was extended to 48 h preceding OGD, hyperpolarization enhanced during reperfusion. This implicates synergistic effects of both conditions in that sequence. These findings provide novel information regarding the role of the two main substrates of electron transport chain (glucose and oxygen and their hyperpolarizing effect on Δψ(m during substrate deprivation, thus shedding new light on mechanisms of astrocyte resilience to prolonged ischemic injury.

Molecular interactions involved in proton-dependent gating in KcsA potassium channels

Science.gov (United States)

Posson, David J.; Thompson, Ameer N.; McCoy, Jason G.

2013-01-01

The bacterial potassium channel KcsA is gated open by the binding of protons to amino acids on the intracellular side of the channel. We have identified, via channel mutagenesis and x-ray crystallography, two pH-sensing amino acids and a set of nearby residues involved in molecular interactions that influence gating. We found that the minimal mutation of one histidine (H25) and one glutamate (E118) near the cytoplasmic gate completely abolished pH-dependent gating. Mutation of nearby residues either alone or in pairs altered the channel’s response to pH. In addition, mutations of certain pairs of residues dramatically increased the energy barriers between the closed and open states. We proposed a Monod–Wyman–Changeux model for proton binding and pH-dependent gating in KcsA, where H25 is a “strong” sensor displaying a large shift in pKa between closed and open states, and E118 is a “weak” pH sensor. Modifying model parameters that are involved in either the intrinsic gating equilibrium or the pKa values of the pH-sensing residues was sufficient to capture the effects of all mutations. PMID:24218397

The role of hyperpolarized 129xenon in MR imaging of pulmonary function

International Nuclear Information System (INIS)

Ebner, Lukas; Kammerman, Jeff; Driehuys, Bastiaan; Schiebler, Mark L.; Cadman, Robert V.; Fain, Sean B.

2017-01-01

Highlights: • Recent advances in hyperpolarized 129Xe MRI are reviewed. • Xenon MRI allows for functional imaging of ventilation, diffusion, and gas exchange. • Xenon’s unique gas exchange imaging capabilities are highlighted. • Applications to obstructive and restrictive lung diseases are presented. • These advances are ready for translation to clinical applications. - Abstract: In the last two decades, functional imaging of the lungs using hyperpolarized noble gases has entered the clinical stage. Both helium ( 3 He) and xenon ( 129 Xe) gas have been thoroughly investigated for their ability to assess both the global and regional patterns of lung ventilation. With advances in polarizer technology and the current transition towards the widely available 129 Xe gas, this method is ready for translation to the clinic. Currently, hyperpolarized (HP) noble gas lung MRI is limited to selected academic institutions; yet, the promising results from initial clinical trials have drawn the attention of the pulmonary medicine community. HP 129 Xe MRI provides not only 3-dimensional ventilation imaging, but also unique capabilities for probing regional lung physiology. In this review article, we aim to (1) provide a brief overview of current ventilation MR imaging techniques, (2) emphasize the role of HP 129 Xe MRI within the array of different imaging strategies, (3) discuss the unique imaging possibilities with HP 129 Xe MRI, and (4) propose clinical applications.

Multistability in a neuron model with extracellular potassium dynamics

Science.gov (United States)

Wu, Xing-Xing; Shuai, J. W.

2012-06-01

Experiments show a primary role of extracellular potassium concentrations in neuronal hyperexcitability and in the generation of epileptiform bursting and depolarization blocks without synaptic mechanisms. We adopt a physiologically relevant hippocampal CA1 neuron model in a zero-calcium condition to better understand the function of extracellular potassium in neuronal seizurelike activities. The model neuron is surrounded by interstitial space in which potassium ions are able to accumulate. Potassium currents, Na+-K+ pumps, glial buffering, and ion diffusion are regulatory mechanisms of extracellular potassium. We also consider a reduced model with a fixed potassium concentration. The bifurcation structure and spiking frequency of the two models are studied. We show that, besides hyperexcitability and bursting pattern modulation, the potassium dynamics can induce not only bistability but also tristability of different firing patterns. Our results reveal the emergence of the complex behavior of multistability due to the dynamical [K+]o modulation on neuronal activities.

Intracellular mediators of potassium-induced aldosterone secretion

International Nuclear Information System (INIS)

Ganguly, A.; Chiou, S.; Davis, J.S.

1990-01-01

We have investigated the intracellular messengers of potassium in eliciting aldosterone secretion in calf adrenal glomerulosa cells since there were unresolved issues relating to the role of phosphoinositides, cAMP and protein kinases. We observed no evidence of hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) in 3 H-inositol labeled alf adrenal cells or increase of cAMP in response to potassium. Addition of calcium channel blocker, nitrendipine after stimulating adrenal glomerulosa cells with potassium, markedly inhibited aldosterone secretion. A calmodulin inhibitor (W-7) produced greater reduction of aldosterone secretion than an inhibitor of protein kinase C (H-7). These results suggest that a rise in cytosolic free calcium concentration through voltage-dependent calcium channel and calmodulin are the critical determinants of aldosterone secretion stimulated by potassium

Evaluation of hyperpolarized [1-¹³C]-pyruvate by magnetic resonance to detect ionizing radiation effects in real time.

Science.gov (United States)

Sandulache, Vlad C; Chen, Yunyun; Lee, Jaehyuk; Rubinstein, Ashley; Ramirez, Marc S; Skinner, Heath D; Walker, Christopher M; Williams, Michelle D; Tailor, Ramesh; Court, Laurence E; Bankson, James A; Lai, Stephen Y

2014-01-01

Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS). Since tumor cells neutralize ROS by utilizing reducing equivalents, we hypothesized that measurements of reducing potential using real-time hyperpolarized (HP) magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) can serve as a surrogate marker of IR induced ROS. This hypothesis was tested in a pre-clinical model of anaplastic thyroid carcinoma (ATC), an aggressive head and neck malignancy. Human ATC cell lines were utilized to test IR effects on ROS and reducing potential in vitro and [1-¹³C] pyruvate HP-MRS/MRSI imaging of ATC orthotopic xenografts was used to study in vivo effects of IR. IR increased ATC intra-cellular ROS levels resulting in a corresponding decrease in reducing equivalent levels. Exogenous manipulation of cellular ROS and reducing equivalent levels altered ATC radiosensitivity in a predictable manner. Irradiation of ATC xenografts resulted in an acute drop in reducing potential measured using HP-MRS, reflecting the shunting of reducing equivalents towards ROS neutralization. Residual tumor tissue post irradiation demonstrated heterogeneous viability. We have adapted HP-MRS/MRSI to non-invasively measure IR mediated changes in tumor reducing potential in real time. Continued development of this technology could facilitate the development of an adaptive clinical algorithm based on real-time adjustments in IR dose and dose mapping.

Evaluation of hyperpolarized [1-¹³C]-pyruvate by magnetic resonance to detect ionizing radiation effects in real time.

Directory of Open Access Journals (Sweden)

Vlad C Sandulache

Full Text Available Ionizing radiation (IR cytotoxicity is primarily mediated through reactive oxygen species (ROS. Since tumor cells neutralize ROS by utilizing reducing equivalents, we hypothesized that measurements of reducing potential using real-time hyperpolarized (HP magnetic resonance spectroscopy (MRS and spectroscopic imaging (MRSI can serve as a surrogate marker of IR induced ROS. This hypothesis was tested in a pre-clinical model of anaplastic thyroid carcinoma (ATC, an aggressive head and neck malignancy. Human ATC cell lines were utilized to test IR effects on ROS and reducing potential in vitro and [1-¹³C] pyruvate HP-MRS/MRSI imaging of ATC orthotopic xenografts was used to study in vivo effects of IR. IR increased ATC intra-cellular ROS levels resulting in a corresponding decrease in reducing equivalent levels. Exogenous manipulation of cellular ROS and reducing equivalent levels altered ATC radiosensitivity in a predictable manner. Irradiation of ATC xenografts resulted in an acute drop in reducing potential measured using HP-MRS, reflecting the shunting of reducing equivalents towards ROS neutralization. Residual tumor tissue post irradiation demonstrated heterogeneous viability. We have adapted HP-MRS/MRSI to non-invasively measure IR mediated changes in tumor reducing potential in real time. Continued development of this technology could facilitate the development of an adaptive clinical algorithm based on real-time adjustments in IR dose and dose mapping.

ACh-evoked membrane hyperpolarization in smooth muscle cells of rat vas deferens in vitro: Involvement of K+ channels and NO%一氧化氮和K+通道参与乙酰胆碱引起的大鼠离体输精管平滑肌细胞超极化

Institute of Scientific and Technical Information of China (English)

范平; 李丽; 刘政江; 司军强; 张志琴; 赵磊; 马克涛

2007-01-01

To explore the underlying mechanism of acetylcholine (Ach)-evoked membrane hyperpolarizing response in isolated rat vas deferens smooth muscle cells (SMCs), intracellular microelectrode recording technique and intracellular microelectrophoresis fluorescent staining technique were used to study Ach-evoked membrane hyperpolarizing response in SMCs freshly isolated from Wistar rat vas deferens. By using microelectrodes containing fluorescent dye 0.1% propidium iodide (PI), 37 and 17 cells were identified as SMCs in outer longitudinal and inner circular muscular layers, respectively. The resting membrane potentials of SMCs were (–53.56±3.88) mV and (–51.62±4.27) mV, respectively. The membrane input resistances were (2 245.60±372.50) MΩ and (2 101.50±513.50) MΩ , respectively. Ach evoked membrane hyperpolarizing response in a concentration-dependent manner with an of 36 μmol/L. This action of Ach was abolished by both a non-sepcific muscarinic (M) receptor antagonist atropine (1 μmol/L) and a selective M 3 receptor antagonist diphenylacetoxy-N-methylpiperidine-methiodide (DAMP, 100 nmol/L). Ach-evoked membrane hyperpolarization was also abolished by a nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 300 μmol/L) and suppressed by an ATP-sensitive potassium (K ATP ) channel blocker glipizide (5 μmol/L) and an inward rectifier potassium (K ir ) channel inhibitor bariumion (50 μmol/L). A combination of glipizide and bariumion abolished Ach-evoked membrane hyperpolarizing response. The results suggest that Ach-evoked membrane hyperpolarization in rat vas deferens SMCs is mediated by M 3 receptor followed with activation of K ATP channels, K ir channels, and NO release.%本文旨在探讨大鼠新鲜离体输精管平滑肌细胞中乙酰胆碱(acetylcholine,Ach)引起超极化反应的机制,采用细胞内微电极记录技术和细胞内荧光标记技术研究Ach对大鼠输精管不同走行方向平滑肌细�

The Hyperpolarization-Activated Current Determines Synaptic Excitability, Calcium Activity and Specific Viability of Substantia Nigra Dopaminergic Neurons

Directory of Open Access Journals (Sweden)

Carmen Carbone

2017-06-01

Full Text Available Differential vulnerability between Substantia Nigra pars compacta (SNpc and Ventral Tegmental Area (VTA dopaminergic (DAergic neurons is a hallmark of Parkinson’s disease (PD. Understanding the molecular bases of this key histopathological aspect would foster the development of much-needed disease-modifying therapies. Non-heterogeneous DAergic degeneration is present in both toxin-based and genetic animal models, suggesting that cellular specificity, rather than causing factors, constitutes the background for differential vulnerability. In this regard, we previously demonstrated that MPP+, a neurotoxin able to cause selective nigrostriatal degeneration in animal rodents and primates, inhibits the Hyperpolarization-activated current (Ih in SNpc DAergic neurons and that pharmacological Ih antagonism causes potentiation of evoked Excitatory post-synaptic potentials (EPSPs. Of note, the magnitude of such potentiation is greater in the SNpc subfield, consistent with higher Ih density. In the present work, we show that Ih block-induced synaptic potentiation leads to the amplification of somatic calcium responses (SCRs in vitro. This effect is specific for the SNpc subfield and largely mediated by L-Type calcium channels, as indicated by sensitivity to the CaV 1 blocker isradipine. Furthermore, Ih is downregulated by low intracellular ATP and determines the efficacy of GABAergic inhibition in SNpc DAergic neurons. Finally, we show that stereotaxic administration of Ih blockers causes SNpc-specific neurodegeneration and hemiparkinsonian motor phenotype in rats. During PD progression, Ih downregulation may result from mitochondrial dysfunction and, in concert with PD-related disinhibition of excitatory inputs, determine a SNpc-specific disease pathway.

Dependence of radiocaesium biological half-life in freshwater fish on water potassium concentration and temperature

International Nuclear Information System (INIS)

Carreiro, M.C.V.; Corisco, J.A.G.

1998-01-01

Short-term experiments (35-49 days) showed that the rate of cesium elimination from fish increases with increasing potassium concentration in water (the biological half-life decreases); this, however, is only true of the potassium concentration range of 0.35 to 3.5 ppm, whereas higher potassium concentrations do not seem to affect the elimination rate. Decrease in water temperature within the 20 degC to 5 degC range slows down the cesium elimination process. (P.A.)

Real-time two-dimensional imaging of potassium ion distribution using an ion semiconductor sensor with charged coupled device technology.

Science.gov (United States)

Hattori, Toshiaki; Masaki, Yoshitomo; Atsumi, Kazuya; Kato, Ryo; Sawada, Kazuaki

2010-01-01

Two-dimensional real-time observation of potassium ion distributions was achieved using an ion imaging device based on charge-coupled device (CCD) and metal-oxide semiconductor technologies, and an ion selective membrane. The CCD potassium ion image sensor was equipped with an array of 32 × 32 pixels (1024 pixels). It could record five frames per second with an area of 4.16 × 4.16 mm(2). Potassium ion images were produced instantly. The leaching of potassium ion from a 3.3 M KCl Ag/AgCl reference electrode was dynamically monitored in aqueous solution. The potassium ion selective membrane on the semiconductor consisted of plasticized poly(vinyl chloride) (PVC) with bis(benzo-15-crown-5). The addition of a polyhedral oligomeric silsesquioxane to the plasticized PVC membrane greatly improved adhesion of the membrane onto Si(3)N(4) of the semiconductor surface, and the potential response was stabilized. The potential response was linear from 10(-2) to 10(-5) M logarithmic concentration of potassium ion. The selectivity coefficients were K(K(+),Li(+))(pot) = 10(-2.85), K(K(+),Na(+))(pot) = 10(-2.30), K(K(+),Rb(+))(pot) =10(-1.16), and K(K(+),Cs(+))(pot) = 10(-2.05).

The Trk Potassium Transporter Is Required for RsmB-Mediated Activation of Virulence in the Phytopathogen Pectobacterium wasabiae.

Science.gov (United States)

Valente, Rita S; Xavier, Karina B

2016-01-15

Pectobacterium wasabiae (previously known as Erwinia carotovora) is an important plant pathogen that regulates the production of plant cell wall-degrading enzymes through an N-acyl homoserine lactone-based quorum sensing system and through the GacS/GacA two-component system (also known as ExpS/ExpA). At high cell density, activation of GacS/GacA induces the expression of RsmB, a noncoding RNA that is essential for the activation of virulence in this bacterium. A genetic screen to identify regulators of RsmB revealed that mutants defective in components of a putative Trk potassium transporter (trkH and trkA) had decreased rsmB expression. Further analysis of these mutants showed that changes in potassium concentration influenced rsmB expression and consequent tissue damage in potato tubers and that this regulation required an intact Trk system. Regulation of rsmB expression by potassium via the Trk system occurred even in the absence of the GacS/GacA system, demonstrating that these systems act independently and are both required for full activation of RsmB and for the downstream induction of virulence in potato infection assays. Overall, our results identified potassium as an essential environmental factor regulating the Rsm system, and the consequent induction of virulence, in the plant pathogen P. wasabiae. Crop losses from bacterial diseases caused by pectolytic bacteria are a major problem in agriculture. By studying the regulatory pathways involved in controlling the expression of plant cell wall-degrading enzymes in Pectobacterium wasabiae, we showed that the Trk potassium transport system plays an important role in the regulation of these pathways. The data presented further identify potassium as an important environmental factor in the regulation of virulence in this plant pathogen. We showed that a reduction in virulence can be achieved by increasing the extracellular concentration of potassium. Therefore, this work highlights how elucidation of the

Effects of extracellular potassium diffusion on electrically coupled neuron networks

Science.gov (United States)

Wu, Xing-Xing; Shuai, Jianwei

2015-02-01

Potassium accumulation and diffusion during neuronal epileptiform activity have been observed experimentally, and potassium lateral diffusion has been suggested to play an important role in nonsynaptic neuron networks. We adopt a hippocampal CA1 pyramidal neuron network in a zero-calcium condition to better understand the influence of extracellular potassium dynamics on the stimulus-induced activity. The potassium concentration in the interstitial space for each neuron is regulated by potassium currents, Na+-K+ pumps, glial buffering, and ion diffusion. In addition to potassium diffusion, nearby neurons are also coupled through gap junctions. Our results reveal that the latency of the first spike responding to stimulus monotonically decreases with increasing gap-junction conductance but is insensitive to potassium diffusive coupling. The duration of network oscillations shows a bell-like shape with increasing potassium diffusive coupling at weak gap-junction coupling. For modest electrical coupling, there is an optimal K+ diffusion strength, at which the flow of potassium ions among the network neurons appropriately modulates interstitial potassium concentrations in a degree that provides the most favorable environment for the generation and continuance of the action potential waves in the network.

Kinetic studies of potassium permanganate adsorption by activated carbon and its ability as ethylene oxidation material

Science.gov (United States)

Aprilliani, F.; Warsiki, E.; Iskandar, A.

2018-03-01

Generally, ethylene production in many horticultural products has been seen to be detrimental to the quality during storage and distribution process. For this reason, removing ethylene from storage or distribution atmosphere is needed to maintain the quality. One of the technologies that can be applied is the use of potassium permanganate (KMnO4). KMnO4 is an active compound that can be used as an oxidizing agent on ethylene removal process. KMnO4 is not recommended for direct used application. As the result, additional material is required to impregnate the potassium permanganate. The inert materials used are commercial activated carbon. Activated carbon is chosen because it has high surface area. The purpose of this research is to determine kinetics adsorption and oxidation model of ethylene removal material. The kinetics adsorption was determined using the pseudo-first and second-order kinetic models. The data on adsorption process show that the second-order equation is more suitable to express the adsorption process on this research. The analyzing of the ethylene oxidation capacity increased with time until it reaches an optimal value. The ethylene oxidation rate is able to be estimated by the formula r = 0.1967 [C2H4]0.99 [KMnO4]0.01; MSE = 0.44 %. The actual and estimation data of ethylene oxidation show that the model is fitted to describe the actual ethylene oxidation under same experimental conditions.

Potassium incorporation in fruits of South American tropical species

International Nuclear Information System (INIS)

Cid, Alberto S.; Anjos, Roberto M.; Macario, Kita D.; Veiga, Rodrigo; Lacerda, Thiago; Velasco, Hugo; Rizzoto, Marcos; Valladares, Daniel; Zamboni, Cibelle B.; Medeiros, Ilca M.A.

2010-01-01

Full text: This work proposes the use of a new mathematical model liable for describing the temporal evolution of potassium concentration in fruits of tropical species. Studies of the potassium incorporation are important for two main reasons: a) from the physiological point of view, this flux characterizes the dynamics of the demand of this essential macro nutrient during the gestation period of the fruit; and b) from a radioecological perspective, potassium is a chemical analogue of cesium, particularly of 137 Cs, one of the most important contaminant deposited after accidental releases of radionuclides into the environment. Therefore, describing the potassium incorporation, we can obtain crucial information on how this radionuclide can enter to the human food chain trough fruits. Nutrients accumulation by fruits has been extensively studied for different trees. These investigations have been addressed to evaluate the nutritional status at different stages of the fruit development, estimating the amount of the soil nutrient removal and then to know the better time to program the control and supply of fertilizers. The fruit quality and its aptitude to the conservation are closely related with de nutrient content and the equilibrium between them. The rate of the weight increment in fruit is not uniform. The dry mass accumulation is small in the initial period, later a more expressive increment is observed and, finally during the maturation period, a lower dry mass accumulation was observed. The lengths in days of each one of these grown phases depend of the fruit type. A sigmoid grown model appears to be a very good approximation. The nutrient accumulations follow characteristics patterns along these fruit grown phases. When food-chain model are used to describe the radionuclide key transfer processes for dose assessment, the steady state radionuclide concentration is assumed in each compartment. In many cases that could be a strict simplification of the reality

Potassium incorporation in fruits of South American tropical species

Energy Technology Data Exchange (ETDEWEB)

Cid, Alberto S.; Anjos, Roberto M.; Macario, Kita D.; Veiga, Rodrigo; Lacerda, Thiago [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil); Velasco, Hugo; Rizzoto, Marcos; Valladares, Daniel [Univesidad Nacional de San Luis (Argentina); Zamboni, Cibelle B.; Medeiros, Ilca M.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2010-07-01

Full text: This work proposes the use of a new mathematical model liable for describing the temporal evolution of potassium concentration in fruits of tropical species. Studies of the potassium incorporation are important for two main reasons: a) from the physiological point of view, this flux characterizes the dynamics of the demand of this essential macro nutrient during the gestation period of the fruit; and b) from a radioecological perspective, potassium is a chemical analogue of cesium, particularly of {sup 137}Cs, one of the most important contaminant deposited after accidental releases of radionuclides into the environment. Therefore, describing the potassium incorporation, we can obtain crucial information on how this radionuclide can enter to the human food chain trough fruits. Nutrients accumulation by fruits has been extensively studied for different trees. These investigations have been addressed to evaluate the nutritional status at different stages of the fruit development, estimating the amount of the soil nutrient removal and then to know the better time to program the control and supply of fertilizers. The fruit quality and its aptitude to the conservation are closely related with de nutrient content and the equilibrium between them. The rate of the weight increment in fruit is not uniform. The dry mass accumulation is small in the initial period, later a more expressive increment is observed and, finally during the maturation period, a lower dry mass accumulation was observed. The lengths in days of each one of these grown phases depend of the fruit type. A sigmoid grown model appears to be a very good approximation. The nutrient accumulations follow characteristics patterns along these fruit grown phases. When food-chain model are used to describe the radionuclide key transfer processes for dose assessment, the steady state radionuclide concentration is assumed in each compartment. In many cases that could be a strict simplification of the

Development of a hyperpolarized 129Xe system on 3T for the rat lungs

International Nuclear Information System (INIS)

Sato, Hiroshi; Enmi, Jun-ichiro; Hayashi, Takuya

2004-01-01

MRI (magnetic resonance imaging) with 129 Xe has gained much attention as a diagnostic methodology because of its affinity for lipids and possible polarization. The quantitative estimation of net detectability and stability of hyperpolarized 129 Xe in the dissolved phase in vivo is valuable to the development of clinical applications. The goal of this study was to develop a stable hyperpolarized 129 Xe experimental 3T system to statistically analyze the dissolved-phase 129 Xe signal in the rat lungs. The polarization of 129 Xe with buffer gases at the optical pumping cell was measured under adiabatic fast passage against the temperature of an oven and laser absorption at the cell. The gases were insuffiated into the lungs of Sprague-Dawley rats (n=15, 400-550 g) through an endotracheal tube under spontaneous respiration. Frequency-selective spectroscopy was performed for the gas phase and dissolved phase. We analyzed the 129 Xe signal in the dissolved phase to measure the chemical shift, T 2 * , delay and its ratio in a rat lungs on 3T. The polarizer was able to produce polarized gas (1.1±0.47%, 120 cm 3 ) hundreds of times with the laser absorption ratio (25%) kept constant at the cell. The optimal buffer gas ratio of 25-50% rendered the maximum signal in the dissolved phase. Two dominant peaks of 211.8±0.9 and 201.1±0.6 ppm were observed with a delay of 0.4±0.9 and 0.9±1.0 s from the gas phase spectra. The ratios of their average signal to that of the gas phase were 5.6±5.2% and 4.4±4.7%, respectively. The T 2 * of the air space in the lungs was 2.5±0.5 ms, which was 3.8 times shorter than that in a syringe. We developed a hyperpolarized 129 Xe experimental system using a 3T MRI scanner that yields sufficient volume and polarization and quantitatively analyzed the dissolved-phase 129 Xe signal in the rat lungs. (author)

A system for accurate and automated injection of hyperpolarized substrate with minimal dead time and scalable volumes over a large range

Science.gov (United States)

Reynolds, Steven; Bucur, Adriana; Port, Michael; Alizadeh, Tooba; Kazan, Samira M.; Tozer, Gillian M.; Paley, Martyn N. J.

2014-02-01

Over recent years hyperpolarization by dissolution dynamic nuclear polarization has become an established technique for studying metabolism in vivo in animal models. Temporal signal plots obtained from the injected metabolite and daughter products, e.g. pyruvate and lactate, can be fitted to compartmental models to estimate kinetic rate constants. Modeling and physiological parameter estimation can be made more robust by consistent and reproducible injections through automation. An injection system previously developed by us was limited in the injectable volume to between 0.6 and 2.4 ml and injection was delayed due to a required syringe filling step. An improved MR-compatible injector system has been developed that measures the pH of injected substrate, uses flow control to reduce dead volume within the injection cannula and can be operated over a larger volume range. The delay time to injection has been minimized by removing the syringe filling step by use of a peristaltic pump. For 100 μl to 10.000 ml, the volume range typically used for mice to rabbits, the average delivered volume was 97.8% of the demand volume. The standard deviation of delivered volumes was 7 μl for 100 μl and 20 μl for 10.000 ml demand volumes (mean S.D. was 9 ul in this range). In three repeat injections through a fixed 0.96 mm O.D. tube the coefficient of variation for the area under the curve was 2%. For in vivo injections of hyperpolarized pyruvate in tumor-bearing rats, signal was first detected in the input femoral vein cannula at 3-4 s post-injection trigger signal and at 9-12 s in tumor tissue. The pH of the injected pyruvate was 7.1 ± 0.3 (mean ± S.D., n = 10). For small injection volumes, e.g. less than 100 μl, the internal diameter of the tubing contained within the peristaltic pump could be reduced to improve accuracy. Larger injection volumes are limited only by the size of the receiving vessel connected to the pump.

Large dose hyperpolarized water with dissolution-DNP at high magnetic field

DEFF Research Database (Denmark)

Lipsø, Hans Kasper Wigh; Bowen, Sean; Rybalko, Oleksandr

2016-01-01

was polarized and dissolved in a fluid path compatible with clinical polarizers. The volume of hyperpolarized water produced by this method enables angiography and perfusion measurements in large animals, as well as NMR experiments for studies of e.g. proton exchange and polarization transfer to other nuclei....

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules

Directory of Open Access Journals (Sweden)

Christian Hundshammer

2018-02-01

Full Text Available pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. However, most of the known HP-sensors have only individually and not comprehensively been analyzed for their biocompatibility, their pH sensitivity under physiological conditions, and the effects of chemical derivatization on their logarithmic acid dissociation constant (pKa. Proteinogenic amino acids are biocompatible, can be hyperpolarized and have at least two pH sensitive moieties. However, they do not exhibit a pH sensitivity in the physiologically relevant pH range. Here, we developed a systematic approach to tailor the pKa of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, we identified several derivatives such as [1-13C]serine amide and [1-13C]-2,3-diaminopropionic acid as novel pH sensors. They bear several spin-1/2 nuclei (13C, 15N, 31P with high sensitivity up to 4.8 ppm/pH and we show that 13C spins can be hyperpolarized with dissolution dynamic polarization (DNP. Our findings elucidate the molecular mechanisms of chemical shift pH sensors that might help to design tailored probes for specific pH in vivo imaging applications.

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules.

Science.gov (United States)

Hundshammer, Christian; Düwel, Stephan; Ruseckas, David; Topping, Geoffrey; Dzien, Piotr; Müller, Christoph; Feuerecker, Benedikt; Hövener, Jan B; Haase, Axel; Schwaiger, Markus; Glaser, Steffen J; Schilling, Franz

2018-02-15

pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP) magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. However, most of the known HP-sensors have only individually and not comprehensively been analyzed for their biocompatibility, their pH sensitivity under physiological conditions, and the effects of chemical derivatization on their logarithmic acid dissociation constant (p K a ). Proteinogenic amino acids are biocompatible, can be hyperpolarized and have at least two pH sensitive moieties. However, they do not exhibit a pH sensitivity in the physiologically relevant pH range. Here, we developed a systematic approach to tailor the p K a of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, we identified several derivatives such as [1- 13 C]serine amide and [1- 13 C]-2,3-diaminopropionic acid as novel pH sensors. They bear several spin-1/2 nuclei ( 13 C, 15 N, 31 P) with high sensitivity up to 4.8 ppm/pH and we show that 13 C spins can be hyperpolarized with dissolution dynamic polarization (DNP). Our findings elucidate the molecular mechanisms of chemical shift pH sensors that might help to design tailored probes for specific pH in vivo imaging applications.

Seasonal Dependence of Geomagnetic Active-Time Northern High-Latitude Upper Thermospheric Winds

Science.gov (United States)

Dhadly, Manbharat S.; Emmert, John T.; Drob, Douglas P.; Conde, Mark G.; Doornbos, Eelco; Shepherd, Gordon G.; Makela, Jonathan J.; Wu, Qian; Nieciejewski, Richard J.; Ridley, Aaron J.

2018-01-01

This study is focused on improving the poorly understood seasonal dependence of northern high-latitude F region thermospheric winds under active geomagnetic conditions. The gaps in our understanding of the dynamic high-latitude thermosphere are largely due to the sparseness of thermospheric wind measurements. With current observational facilities, it is infeasible to construct a synoptic picture of thermospheric winds, but enough data with wide spatial and temporal coverage have accumulated to construct a meaningful statistical analysis. We use long-term data from eight ground-based and two space-based instruments to derive climatological wind patterns as a function of magnetic local time, magnetic latitude, and season. These diverse data sets possess different geometries and different spatial and solar activity coverage. The major challenge is to combine these disparate data sets into a coherent picture while overcoming the sampling limitations and biases among them. In our previous study (focused on quiet time winds), we found bias in the Gravity Field and Steady State Ocean Circulation Explorer (GOCE) cross-track winds. Here we empirically quantify the GOCE bias and use it as a correction profile for removing apparent bias before empirical wind formulation. The assimilated wind patterns exhibit all major characteristics of high-latitude neutral circulation. The latitudinal extent of duskside circulation expands almost 10∘ from winter to summer. The dawnside circulation subsides from winter to summer. Disturbance winds derived from geomagnetic active and quiet winds show strong seasonal and latitudinal variability. Comparisons between wind patterns derived here and Disturbance Wind Model (DWM07) (which have no seasonal dependence) suggest that DWM07 is skewed toward summertime conditions.

Hyperpolarized ¹³C Urea Relaxation Mechanism Reveals Renal Changes in Diabetic Nephropathy

DEFF Research Database (Denmark)

Laustsen, Christoffer; Stokholm Nørlinger, Thomas; Christoffer Hansen, David

2016-01-01

Purpose: Our aim was to assess a novel 13C radial fast spin echo golden ratio single shot method for interrogating early renal changes in the diabetic kidney, using hyperpolarized (HP) [13C,15N2]urea as a T2 relaxation based contrast bio-probe. Methods: A novel HP 13C MR contrast experiment...... saturation level and the relaxation times were observed in the healthy controls. Conclusion: HP [13C,15N2]urea apparent T2 mapping may be a useful for interrogating local renal pO2 status and renal tissue alterations....

Direct hyperpolarization of micro- and nanodiamonds for bioimaging applications - Considerations on particle size, functionalization and polarization loss.

Science.gov (United States)

Kwiatkowski, Grzegorz; Jähnig, Fabian; Steinhauser, Jonas; Wespi, Patrick; Ernst, Matthias; Kozerke, Sebastian

2018-01-01

Due to the inherently long relaxation time of 13 C spins in diamond, the nuclear polarization enhancement obtained with dynamic nuclear polarization can be preserved for a time on the order of about one hour, opening up an opportunity to use diamonds as a new class of long-lived contrast agents. The present communication explores the feasibility of using 13 C spins in directly hyperpolarized diamonds for MR imaging including considerations for potential in vivo applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of an inward rectifier K+ current and of hyperpolarization in human myoblast fusion

Science.gov (United States)

Liu, J-H; Bijlenga, P; Fischer-Lougheed, J; Occhiodoro, T; Kaelin, A; Bader, C R; Bernheim, L

1998-01-01

The role of K+ channels and membrane potential in myoblast fusion was evaluated by examining resting membrane potential and timing of expression of K+ currents at three stages of differentiation of human myogenic cells: undifferentiated myoblasts, fusion-competent myoblasts (FCMBs), and freshly formed myotubes. Two K+ currents contribute to a hyperpolarization of myoblasts prior to fusion: IK(NI), a non-inactivating delayed rectifier, and IK(IR), an inward rectifier. IK(NI) density is low in undifferentiated myoblasts, increases in FCMBs and declines in myotubes. On the other hand, IK(IR) is expressed in 28 % of the FCMBs and in all myotubes. IK(IR) is reversibly blocked by Ba2+ or Cs+. Cells expressing IK(IR) have resting membrane potentials of −65 mV. A block by Ba2+ or Cs+ induces a depolarization to a voltage determined by IK(NI) (−32 mV). Cs+ and Ba2+ ions reduce myoblast fusion. It is hypothesized that the IK(IR)-mediated hyperpolarization allows FCMBs to recruit Na+, K+ and T-type Ca2+ channels which are present in these cells and would otherwise be inactivated. FCMBs, rendered thereby capable of firing action potentials, could amplify depolarizing signals and may accelerate fusion. PMID:9705997

Influence of washing time on residual contamination of carcasses sprayed with lauric acid-potassium hydroxide.

Science.gov (United States)

A series of experiments were conducted to examine reductions in bacterial contamination of broiler carcasses washed for various times in a spray cabinet with a 2% lauric acid (LA)-1% potassium hydroxide (KOH) (w/v) solution. Forty eviscerated carcasses and 5 ceca were obtained from the processing l...

Dielectric properties of a potassium nitrate–ammonium nitrate system

OpenAIRE

Alexey Yu. Milinskiy; Anton A. Antonov

2015-01-01

Potassium nitrate has a rectangular hysteresis loop and is thought to be a promising material for non-volatile ferroelectric memory. However, its polar phase is observed in a narrow temperature range. This paper deals with an effect of ammonium nitrate NH4NO3 on the dielectric properties of potassium nitrate. Thermal dependencies of the linear dielectric permittivity ε and the third-harmonic coefficient g3 for potassium nitrate and polycrystalline binary (KNO3)1–x(NH4NO3)x system (x = 0.025, ...

[Effects of vitamin K3 on the contractile activity of the colonic smooth muscles of guinea pig through the calcium activated potassium channel].

Science.gov (United States)

Li, Jun; Luo, He-sheng; He, Xiao-gu

2006-07-25

To study the mechanism of relaxation of gastrointestinal smooth muscles by vitamin K(3). Stripes of proximal colon were collected from guinea pigs. Suspension of single cells was created from these stripes. TD-112S transducer was used to measure the contraction of the stripes stimulated by vitamin K(3) of the concentrations of 40, 100, 400, and 800 micromol/L respectively. The Ca(2+)-activated K(+) current [IK(Ca)] of the cytomembrane of the colon smooth muscle was recorded with an EPC 10 amplifier under conventional whole cell patterns. The contraction frequencies of the muscle stripes stimulated by vitamin K(3) of the concentrations of 40, 100, 400, and 800 micromol/L were 79% +/- 4%, 58% +/- 5%, 33% +/- 4%, and 12% +/- 3% respectively of that of the control group (all P Vitamin K(3) inhibits the contractile activity of the colonic muscle stripes and increases the IK(Ca) of single myocytes concentration-dependently. The mechanism is activation of the Ca(2+)-activated K(+) channel, thus promoting the potassium efflux.

A Duo of Potassium-Responsive Histidine Kinases Govern the Multicellular Destiny of Bacillus subtilis.

Science.gov (United States)

Grau, Roberto R; de Oña, Paula; Kunert, Maritta; Leñini, Cecilia; Gallegos-Monterrosa, Ramses; Mhatre, Eisha; Vileta, Darío; Donato, Verónica; Hölscher, Theresa; Boland, Wilhelm; Kuipers, Oscar P; Kovács, Ákos T

2015-07-07

Multicellular biofilm formation and surface motility are bacterial behaviors considered mutually exclusive. However, the basic decision to move over or stay attached to a surface is poorly understood. Here, we discover that in Bacillus subtilis, the key root biofilm-controlling transcription factor Spo0A~Pi (phosphorylated Spo0A) governs the flagellum-independent mechanism of social sliding motility. A Spo0A-deficient strain was totally unable to slide and colonize plant roots, evidencing the important role that sliding might play in natural settings. Microarray experiments plus subsequent genetic characterization showed that the machineries of sliding and biofilm formation share the same main components (i.e., surfactin, the hydrophobin BslA, exopolysaccharide, and de novo-formed fatty acids). Sliding proficiency was transduced by the Spo0A-phosphorelay histidine kinases KinB and KinC. We discovered that potassium, a previously known inhibitor of KinC-dependent biofilm formation, is the specific sliding-activating signal through a thus-far-unnoticed cytosolic domain of KinB, which resembles the selectivity filter sequence of potassium channels. The differential expression of the Spo0A~Pi reporter abrB gene and the different levels of the constitutively active form of Spo0A, Sad67, in Δspo0A cells grown in optimized media that simultaneously stimulate motile and sessile behaviors uncover the spatiotemporal response of KinB and KinC to potassium and the gradual increase in Spo0A~Pi that orchestrates the sequential activation of sliding, followed by sessile biofilm formation and finally sporulation in the same population. Overall, these results provide insights into how multicellular behaviors formerly believed to be antagonistic are coordinately activated in benefit of the bacterium and its interaction with the host. Alternation between motile and sessile behaviors is central to bacterial adaptation, survival, and colonization. However, how is the collective

Ex vivo hyperpolarized MR spectroscopy on isolated renal tubular cells: A novel technique for cell energy phenotyping.

Science.gov (United States)

Juul, Troels; Palm, Fredrik; Nielsen, Per Mose; Bertelsen, Lotte Bonde; Laustsen, Christoffer

2017-08-01

It has been demonstrated that hyperpolarized 13 C MR is a useful tool to study cultured cells. However, cells in culture can alter phenotype, which raises concerns regarding the in vivo significance of such findings. Here we investigate if metabolic phenotyping using hyperpolarized 13 C MR is suitable for cells isolated from kidney tissue, without prior cell culture. Isolation of tubular cells from freshly excised kidney tissue and treatment with either ouabain or antimycin A was investigated with hyperpolarized MR spectroscopy on a 9.4 Tesla preclinical imaging system. Isolation of tubular cells from less than 2 g of kidney tissue generally resulted in more than 10 million live tubular cells. This amount of cells was enough to yield robust signals from the conversion of 13 C-pyruvate to lactate, bicarbonate and alanine, demonstrating that metabolic flux by means of both anaerobic and aerobic pathways can be quantified using this technique. Ex vivo metabolic phenotyping using hyperpolarized 13 C MR in a preclinical system is a useful technique to study energy metabolism in freshly isolated renal tubular cells. This technique has the potential to advance our understanding of both normal cell physiology as well as pathological processes contributing to kidney disease. Magn Reson Med 78:457-461, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Plant adaptation to fluctuating environment and biomass production are strongly dependent on guard cell potassium channels

Science.gov (United States)

Lebaudy, Anne; Vavasseur, Alain; Hosy, Eric; Dreyer, Ingo; Leonhardt, Nathalie; Thibaud, Jean-Baptiste; Véry, Anne-Aliénor; Simonneau, Thierry; Sentenac, Hervé

2008-01-01

At least four genes encoding plasma membrane inward K+ channels (Kin channels) are expressed in Arabidopsis guard cells. A double mutant plant was engineered by disruption of a major Kin channel gene and expression of a dominant negative channel construct. Using the patch-clamp technique revealed that this mutant was totally deprived of guard cell Kin channel (GCKin) activity, providing a model to investigate the roles of this activity in the plant. GCKin activity was found to be an essential effector of stomatal opening triggered by membrane hyperpolarization and thereby of blue light-induced stomatal opening at dawn. It improved stomatal reactivity to external or internal signals (light, CO2 availability, and evaporative demand). It protected stomatal function against detrimental effects of Na+ when plants were grown in the presence of physiological concentrations of this cation, probably by enabling guard cells to selectively and rapidly take up K+ instead of Na+ during stomatal opening, thereby preventing deleterious effects of Na+ on stomatal closure. It was also shown to be a key component of the mechanisms that underlie the circadian rhythm of stomatal opening, which is known to gate stomatal responses to extracellular and intracellular signals. Finally, in a meteorological scenario with higher light intensity during the first hours of the photophase, GCKin activity was found to allow a strong increase (35%) in plant biomass production. Thus, a large diversity of approaches indicates that GCKin activity plays pleiotropic roles that crucially contribute to plant adaptation to fluctuating and stressing natural environments. PMID:18367672

Immunomodulatory effects of diclofenac in leukocytes through the targeting of Kv1.3 voltage-dependent potassium channels.

Science.gov (United States)

Villalonga, Núria; David, Miren; Bielańska, Joanna; González, Teresa; Parra, David; Soler, Concepció; Comes, Núria; Valenzuela, Carmen; Felipe, Antonio

2010-09-15

Kv1.3 plays a crucial role in the activation and proliferation of T-lymphocytes and macrophages. While Kv1.3 is responsible for the voltage-dependent potassium current in T-cells, in macrophages this K(+) current is generated by the association of Kv1.3 and Kv1.5. Patients with autoimmune diseases show a high number of effector memory T cells that are characterized by a high expression of Kv1.3 and Kv1.3 antagonists ameliorate autoimmune disorders in vivo. Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used in patients who suffer from painful autoimmune diseases such as rheumatoid arthritis. In this study, we show that diclofenac impairs immune response via a mechanism that involves Kv1.3. While diclofenac inhibited Kv1.3 expression in activated macrophages and T-lymphocytes, Kv1.5 remained unaffected. Diclofenac also decreased iNOS levels in Raw 264.7 cells, impairing their activation in response to lipopolysaccharide (LPS). LPS-induced macrophage migration and IL-2 production in stimulated Jurkat T-cells were also blocked by pharmacological doses of diclofenac. These effects were mimicked by Margatoxin, a specific Kv1.3 inhibitor, and Charybdotoxin, which blocks both Kv1.3 and Ca(2+)-activated K(+) channels (K(Ca)3.1). Because Kv1.3 is a very good target for autoimmune therapies, the effects of diclofenac on Kv1.3 are of high pharmacological relevance. Copyright 2010 Elsevier Inc. All rights reserved.

Hyperpolarized 13C MR imaging detects no lactate production in mutant IDH1 gliomas: Implications for diagnosis and response monitoring

Directory of Open Access Journals (Sweden)

Myriam M. Chaumeil

2016-01-01

Full Text Available Metabolic imaging of brain tumors using 13C Magnetic Resonance Spectroscopy (MRS of hyperpolarized [1-13C] pyruvate is a promising neuroimaging strategy which, after a decade of preclinical success in glioblastoma (GBM models, is now entering clinical trials in multiple centers. Typically, the presence of GBM has been associated with elevated hyperpolarized [1-13C] lactate produced from [1-13C] pyruvate, and response to therapy has been associated with a drop in hyperpolarized [1-13C] lactate. However, to date, lower grade gliomas had not been investigated using this approach. The most prevalent mutation in lower grade gliomas is the isocitrate dehydrogenase 1 (IDH1 mutation, which, in addition to initiating tumor development, also induces metabolic reprogramming. In particular, mutant IDH1 gliomas are associated with low levels of lactate dehydrogenase A (LDHA and monocarboxylate transporters 1 and 4 (MCT1, MCT4, three proteins involved in pyruvate metabolism to lactate. We therefore investigated the potential of 13C MRS of hyperpolarized [1-13C] pyruvate for detection of mutant IDH1 gliomas and for monitoring of their therapeutic response. We studied patient-derived mutant IDH1 glioma cells that underexpress LDHA, MCT1 and MCT4, and wild-type IDH1 GBM cells that express high levels of these proteins. Mutant IDH1 cells and tumors produced significantly less hyperpolarized [1-13C] lactate compared to GBM, consistent with their metabolic reprogramming. Furthermore, hyperpolarized [1-13C] lactate production was not affected by chemotherapeutic treatment with temozolomide (TMZ in mutant IDH1 tumors, in contrast to previous reports in GBM. Our results demonstrate the unusual metabolic imaging profile of mutant IDH1 gliomas, which, when combined with other clinically available imaging methods, could be used to detect the presence of the IDH1 mutation in vivo.

Rearrangement of potassium ions and Kv1.1/Kv1.2 potassium channels in regenerating axons following end-to-end neurorrhaphy: ionic images from TOF-SIMS.

Science.gov (United States)

Liu, Chiung-Hui; Chang, Hung-Ming; Wu, Tsung-Huan; Chen, Li-You; Yang, Yin-Shuo; Tseng, To-Jung; Liao, Wen-Chieh

2017-10-01

The voltage-gated potassium channels Kv1.1 and Kv1.2 that cluster at juxtaparanodal (JXP) regions are essential in the regulation of nerve excitability and play a critical role in axonal conduction. When demyelination occurs, Kv1.1/Kv1.2 activity increases, suppressing the membrane potential nearly to the equilibrium potential of K + , which results in an axonal conduction blockade. The recovery of K + -dependent communication signals and proper clustering of Kv1.1/Kv1.2 channels at JXP regions may directly reflect nerve regeneration following peripheral nerve injury. However, little is known about potassium channel expression and its relationship with the dynamic potassium ion distribution at the node of Ranvier during the regenerative process of peripheral nerve injury (PNI). In the present study, end-to-end neurorrhaphy (EEN) was performed using an in vivo model of PNI. The distribution of K + at regenerating axons following EEN was detected by time-of-flight secondary-ion mass spectrometry. The specific localization and expression of Kv1.1/Kv1.2 channels were examined by confocal microscopy and western blotting. Our data showed that the re-establishment of K + distribution and intensity was correlated with the functional recovery of compound muscle action potential morphology in EEN rats. Furthermore, the re-clustering of Kv1.1/1.2 channels 1 and 3 months after EEN at the nodal region of the regenerating nerve corresponded to changes in the K + distribution. This study provided direct evidence of K + distribution in regenerating axons for the first time. We proposed that the Kv1.1/Kv1.2 channels re-clustered at the JXP regions of regenerating axons are essential for modulating the proper patterns of K + distribution in axons for maintaining membrane potential stability after EEN.

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…

Age and sex dependence of body potassium based on studies of 40K under Indian conditions

International Nuclear Information System (INIS)

Ranganathan, S.; Someswara Rao, M.; Nagaratnam, A.; Mishra, U.C.

2002-01-01

Potassium plays an important role in human life 40 K is a naturally occurring radioisotope of potassium (K) with an abundance of 0.0118%. The measurement of body 40 K in a whole-body counter (WBC) provides a sensitive technique to estimate the total body potassium (TBK). Information on TBK of Indians with age and sex is scanty. Therefore, a systematic study was taken up to generate this information using a sensitive WBC

Benign and efficient preparation of thioethers by solvent-free S-alkylation of thiols with alkyl halides catalyzed by potassium fluoride on alumina

DEFF Research Database (Denmark)

Nguyen, Kha Ngoc; Duus, Fritz; Luu, Thi Xuan Thi

2016-01-01

The preparation of thioethers by S-alkylation of various thiols with alkyl halides under solvent-free reaction conditions using potassium fluoride on alumina (KF/Al2O3) as a solid catalyst has been investigated in detail with respect to three different modes of reaction activation (ultrasound...... irradiation, microwave irradiation, and conventional heating) for obtaining maximum yield of the thioether. The importance of KF/Al2O3 as a particularly efficient catalyst was corroborated for all three modes of reaction activation, although the reaction time was found to be strongly dependent on the mode...

Low Potassium (Hypokalemia)

Science.gov (United States)

Symptoms Low potassium (hypokalemia) By Mayo Clinic Staff Low potassium (hypokalemia) refers to a lower than normal potassium level ... 2 millimoles per liter (mmol/L). A very low potassium level (less than 2.5 mmol/L) ...

Time-dependent Hartree approximation and time-dependent harmonic oscillator model

International Nuclear Information System (INIS)

Blaizot, J.P.

1982-01-01

We present an analytically soluble model for studying nuclear collective motion within the framework of the time-dependent Hartree (TDH) approximation. The model reduces the TDH equations to the Schroedinger equation of a time-dependent harmonic oscillator. Using canonical transformations and coherent states we derive a few properties of the time-dependent harmonic oscillator which are relevant for applications. We analyse the role of the normal modes in the time evolution of a system governed by TDH equations. We show how these modes couple together due to the anharmonic terms generated by the non-linearity of the theory. (orig.)

Kidney in potassium depletion. II. K+ handling by the isolated perfused rat kidney

International Nuclear Information System (INIS)

Hayashi, M.; Katz, A.I.

1987-01-01

In a companion paper the authors reported a large increment in Na + -K + -ATPase activity and [ 3 H]ouabain binding the inner stripe of outer medullary collecting tubules from K-depleted rats. To test the hypothesis that the increased number of Na + -K + pumps in these animals may be involved in potassium reabsorption they examined the effect of ouabain on K excretion by isolated, perfused kidneys from rats fed a K-free diet for 3 wk. Kidneys from K-depleted rats retain potassium avidly, both the fractional (FE/sub K/) and absolute K excretion being approximately fivefold lower than in control kidneys. Ouabain (5 mM) increased FE/sub K/ in kidneys from each K-depleted rat; similar results were obtained when kidneys were perfused with low and high potassium concentrations. In contrast, ouabain produced a variable effect in control kidneys, that depended on the perfusate potassium concentration. In K-depleted rats amiloride did not significantly alter K excretion and did not block the ouabain-induced kaliuresis, suggesting that the latter is not due to enhanced secretion secondary to increased distal fluid delivery. These results provide evidence for ouabain-sensitive potassium reabsorption in kidneys of chronically K-depleted rats, and suggest an explanation for the increased Na + -K + -ATPase observed in such animals

Simultaneous hyperpolarized ¹³C-pyruvate MRI and ¹⁸F-FDG-PET in cancer (hyperPET)

DEFF Research Database (Denmark)

Borgwardt, Henrik Gutte; Hansen, Adam Espe; Henriksen, Sarah T.

2015-01-01

have named this concept hyper PET. Intravenous injection of the hyperpolarized (13)C-pyruvate results in an increase of (13)C-lactate, (13)C-alanine and (13)C-CO2 ((13)C-HCO3) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization......In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and (18)F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We...... (DNP) and use of (13)C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of (13)C-pyruvate to (13)C-lactate. In this study, we combined it with (18)F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified...

Effects of superparamagnetic iron oxide nanoparticles on the longitudinal and transverse relaxation of hyperpolarized xenon gas

Science.gov (United States)

Burant, Alex; Antonacci, Michael; McCallister, Drew; Zhang, Le; Branca, Rosa Tamara

2018-06-01

SuperParamagnetic Iron Oxide Nanoparticles (SPIONs) are often used in magnetic resonance imaging experiments to enhance Magnetic Resonance (MR) sensitivity and specificity. While the effect of SPIONs on the longitudinal and transverse relaxation time of 1H spins has been well characterized, their effect on highly diffusive spins, like those of hyperpolarized gases, has not. For spins diffusing in linear magnetic field gradients, the behavior of the magnetization is characterized by the relative size of three length scales: the diffusion length, the structural length, and the dephasing length. However, for spins diffusing in non-linear gradients, such as those generated by iron oxide nanoparticles, that is no longer the case, particularly if the diffusing spins experience the non-linearity of the gradient. To this end, 3D Monte Carlo simulations are used to simulate the signal decay and the resulting image contrast of hyperpolarized xenon gas near SPIONs. These simulations reveal that signal loss near SPIONs is dominated by transverse relaxation, with little contribution from T1 relaxation, while simulated image contrast and experiments show that diffusion provides no appreciable sensitivity enhancement to SPIONs.

Evaluating the effect of potassium on cellulose pyrolysis reaction kinetics

International Nuclear Information System (INIS)

Trendewicz, Anna; Evans, Robert; Dutta, Abhijit; Sykes, Robert; Carpenter, Daniel; Braun, Robert

2015-01-01

This paper proposes modifications to an existing cellulose pyrolysis mechanism in order to include the effect of potassium on product yields and composition. The changes in activation energies and pre-exponential factors due to potassium were evaluated based on the experimental data collected from pyrolysis of cellulose samples treated with different levels of potassium (0–1% mass fraction). The experiments were performed in a pyrolysis reactor coupled to a molecular beam mass spectrometer (MBMS). Principal component analysis (PCA) performed on the collected data revealed that cellulose pyrolysis products could be divided into two groups: anhydrosugars and other fragmentation products (hydroxyacetaldehyde, 5-hydroxymethylfurfural, acetyl compounds). Multivariate curve resolution (MCR) was used to extract the time resolved concentration score profiles of principal components. Kinetic tests revealed that potassium apparently inhibits the formation of anhydrosugars and catalyzes char formation. Therefore, the oil yield predicted at 500 ° C decreased from 87.9% from cellulose to 54.0% from cellulose with 0.5% mass fraction potassium treatment. The decrease in oil yield was accompanied by increased yield of char and gases produced via a catalyzed dehydration reaction. The predicted char and gas yield from cellulose were 3.7% and 8.4%, respectively. Introducing 0.5% mass fraction potassium treatment resulted in an increase of char yield to 12.1% and gas yield to 33.9%. The validation of the cellulose pyrolysis mechanism with experimental data from a fluidized-bed reactor, after this correction for potassium, showed good agreement with our results, with differences in product yields of up to 5%

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-07-29

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

The role of hyperpolarized {sup 129}xenon in MR imaging of pulmonary function

Energy Technology Data Exchange (ETDEWEB)

Ebner, Lukas [Cardiothoracic Imaging, Duke University Medical Center, Department of Radiology, Duke University, Durham, NC (United States); Kammerman, Jeff [Department of Medical Physics, University of Wisconsin, Madison, WI (United States); Driehuys, Bastiaan [Center for In Vivo Microscopy, Duke University, Durham, NC (United States); Schiebler, Mark L. [Department of Radiology, University of Wisconsin, Madison, WI (United States); Cadman, Robert V. [Department of Medical Physics, University of Wisconsin, Madison, WI (United States); Fain, Sean B., E-mail: sfain@wisc.edu [Departments of Medical Physics, Radiology, and Biomedical Engineering, University of Wisconsin, Madison, WI (United States)

2017-01-15

Highlights: • Recent advances in hyperpolarized 129Xe MRI are reviewed. • Xenon MRI allows for functional imaging of ventilation, diffusion, and gas exchange. • Xenon’s unique gas exchange imaging capabilities are highlighted. • Applications to obstructive and restrictive lung diseases are presented. • These advances are ready for translation to clinical applications. - Abstract: In the last two decades, functional imaging of the lungs using hyperpolarized noble gases has entered the clinical stage. Both helium ({sup 3}He) and xenon ({sup 129}Xe) gas have been thoroughly investigated for their ability to assess both the global and regional patterns of lung ventilation. With advances in polarizer technology and the current transition towards the widely available {sup 129}Xe gas, this method is ready for translation to the clinic. Currently, hyperpolarized (HP) noble gas lung MRI is limited to selected academic institutions; yet, the promising results from initial clinical trials have drawn the attention of the pulmonary medicine community. HP {sup 129}Xe MRI provides not only 3-dimensional ventilation imaging, but also unique capabilities for probing regional lung physiology. In this review article, we aim to (1) provide a brief overview of current ventilation MR imaging techniques, (2) emphasize the role of HP {sup 129}Xe MRI within the array of different imaging strategies, (3) discuss the unique imaging possibilities with HP {sup 129}Xe MRI, and (4) propose clinical applications.

CAMKII activation is not required for maintenance of learning-induced enhancement of neuronal excitability.

Directory of Open Access Journals (Sweden)

Ori Liraz

Full Text Available Pyramidal neurons in the piriform cortex from olfactory-discrimination trained rats show enhanced intrinsic neuronal excitability that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the post-burst after-hyperpolarization (AHP which is generated by repetitive spike firing. AHP reduction is due to decreased conductance of a calcium-dependent potassium current, the sI(AHP. We have previously shown that learning-induced AHP reduction is maintained by persistent protein kinase C (PKC and extracellular regulated kinase (ERK activation. However, the molecular machinery underlying this long-lasting modulation of intrinsic excitability is yet to be fully described. Here we examine whether the CaMKII, which is known to be crucial in learning, memory and synaptic plasticity processes, is instrumental for the maintenance of learning-induced AHP reduction. KN93, that selectively blocks CaMKII autophosphorylation at Thr286, reduced the AHP in neurons from trained and control rat to the same extent. Consequently, the differences in AHP amplitude and neuronal adaptation between neurons from trained rats and controls remained. Accordingly, the level of activated CaMKII was similar in pirifrom cortex samples taken form trained and control rats. Our data show that although CaMKII modulates the amplitude of AHP of pyramidal neurons in the piriform cortex, its activation is not required for maintaining learning-induced enhancement of neuronal excitability.

Mechanism of cesium sorption on potassium titanium hexacyanoferrate

International Nuclear Information System (INIS)

Sun Yongxia; Xu Shiping; Song Chongli

1998-01-01

The mechanism of cesium sorption on potassium titanium hexacyanoferrate is described. The dependence of the sorption speed on temperature, particle granule size, and the stirring speed is studied. The results show that the sorption process is controlled by liquid film diffusion and particle diffusion. An exchange reaction occurs mainly between K + in the exchanger and Cs + in the solution, i.e. potassium titanium hexacyanoferrate, and Cs + of simulated high-level liquid waste

Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals

DEFF Research Database (Denmark)

Bastiaansen, Jessica A M; Yoshihara, Hikari A I; Capozzi, Andrea

2018-01-01

dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. Ultraviolet irradiation created nonpersistent radicals in a mixture containing......To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13 C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. Droplets of mixed [1-13 C]pyruvic and [1-13 C]butyric acids were frozen...... into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were...

Urinary potassium to urinary potassium plus sodium ratio can accurately identify hypovolemia in nephrotic syndrome: a provisional study.

Science.gov (United States)

Keenswijk, Werner; Ilias, Mohamad Ikram; Raes, Ann; Donckerwolcke, Raymond; Walle, Johan Vande

2018-01-01

There is evidence pointing to a decrease of the glomerular filtration rate (GFR) in a subgroup of nephrotic children, likely secondary to hypovolemia. The aim of this study is to validate the use of urinary potassium to the sum of potassium plus sodium ratio (UK/UK+UNa) as an indicator of hypovolemia in nephrotic syndrome, enabling detection of those patients who will benefit from albumin infusion. We prospectively studied 44 nephrotic children and compared different parameters to a control group (36 children). Renal perfusion and glomerular permeability were assessed by measuring clearance of para-aminohippurate and inulin. Vaso-active hormones and urinary sodium and potassium were also measured. Subjects were grouped into low, normal, and high GFR groups. In the low GFR group, significantly lower renal plasma flow (p = 0.01), filtration fraction (p = 0.01), and higher UK/UK+UNa (p = 0.03) ratio were noted. In addition, non-significant higher plasma renin activity (p = 0.11) and aldosteron (p = 0.09) were also seen in the low GFR group. A subgroup of patients in nephrotic syndrome has a decrease in glomerular filtration, apparently related to hypovolemia which likely can be detected by a urinary potassium to potassium plus sodium ratio > 0.5-0.6 suggesting benefit of albumin infusion in this subgroup. What is Known: • Volume status can be difficult to assess based on clinical parameters in nephrotic syndrome, and albumin infusion can be associated with development of pulmonary edema and fluid overload in these patients. What is New: • Urinary potassium to the sum of urinary potassium plus sodium ratio can accurately detect hypovolemia in nephrotic syndrome and thus identify those children who would probably respond to albumin infusion.

Effects of cisplatin on potassium currents in CT26 cells

Directory of Open Access Journals (Sweden)

Naveen Sharma

2016-01-01

Conclusion: Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192< by the application of cisplatin (0.5 mM. Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells.

NO involvement in the inhibition of ghrelin on voltage-dependent potassium currents in rat hippocampal cells.

Science.gov (United States)

Lu, Yong; Dang, Shaokang; Wang, Xu; Zhang, Junli; Zhang, Lin; Su, Qian; Zhang, Huiping; Lin, Tianwei; Zhang, Xiaoxiao; Zhang, Yurong; Sun, Hongli; Zhu, Zhongliang; Li, Hui

2018-01-01

Ghrelin is a peptide hormone that plays an important role in promoting appetite, regulating distribution and rate of use of energy, cognition, and mood disorders, but the relevant neural mechanisms of these function are still not clear. In this study, we examined the effect of ghrelin on voltage-dependent potassium (K + ) currents in hippocampal cells of 1-3 days SD rats by whole-cell patch-clamp technique, and discussed whether NO was involved in this process. The results showed that ghrelin significantly inhibited the voltage-dependent K + currents in hippocampal cells, and the inhibitory effect was more significant when l-arginine was co-administered. In contrast, N-nitro- l-arginine methyl ester increased the ghrelin inhibited K + currents and attenuated the inhibitory effect of ghrelin. While d-arginine (D-AA) showed no significant impact on the ghrelin-induced decrease in K + current. These results show that ghrelin may play a physiological role by inhibiting hippocampal voltage dependent K + currents, and the NO pathway may be involved in this process. Copyright © 2017 Elsevier B.V. All rights reserved.

Time-dependent embedding

OpenAIRE

Inglesfield, J. E.

2007-01-01

A method of solving the time-dependent Schr\\"odinger equation is presented, in which a finite region of space is treated explicitly, with the boundary conditions for matching the wave-functions on to the rest of the system replaced by an embedding term added on to the Hamiltonian. This time-dependent embedding term is derived from the Fourier transform of the energy-dependent embedding potential, which embeds the time-independent Schr\\"odinger equation. Results are presented for a one-dimensi...

Quantified pH imaging with hyperpolarized (13) C-bicarbonate.

Science.gov (United States)

Scholz, David Johannes; Janich, Martin A; Köllisch, Ulrich; Schulte, Rolf F; Ardenkjaer-Larsen, Jan H; Frank, Annette; Haase, Axel; Schwaiger, Markus; Menzel, Marion I

2015-06-01

Because pH plays a crucial role in several diseases, it is desirable to measure pH in vivo noninvasively and in a spatially localized manner. Spatial maps of pH were quantified in vitro, with a focus on method-based errors, and applied in vivo. In vitro and in vivo (13) C mapping were performed for various flip angles for bicarbonate (BiC) and CO2 with spectral-spatial excitation and spiral readout in healthy Lewis rats in five slices. Acute subcutaneous sterile inflammation was induced with Concanavalin A in the right leg of Buffalo rats. pH and proton images were measured 2 h after induction. After optimizing the signal to noise ratio of the hyperpolarized (13) C-bicarbonate, error estimation of the spectral-spatial excited spectrum reveals that the method covers the biologically relevant pH range of 6 to 8 with low pH error (< 0.2). Quantification of pH maps shows negligible impact of the residual bicarbonate signal. pH maps reflect the induction of acute metabolic alkalosis. Inflamed, infected regions exhibit lower pH. Hyperpolarized (13) C-bicarbonate pH mapping was shown to be sensitive in the biologically relevant pH range. The mapping of pH was applied to healthy in vivo organs and interpreted within inflammation and acute metabolic alkalosis models. © 2014 Wiley Periodicals, Inc.

Alkali activated fly ash binders. A comparative study between sodium and potassium activators

Directory of Open Access Journals (Sweden)

Criado, M.

2006-03-01

Full Text Available This paper shows the effect of the nature of some alkaline activators in the microstructural development of thermal-alkali activated f/y ash systems. The alkaline compounds employed in this investigation were: NaOH, KOH, Na2C03, K2C03, sodium silicate and potassium silicate. Results confirm that the main reaction product of the activation process (throughout the studied systems is the amorphous alkaline aluminosilicate gel with a three-dimensional structure already observed in earlier research. It has been proved that the type of anion and cation involved in the activation reaction of the ashes not only affects the microstructural development of the systems but the Si/Al ratio of that prezeolitic gel too. For example, in the presence of soluble silicate ions the content of Si in the final structure is notably increased (Si/Al =2.7-3.0, however carbonate ions play a different role since the formation of Sodium or Potassium carbonate/bicarbonate acidifies the system and consequently the reaction rate is considerably slowed. Finally it is evident that; when all experimental conditions are equal, sodium has a greater capacity than potassium to accelerate the setting and hardening reactions of fly ash and also to stimulate the growth of certain zeolitic crystals (reaction by-products. In general it can be affirmed that OH- ion acts as a reaction catalyst; and the alkaline metal (M+ acts as a structure-forming element.Este trabajo muestra el efecto de la naturaleza del activador alcalino en el desarrollo microestructural de sistemas de ceniza volante, activados térmica y alcalinamente. Los componentes alcalinos empleados en esta investigación fueron: NaOH, KOH, Na2C03, K2C03, silicato sódico y silicato potásico. Los resultados obtenidos confirman que el principal producto de reacción del proceso de activación (a través de los sistemas estudiados es un gel de aluminosilicato alcalino amorfo con estructura tridimensional ya observada en trabajos

Influence of biochar application on potassium-solubilizing Bacillus mucilaginosus as potential biofertilizer.

Science.gov (United States)

Liu, Sainan; Tang, Wenzhu; Yang, Fan; Meng, Jun; Chen, Wenfu; Li, Xianzhen

2017-01-02

Biochar can enhance soil fertility to increase agricultural productivity, whereas its improvement in soil microbial activity is still unclear. In this article, the influence of biochar on the cell growth and the potassium-solubilizing activity of Bacillus mucilaginosus AS1153 was examined. The impact on cell growth is related to the biochar-derived feedstocks and the particle size of biochar. Both intrinsic features and inner component fraction can promote the cell growth of B. mucilaginosus AS1153. The potassium-solubilizing activity was increased by 80% when B. mucilaginosus was incubated in conjunction with the biochar derived from corn stover. The survival time of B. mucilaginosus also was prolonged by adsorption in biochar. The experimental results suggested that the biochar containing B. mucilaginosus could be used as a potential biofertilizer to sustain crop production.

Passive shimming of the fringe field of a superconducting magnet for ultra-low field hyperpolarized noble gas MRI.

Science.gov (United States)

Parra-Robles, Juan; Cross, Albert R; Santyr, Giles E

2005-05-01

Hyperpolarized noble gases (HNGs) provide exciting possibilities for MR imaging at ultra-low magnetic field strengths (superconductive magnets used in clinical MR imaging can provide a stable magnetic field for this purpose. In addition to offering the benefit of HNG MR imaging alongside conventional high field proton MRI, this approach offers the other useful advantage of providing different field strengths at different distances from the magnet. However, the extremely strong field gradients associated with the fringe field present a major challenge for imaging since impractically high active shim currents would be required to achieve the necessary homogeneity. In this work, a simple passive shimming method based on the placement of a small number of ferromagnetic pieces is proposed to reduce the fringe field inhomogeneities to a level that can be corrected using standard active shims. The method explicitly takes into account the strong variations of the field over the volume of the ferromagnetic pieces used to shim. The method is used to obtain spectra in the fringe field of a high-field (1.89 T) superconducting magnet from hyperpolarized 129Xe gas samples at two different ultra-low field strengths (8.5 and 17 mT). The linewidths of spectra measured from imaging phantoms (30 Hz) indicate a homogeneity sufficient for MRI of the rat lung.

Reproducibility of Serum Potassium Values in Serum From Blood Samples Stored for Increasing Times Prior to Centrifugation and Analysis.

Science.gov (United States)

Harper, Aaron; Lu, Chuanyong; Sun, Yi; Garcia, Rafael; Rets, Anton; Alexis, Herol; Saad, Heba; Eid, Ikram; Harris, Loretta; Marshall, Barbara; Tafani, Edlira; Pincus, Matthew R

2016-05-01

The goal of this work was to determine if immediate versus postponed centrifugation of samples affects the levels of serum potassium. Twenty participants donated normal venous blood that was collected in four serum separator tubes per donor, each of which was analyzed at 0, 1, 2, or 4 hr on the Siemens Advia 1800 autoanalyzer. Coefficients of variation (CVs) for potassium levels ranged from 0% to 7.6% with a mean of 3 ± 2%. ANOVA testing of the means for all 20 samples showed a P-value of 0.72 (>0.05) indicating that there was no statistically significant difference between the means of the samples at the four time points. Sixteen samples were found to have CVs that were ≤5%. Two samples showed increases of potassium from the reference range to levels higher than the upper reference limit, one of which had a 4-hr value that was within the reference or normal range (3.5-5 mEq/l). Overall, most samples were found to have reproducible levels of serum potassium. Serum potassium levels from stored whole blood collected in serum separator tubes are, for the most part, stable at room temperature for at least 4 hr prior to analysis. However, some samples can exhibit significant fluctuations of values. © 2015 Wiley Periodicals, Inc.

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

DEFF Research Database (Denmark)

Hjæresen, Marie-Louise; Hageman, Ida; Wörtwein, Gitta

2008-01-01

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

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion.

Science.gov (United States)

Thurlow, John S; Little, Dustin J; Baker, Thomas P; Yuan, Christina M

2013-06-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion.

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion*

Science.gov (United States)

Thurlow, John S.; Little, Dustin J.; Baker, Thomas P.; Yuan, Christina M.

2013-01-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion. PMID:26064493

A Novel Reconfigurable Logic Unit Based on the DNA-Templated Potassium-Concentration-Dependent Supramolecular Assembly.

Science.gov (United States)

Yang, Chunrong; Zou, Dan; Chen, Jianchi; Zhang, Linyan; Miao, Jiarong; Huang, Dan; Du, Yuanyuan; Yang, Shu; Yang, Qianfan; Tang, Yalin

2018-03-15

Plenty of molecular circuits with specific functions have been developed; however, logic units with reconfigurability, which could simplify the circuits and speed up the information process, are rarely reported. In this work, we designed a novel reconfigurable logic unit based on a DNA-templated, potassium-concentration-dependent, supramolecular assembly, which could respond to the input stimuli of H + and K + . By inputting different concentrations of K + , the logic unit could implement three significant functions, including a half adder, a half subtractor, and a 2-to-4 decoder. Considering its reconfigurable ability and good performance, the novel prototypes developed here may serve as a promising proof of principle in molecular computers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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....

Altered potassium homeostasis in Crohn's disease

International Nuclear Information System (INIS)

Schober, O.; Hundeshagen, H.; Bosaller, C.; Lehr, L.

1983-01-01

The total body potassium (TBK), serum potassium, and the number of red blood cell ouabain-binding sites was studied in 94 patients with Crohn's diease. TBK was measured by counting the endogenous 40 K in a whole body counter. TBK was 87%+-13% in 94 patients was Crohn's disease, while in control subjects, it was 97%+-12% (n=24). This significant reduction in TBK was accompanied by normal serum potassium levels (4.4+-0.5 mM). TBK was significantly correlated with the Crohn's disease activity index (r=0.79, n=113, P 3 H-ouabain showed a significant increse in the number of Na-K pumps in Crohn's disease (396+-65, n=27) compared with the control group. 290+-45 (n=24). These results support the suggestion that changes in TBK may regulate the synthesis of Na-K pump molecules. The total body potassium depletion and the need for a preoperative nutritional support in Crohn's disease are discussed. (orig.)

VEGF attenuated increase of outward delayed-rectifier potassium currents in hippocampal neurons induced by focal ischemia via PI3-K pathway.

Science.gov (United States)

Wu, K W; Yang, P; Li, S S; Liu, C W; Sun, F Y

2015-07-09

We recently indicated that the vascular endothelial growth factor (VEGF) protects neurons against hypoxic death via enhancement of tyrosine phosphorylation of Kv1.2, an isoform of the delayed-rectifier potassium channels through activation of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway. The present study investigated whether VEGF could attenuate ischemia-induced increase of the potassium currents in the hippocampal pyramidal neurons of rats after ischemic injury. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) to induce brain ischemia. The whole-cell patch-clamp technique was used to record the potassium currents of hippocampal neurons in brain slices from the ischemically injured brains of the rats 24h after MCAO. We detected that transient MCAO caused a significant increase of voltage-gated potassium currents (Kv) and outward delayed-rectifier potassium currents (IK), but not outward transient potassium currents (IA), in the ipsilateral hippocampus compared with the sham. Moreover, we found that VEGF could acutely, reversibly and voltage-dependently inhibit the ischemia-induced IK increase. This inhibitory effect of VEGF could be completely abolished by wortmannin, an inhibitor of PI3-K. Our data indicate that VEGF attenuates the ischemia-induced increase of IK via activation of the PI3-K signaling pathway. Published by Elsevier Ltd.

Effect of potassium channel modulators in mouse forced swimming test

Science.gov (United States)

Galeotti, Nicoletta; Ghelardini, Carla; Caldari, Bernardetta; Bartolini, Alessandro

1999-01-01

The effect of intracerebroventricular (i.c.v.) administration of different potassium channel blockers (tetraethylammonium, apamin, charybdotoxin, gliquidone), potassium channel openers (pinacidil, minoxidil, cromakalim) and aODN to mKv1.1 on immobility time was evaluated in the mouse forced swimming test, an animal model of depression. Tetraethylammonium (TEA; 5 μg per mouse i.c.v.), apamin (3 ng per mouse i.c.v.), charybdotoxin (1 μg per mouse i.c.v.) and gliquidone (6 μg per mouse i.c.v.) administered 20 min before the test produced anti-immobility comparable to that induced by the tricyclic antidepressants amitriptyline (15 mg kg−1 s.c.) and imipramine (30 mg kg−1 s.c.). By contrast pinacidil (10–20 μg per mouse i.c.v.), minoxidil (10–20 μg per mouse i.c.v.) and cromakalim (20–30 μg per mouse i.c.v.) increased immobility time when administered in the same experimental conditions. Repeated administration of an antisense oligonucleotide (aODN) to the mKv1.1 gene (1 and 3 nmol per single i.c.v. injection) produced a dose-dependent increase in immobility time of mice 72 h after the last injection. At day 7, the increasing effect produced by aODN disappeared. A degenerate mKv1.1 oligonucleotide (dODN), used as control, did not produce any effect in comparison with saline- and vector-treated mice. At the highest effective dose, potassium channels modulators and the mKv1.1 aODN did not impair motor coordination, as revealed by the rota rod test, nor did they modify spontaneous motility as revealed by the Animex apparatus. These results suggest that modulation of potassium channels plays an important role in the regulation of immobility time in the mouse forced swimming test. PMID:10323599

Local time and cutoff rigidity dependences of storm time increase associated with geomagnetic storms

International Nuclear Information System (INIS)

Kudo, S.; Wada, M.; Tanskanen, P.; Kodama, M.

1987-01-01

The cosmic ray increases due to considerable depressions of cosmic ray cutoff rigidity during large geomagnetic storms are investigated. Data from a worldwide network of cosmic ray neutron monitors are analyzed for 17 geomagnetic storms which occurred in the quiet phase of the solar activity cycle during 1966-1978. As expected from the longitudinal asymmetry of the low-altitude geomagnetic field during large geomagnetic storms, a significant local time dependence of the increment in the cosmic ray during large geomagnetic storms, a significant local time dependence of the increment in the cosmic ray intensity is obtained. It is shown that the maximum phases of the local time dependence occur at around 1800 LT and that the amplitudes of the local time dependence are consistent with presently available theoretical estimates. The dependence of the increment on the cutoff rigidity is obtained for both the local time dependent part and the local time independent part of the storm time increase. The local time independent part, excluding the randomizing local time dependent part, shows a clear-cut dependence on cutoff rigidity which is consistent with theoretical estimates

Adaptation of Bacillus subtilis to Life at Extreme Potassium Limitation.

Science.gov (United States)

Gundlach, Jan; Herzberg, Christina; Hertel, Dietrich; Thürmer, Andrea; Daniel, Rolf; Link, Hannes; Stülke, Jörg

2017-07-05

Potassium is the most abundant metal ion in every living cell. This ion is essential due to its requirement for the activity of the ribosome and many enzymes but also because of its role in buffering the negative charge of nucleic acids. As the external concentrations of potassium are usually low, efficient uptake and intracellular enrichment of the ion is necessary. The Gram-positive bacterium Bacillus subtilis possesses three transporters for potassium, KtrAB, KtrCD, and the recently discovered KimA. In the absence of the high-affinity transporters KtrAB and KimA, the bacteria were unable to grow at low potassium concentrations. However, we observed the appearance of suppressor mutants that were able to overcome the potassium limitation. All these suppressor mutations affected amino acid metabolism, particularly arginine biosynthesis. In the mutants, the intracellular levels of ornithine, citrulline, and arginine were strongly increased, suggesting that these amino acids can partially substitute for potassium. This was confirmed by the observation that the supplementation with positively charged amino acids allows growth of B. subtilis even at the extreme potassium limitation that the bacteria experience if no potassium is added to the medium. In addition, a second class of suppressor mutations allowed growth at extreme potassium limitation. These mutations result in increased expression of KtrAB, the potassium transporter with the highest affinity and therefore allow the acquisition and accumulation of the smallest amounts of potassium ions from the environment. IMPORTANCE Potassium is essential for every living cell as it is required for the activity for many enzymes and for maintaining the intracellular pH by buffering the negative charge of the nucleic acids. We have studied the adaptation of the soil bacterium Bacillus subtilis to life at low potassium concentrations. If the major high-affinity transporters are missing, the bacteria are unable to grow

Time-dependent effects of ultraviolet and nonthermal atmospheric pressure plasma on the biological activity of titanium

Science.gov (United States)

Choi, Sung-Hwan; Jeong, Won-Seok; Cha, Jung-Yul; Lee, Jae-Hoon; Yu, Hyung-Seog; Choi, Eun-Ha; Kim, Kwang-Mahn; Hwang, Chung-Ju

2016-09-01

Here, we evaluated time-dependent changes in the effects of ultraviolet (UV) and nonthermal atmospheric pressure plasma (NTAPPJ) on the biological activity of titanium compared with that of untreated titanium. Grade IV machined surface titanium discs (12-mm diameter) were used immediately and stored up to 28 days after 15-min UV or 10-min NTAPPJ treatment. Changes of surface characteristics over time were evaluated using scanning electron microscopy, surface profiling, contact angle analysis, X-ray photoelectron spectroscopy, and surface zeta-potential. Changes in biological activity over time were as determined by analysing bovine serum albumin adsorption, MC3T3-E1 early adhesion and morphometry, and alkaline phosphatase (ALP) activity between groups. We found no differences in the effects of treatment on titanium between UV or NTAPPJ over time; both treatments resulted in changes from negatively charged hydrophobic (bioinert) to positively charged hydrophilic (bioactive) surfaces, allowing enhancement of albumin adsorption, osteoblastic cell attachment, and cytoskeleton development. Although this effect may not be prolonged for promotion of cell adhesion until 4 weeks, the effects were sufficient to maintain ALP activity after 7 days of incubation. This positive effect of UV and NTAPPJ treatment can enhance the biological activity of titanium over time.

Enhanced K+-channel-mediated endothelium-dependent local and conducted dilation of small mesenteric arteries from ApoE−/− mice

Science.gov (United States)

Beleznai, Timea; Takano, Hiromichi; Hamill, Claire; Yarova, Polina; Douglas, Gillian; Channon, Keith; Dora, Kim

2011-01-01

Aims Agonists that evoke smooth muscle cell hyperpolarization have the potential to stimulate both local and conducted dilation. We investigated whether the endothelium-dependent vasodilators acetylcholine (ACh) and SLIGRL stimulated conducted dilation and whether this was altered by deficiency in apolipoprotein E (ApoE−/−). Methods and results Isolated mesenteric arteries were cannulated, pressurized, and precontracted with phenylephrine. Agonists were either added to the bath to study local dilation or were restricted to one end of arteries to study conducted dilation. An enhanced sensitivity to both ACh and SLIGRL was observed in mesenteric arteries from ApoE−/− mice compared with wild-type controls. Inhibition of nitric oxide (NO) synthase blocked ACh responses, but had no effect on maximum dilation to SLIGRL. SLIGRL increased endothelial cell Ca2+, hyperpolarized smooth muscle cells, and fully dilated arteries. The NO-independent dilation to SLIGRL was blocked with high [KCl] or Ca2+-activated K+-channel blockers. The hyperpolarization and dilation to SLIGRL passed through the artery to at least 2.5 mm upstream. The conducted dilation was not affected by a deficit in ApoE and could also be stimulated by ACh, suggesting NO itself could stimulate conducted dilation. Conclusion In small mesenteric arteries of ApoE−/− mice, NO-independent dilation is enhanced. Since both NO-dependent and -independent pathways can stimulate local and conducted dilation, the potential for reducing vascular resistance is improved in these vessels. PMID:21690174

16-Channel surface coil for 13C-hyperpolarized spectroscopic imaging of cardiac metabolism in pig heart

DEFF Research Database (Denmark)

Frijia, Francesca; Santarelli, Maria Filomena; Koellisch, Ulrich

2016-01-01

Magnetic resonance spectroscopy (MRS) of hyperpolarized 13C pyruvate and its metabolites in large animal models is a powerful tool for assessing cardiac metabolism in patho-physiological conditions. In 13C studies, a high signal-to-noise ratio (SNR) is crucial to overcome the intrinsic data quality...... both targets. In this study, a 16-channel receive surface coil was designed for 13C hyperpolarized studies of the pig heart with a clinical 3-T scanner. The coil performance was characterized by phantom experiments and compared with that of a birdcage coil used in transmit/receive mode. Segmental...... of the 16-channel coil is recommended for studies of septal and anterior LV walls....

Effects of allocryptopine on outward potassium current and slow delayed rectifier potassium current in rabbit myocardium.

Science.gov (United States)

Fu, Yi-Cheng; Zhang, Yu; Tian, Liu-Yang; Li, Nan; Chen, Xi; Cai, Zhong-Qi; Zhu, Chao; Li, Yang

2016-05-01

Allocryptopine (ALL) is an effective alkaloid of Corydalis decumbens (Thunb.) Pers. Papaveraceae and has proved to be anti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current (I to) and slow delayed rectifier potassium current (I Ks). The monophasic action potential (MAP) technique was used to record the MAP duration of the epicardium (Epi), myocardium (M) and endocardium (Endo) of the rabbit heart and the whole cell patch clamp was used to record I to and I Ks in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization (TDR) in rabbit transmural ventricular wall. ALL decreased the current densities of I to and I Ks in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation of I to in M layers and partly inhibit the channel openings of I to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of I Ks channel in Epi and Endo layers without affecting its activation. Our study gives partially explanation about the mechanisms of transmural inhibition of I to and I Ks channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings.

The Calcium-Activated Slow AHP: Cutting Through the Gordian Knot

Directory of Open Access Journals (Sweden)

Rodrigo eAndrade

2012-10-01

Full Text Available The phenomenon known as the slow afterhyperpolarization (sAHP was originally described more than 30 years ago in pyramidal cells as a slow, Ca2+-dependent afterpotential controlling spike frequency adaptation. Subsequent work showed that similar sAHPs were widely expressed in the brain and were mediated by a Ca2+-activated potassium current that was voltage independent, insensitive to most potassium channel blockers, and strongly modulated by neurotransmitters. However the molecular basis for this current has remained poorly understood. The sAHP was initially imagined to reflect the activation of a potassium channel directly gated by Ca2+ but recent studies have begun to question this idea. The sAHP is distinct from the Ca2+-dependent fast and medium AHPs in that it appears to sense cytoplasmic [Ca2+]i and recent evidence implicates proteins of the neuronal calcium sensor family as diffusible cytoplasmic Ca2+ sensors for the sAHP. Translocation of Ca2+-bound sensor to the plasma membrane would then be an intermediate step between Ca2+ and the sAHP channels. Parallel studies strongly suggest that the sAHP current is carried by different potassium channel types depending on the cell type. Finally, the sAHP current is dependent on membrane PtdIns(4,5P2 and Ca2+ appears to gate this current by increasing PtdIns(4,5P2 levels. Because membrane PtdIns(4,5P2 is essential for the activity of many potassium channels, these finding have led us to hypothesize that the sAHP reflects a transient Ca2+-induced increase in the local availability of PtdIns(4,5P2 which then activates a variety of potassium channels. If this view is correct, the sAHP current would not represent a unitary ionic current but the embodiment of a generalized potassium channel gating mechanism. This model can potentially explain the cardinal features of the sAHP, including its cellular heterogeneity, slow kinetics, dependence on cytoplasmic [Ca2+], high temperature-dependence, and

(Vapour + liquid) equilibria, volumetric and compressibility behaviour of binary and ternary aqueous solutions of 1-hexyl-3-methylimidazolium chloride, methyl potassium malonate, and ethyl potassium malonate

International Nuclear Information System (INIS)

Sadeghi, Rahmat; Mahdavi, Adibeh

2012-01-01

Highlights: ► VLE and volumetry of binary and ternary [C 6 mim][Cl], MPM and EPM aqueous solutions. ► Constant a w lines show small negative deviation from the linear isopiestic relation. ► Solute–water interactions follow the order: EPM > MPM > [C 6 mim][Cl]. ► MPM and EPM have a very weak salting-out effect on [C 6 mim][Cl] aqueous solutions. - Abstract: (Vapour + liquid) equilibrium data (water activity, vapour pressure, osmotic coefficient, and activity coefficient) of binary aqueous solutions of 1-hexyl-3-methylimidazolium chloride ([C 6 mim][Cl]), methyl potassium malonate, and ethyl potassium malonate and ternary {[C 6 mim][Cl] + methyl potassium malonate} and {[C 6 mim][Cl] + ethyl potassium malonate} aqueous solutions were obtained through the isopiestic method at T = 298.15 K. These results reveal that the ionic liquid behaves as surfactant-like and aggregates in aqueous solutions at molality about 0.4 mol · kg −1 . The constant water activity lines of all the ternary systems investigated show small negative deviations from the linear isopiestic relation (Zdanovskii–Stokes–Robinson rule) derived using the semi-ideal hydration model. The density and speed of sound measurements were carried out on solutions of methyl potassium malonate and ethyl potassium malonate in water and of [C 6 mim][Cl] in aqueous solutions of 0.25 mol · kg −1 methyl potassium malonate and ethyl potassium malonate at T = (288.15 to 308.15) K at atmospheric pressure. From the experimental density and speed of sound data, the values of the apparent molar volume, apparent molar isentropic compressibility and excess molar volume were evaluated and from which the infinite dilution apparent molar volume and infinite dilution apparent molar isentropic compressibility were calculated at each temperature. Although, there are no clear differences between the values of the apparent molar volume of [C 6 mim][Cl] in pure water and in methyl potassium malonate or ethyl

MO-DE-206-03: Quantifying Metabolism with Hyperpolarized MR

Energy Technology Data Exchange (ETDEWEB)

Bankson, J. [The University of Texas M.D. Anderson Cancer Center (United States)

2016-06-15

In this symposium jointly sponsored by the World Molecular Imaging Society (WMIS) and the AAPM, luminary speakers on imaging metabolism will discuss three impactful topics. The first presentation on Cellular Metabolism of FDG will be given by Guillem Pratx (Stanford). This presentation will detail new work on looking at how the most common molecular imaging agent, fluoro-deoxy-glucose is metabolized at a cellular level. This will be followed by a talk on an improved approach to whole-body PET imaging by Simon Cherry (UC Davis). Simon’s work on a new whole-body PET imaging system promises to have dramatic improvement in our ability to detect and characterize cancer using PET. Finally, Jim Bankson (MD Anderson) will discuss extremely sophisticated approaches to quantifying hyperpolarized-13-C pyruvate metabolism using MR imaging. This technology promises to compliment the exquisite sensitivity of PET with an ability to measure not just uptake, but tumor metabolism. Learning Objectives: Understand the metabolism of FDG at a cellular level. Appreciate the engineering related to a novel new high-sensitivity whole-body PET imaging system. Understand the process of hyperpolarization, how pyruvate relates to metabolism and how advanced modeling can be used to better quantify this data. G. Pratx, Funding: 5R01CA186275, 1R21CA193001, and Damon Runyon Cancer Foundation. S. Cherry, National Institutes of Health; University of California, Davis; Siemens Medical SolutionsJ. Bankson, GE Healthcare; NCI P30-CA016672; CPRIT PR140021-P5.

Fruit-body production and 137Cs-activity of Cantharellus cibarius after nitrogen and potassium fertilization

International Nuclear Information System (INIS)

Nohrstedt, H.Oe.

1994-01-01

A study of the possible effect of fertilization with nitrogen and potassium on fruit-body production and 137 Cs-activity concentration of Cantharellus cibarius was carried out in a pine forest in the eastern part of central Sweden. Nitrogen, in the form of ammonium nitrate, was added twice, in 1984 and 1990, at a dose of 150 kg N ha -1 . Fruit-body production was measured during 1985-1991, and the 137 Cs-activity concentration during 1988-1991. Fruit-body production showed a pronounced variation between years. The ratio between the highest annual production and the lowest was about 20. No statistically significant effects of either the fertilization treatments on production were observed. However, nitrogen fertilization showed a tendency towards a decrease in production by about 30%. The field site is situated in an area substantially affected by the fallout from the Chernobyl accident in 1986. The fruit-bodies on the site had a clearly elevated activity concentration of 137 Cs, which averaged 15 Bq q -1 d.m. for all plots and years. On the 4.5 ha study site, the 137 Cs-activity concentration varied by a factor of 10 between individual plots. The year with the highest fruit-body production had the lowest 137 Cs-activity concentration. The fertilizations lacked statistically significant effect in 137 Cs-activity concentration, but a 50% reduction was indicated for potassium fertilization causing the concentration to fall below the Swedish health limit for human food. 31 refs, 3 figs

Influence of thermal treatment on OSL regeneration in potassium chloride

International Nuclear Information System (INIS)

Majgier, Renata; Biernacka, Magdalena; Mandowski, Arkadiusz

2016-01-01

Optically stimulated luminescence (OSL) of pure analytical potassium chloride (KCl) prepared in two different forms (crystals and pellets) was studied. The occurrence of regeneration effect (self-renewal of the OSL signal) in the material was examined. The experiments using the variable delay OSL (VD-OSL) method were carried out. Performed measurements allowed to determine time scale of the phenomenon, as well as quantitative changes of regeneration depending on thermal treatment before and after irradiation. Significant increase of the OSL regeneration was noticeable for pellets after the application of the annealing before irradiation, while for crystals a substantial decrease of regeneration was observed. Preheating applied after irradiation caused that self-renewal of OSL signal was drastically reduced or completely suppressed depending on the form of KCl samples. - Highlights: • Optically stimulated luminescence (OSL) of potassium chloride (KCl) was studied. • The measurements were performed using the variable delay OSL method (VD-OSL). • It was found that regeneration of OSL intensity in KCl could be as high as 2000%. • Annealing caused reduction of OSL renewal for crystals and its increase for pellets. • Preheating after irradiation removed or significantly reduced the OSL regeneration.

Time-resolved monitoring of enzyme activity with ultrafast Hyper-CEST spectroscopy.

Science.gov (United States)

Döpfert, Jörg; Schnurr, Matthias; Kunth, Martin; Rose, Honor May; Hennig, Andreas; Schröder, Leif

2017-12-23

We propose a method to dynamically monitor the progress of an enzymatic reaction using NMR of hyperpolarized 129 Xe in a host-guest system. It is based on a displacement assay originally designed for fluorescence experiments that exploits the competitive binding of the enzymatic product on the one hand and a reporter dye on the other hand to a supramolecular host. Recently, this assay has been successfully transferred to NMR, using xenon as a reporter, cucurbit[6]uril as supramolecular host, and chemical exchange saturation transfer with hyperpolarized Xe (Hyper-CEST) as detection technique. Its advantage is that the enzyme acts on the unmodified substrate and that only the product is detected through immediate inclusion into the host. We here apply a method that drastically accelerates the acquisition of Hyper-CEST spectra in vitro using magnetic field gradients. This allows monitoring the dynamic progress of the conversion of lysine to cadaverine with a temporal resolution of ~30 s. Moreover, the method only requires to sample the very early onset of the reaction (Hyper-CEST results correlate with xenon T 2 measurements performed during the enzymatic reaction. This suggests that ultrafast Hyper-CEST spectroscopy can be used for dynamically monitoring enzymatic activity with NMR. Copyright © 2017 John Wiley & Sons, Ltd.

Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized C-13 magnetic resonance

DEFF Research Database (Denmark)

Mishkovsky, Mor; Anderson, Brian; Karlsson, Magnus

2017-01-01

The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, C-13 magnetic resonance spectroscopy (MRS) allows following the fate of C-13-enriched substrates through metabolic pathways. We herein...... glucose is split into 3-carbon intermediates by aldolase. This unique method allows direct detection of glycolysis in vivo in the healthy brain in a noninvasive manner....... demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized C-13 MRS. In particular, the dynamic C-13-labeling of pyruvate and lactate formed from C-13-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6-H-2(5), 3...

Potassium toxicity at low serum potassium levels with refeeding syndrome.

Science.gov (United States)

Vemula, Praveen; Abela, Oliver G; Narisetty, Keerthy; Rhine, David; Abela, George S

2015-01-01

Refeeding syndrome is a life-threatening condition occurring in severely malnourished patients after initiating feeding. Severe hypophosphatemia with reduced adenosine triphosphate production has been implicated, but little data are available regarding electrolyte abnormalities. In this case, we report electrocardiographic changes consistent with hyperkalemia during potassium replacement after a serum level increase from 1.9 to 2.9 mEq/L. This was reversed by lowering serum potassium back to 2.0 mEq/L. In conclusion, the patient with prolonged malnutrition became adapted to low potassium levels and developed potassium toxicity with replacement. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of calcium-activated potassium channels with small conductance in bradykinin-induced vasodilation of porcine retinal arterioles

DEFF Research Database (Denmark)

Dalsgaard, Thomas; Kroigaard, Christel; Bek, Toke

2009-01-01

PURPOSE: Endothelial dysfunction and impaired vasodilation may be involved in the pathogenesis of retinal vascular diseases. In the present study, the mechanisms underlying bradykinin vasodilation were examined and whether calcium-activated potassium channels of small (SK(Ca)) and intermediate (IK...

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion*

OpenAIRE

Thurlow, John S.; Little, Dustin J.; Baker, Thomas P.; Yuan, Christina M.

2013-01-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ?5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose ...

Brain Imaging Using Hyperpolarized 129Xe Magnetic Resonance Imaging.

Science.gov (United States)

Chahal, Simrun; Prete, Braedan R J; Wade, Alanna; Hane, Francis T; Albert, Mitchell S

2018-01-01

Hyperpolarized (HP) 129 Xe magnetic resonance imaging (MRI) is a novel iteration of traditional MRI that relies on detecting the spins of 1 H. Since 129 Xe is a gaseous signal source, it can be used for lung imaging. Additionally, 129 Xe dissolves in the blood stream and can therefore be detectable in the brain parenchyma and vasculature. In this work, we provide detailed information on the protocols that we have developed to image 129 Xe within the brains of both rodents and human subjects. © 2018 Elsevier Inc. All rights reserved.

The dependence of orange-red IRSL decay curves of potassium feldspars on sample temperature

International Nuclear Information System (INIS)

Fattahi, Morteza

2004-01-01

This paper presents the effects of stimulation temperature on the infrared stimulated orange-red (600-650 nm) luminescence emission (orange-red infrared simulated luminescence (IRSL)) in potassium feldspar. Investigations explore the relationship between initial (0-2 s), integral (0-100 s), net initial (0-2 s less background over 2 s), net integral (0-100 s less background over 100 s) and last 2 s of the orange-red IRSL signals obtained for 100 s versus stimulation temperature (20-460 degree sign C) on both unpreheated and preheated samples. In the potassium feldspar sample examined, competition effects, including thermal enhancement, depletion and possibly quenching affect the orange-red IRSL signals measured. Observed effects (e.g., thermal enhancement, thermal activation energy and the decay rate) over the temperature range 20-120 degree sign C may be explained by tunnelling luminescence processes, IR transitions to the conduction band following excitations from ground state of electron trap by acquiring thermal energy from the lattice and or the random-walk band-tail model. Preheating prior to orange-red IRSL and Thermoluminescence (TL) measurements provides evidence that there are both shallow and deep traps responsible for low- and high-temperature orange-red IRSL and TL peaks. The effects of both preheating and IR bleaching on the orange-red thermally stimulated luminescence (red emission during thermoluminescence, RTL) provide evidence that bleached RTL traps have no significant contribution in the production of orange-red IRSL signals

Aldosterone downregulates delayed rectifier potassium currents through an angiotensin type 1 receptor-dependent mechanism.

Science.gov (United States)

Lv, Yankun; Wang, Yanjun; Zhu, Xiaoran; Zhang, Hua

2018-01-01

We have previously shown that aldosterone downregulates delayed rectifier potassium currents (I Ks ) via activation of the mineralocorticoid receptor (MR) in adult guinea pig cardiomyocytes. Here, we investigate whether angiotensin II/angiotensin type 1 receptor (AngII/AT1R) and intracellular calcium also play a role in these effects. Ventricular cardiomyocytes were isolated from adult guinea pigs and incubated with aldosterone (1 μmol·L -1 ) either alone or in combination with enalapril (1 μmol·L -1 ), losartan (1 μmol·L -1 ), nimodipine (1 μmol·L -1 ), or BAPTA-AM (2.5 μmol·L -1 ) for 24 h. We used the conventional whole cell patch-clamp technique to record the I Ks component. In addition, we evaluated expression of the I Ks subunits KCNQ1 and KCNE1 using Western blotting. Our results showed that both enalapril and losartan, but not nimodipine or BAPTA-AM, completely reversed the aldosterone-induced inhibition of I Ks and its effects on KCNQ1/KCNE1 protein levels. Furthermore, we found that AngII/AT1R mediates the inhibitory effects of aldosterone on I Ks . Finally, the downregulation of I Ks induced by aldosterone did not occur secondarily to a change in intracellular calcium concentrations. Taken together, our findings demonstrate that crosstalk between MR and AT1R underlies the effects of aldosterone, and provide new insights into the mechanism underlying potassium channels.

Computational study on potassium picrate crystal

Energy Technology Data Exchange (ETDEWEB)

Ju, Xue-Hai; Lu, Ya-Lin; Ma, Xiu-Fang; Xiao, He-Ming [Department of Chemistry, Nanjing University of Science and Technology, Nanjing, 210094 (China)

2006-08-15

DFT calculation at the B3LYP level was performed on crystalline potassium picrate. The frontier bands are slightly fluctuant. The energy gap between the highest occupied crystal orbital (HOCO) and the lowest unoccupied crystal orbital (LUCO) is 0.121 a.u. (3.29 eV). The carbon atoms that are connected with the nitro groups make up the narrow lower energy bands, with small contributions from nitro oxygen and phenol oxygen. The higher energy bands consist of orbitals from the nitro groups and carbon atom. The potassium bears almost 1 a.u. positive charge. The potassium forms ionic bonding with the phenol oxygen and the nitro oxygen at the same time. The crystal lattice energy is predicted to be -574.40 kJ/mol at the B3LYP level determined with the effective core pseudopotential HAYWSC-31G basis set for potassium and 6-31G** basis set for other atoms. (Abstract Copyright [2006], Wiley Periodicals, Inc.)

Adsorption of pharmaceuticals to microporous activated carbon treated with potassium hydroxide, carbon dioxide, and steam.

Science.gov (United States)

Fu, Heyun; Yang, Liuyan; Wan, Yuqiu; Xu, Zhaoyi; Zhu, Dongqiang

2011-01-01

Adsorption of sulfapyridine, tetracycline, and tylosin to a commercial microporous activated carbon (AC) and its potassium hydroxide (KOH)-, CO-, and steam-treated counterparts (prepared by heating at 850°C) was studied to explore efficient adsorbents for the removal of selected pharmaceuticals from water. Phenol and nitrobenzene were included as additional adsorbates, and nonporous graphite was included as a model adsorbent. The activation treatments markedly increased the specific surface area and enlarged the pore sizes of the mesopores of AC (with the strongest effects shown on the KOH-treated AC). Adsorption of large-size tetracycline and tylosin was greatly enhanced, especially for the KOH-treated AC (more than one order of magnitude), probably due to the alleviated size-exclusion effect. However, the treatments had little effect on adsorption of low-size phenol and nitrobenzene due to the predominance of micropore-filling effect in adsorption and the nearly unaffected content of small micropores causative to such effect. These hypothesized mechanisms on pore-size dependent adsorption were further tested by comparing surface area-normalized adsorption data and adsorbent pore size distributions with and without the presence of adsorbed antibiotics. The findings indicate that efficient adsorption of bulky pharmaceuticals to AC can be achieved by enlarging the adsorbent pore size through suitable activation treatments. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

‘Sleepy’ inward rectifier channels in guinea-pig cardiomyocytes are activated only during strong hyperpolarization

Science.gov (United States)

Liu, Gong Xin; Daut, Jürgen

2002-01-01

K+ channels of isolated guinea-pig cardiomyocytes were studied using the patch-clamp technique. At transmembrane potentials between −120 and −220 mV we observed inward currents through an apparently novel channel. The novel channel was strongly rectifying, no outward currents could be recorded. Between −200 and −160 mV it had a slope conductance of 42.8 ± 3.0 pS (s.d.; n = 96). The open probability (Po) showed a sigmoid voltage dependence and reached a maximum of 0.93 at −200 mV, half-maximal activation was approximately −150 mV. The voltage dependence of Po was not affected by application of 50 μm isoproterenol. The open-time distribution could be described by a single exponential function, the mean open time ranged between 73.5 ms at −220 mV and 1.4 ms at −160 mV. At least two exponential components were required to fit the closed time distribution. Experiments with different external Na+, K+ and Cl− concentrations suggested that the novel channel is K+ selective. Extracellular Ba2+ ions gave rise to a voltage-dependent reduction in Po by inducing long closed states; Cs+ markedly reduced mean open time at −200 mV. In cell-attached recordings the novel channel frequently converted to a classical inward rectifier channel, and vice versa. This conversion was not voltage dependent. After excision of the patch, the novel channel always converted to a classical inward rectifier channel within 0–3 min. This conversion was not affected by intracellular Mg2+, phosphatidylinositol (4,5)-bisphosphate or spermine. Taken together, our findings suggest that the novel K+ channel represents a different ‘mode’ of the classical inward rectifier channel in which opening occurs only at very negative potentials. PMID:11897847

Regulation of ATP-sensitive K+ channels in insulinoma cells: Activation by somatostatin and protein kinase C and the role of cAMP

International Nuclear Information System (INIS)

De Weille, J.R.; Schmid-Antomarchi, H.; Fosset, M.; Lazdunski, M.

1989-01-01

The actions of somatostatin and of the phorbol ester 4β-phorbol 12-myristate 13-acetate (PMA) were studied in rat insulinoma (RINm5F) cells by electrophysiological and 86 Rb + flux techniques. Both PMA and somatostatin hyperpolarize insulinoma cells by activating ATP-sensitive K + channels. The presence of intracellular GTP is required for the somatostatin effects. PMA- and somatostatin-induced hyperpolarization and channel activity are inhibited by the sulfonylurea glibenclamide. Glibenclamide-sensitive 86 Rb + efflux from insulinoma cells is stimulated by somatostatin in a dose-dependent manner (half maximal effect at 0.7 nM) and abolished by pertussis toxin pretreatment. Mutual roles of a GTP-binding protein, of protein kinase C, and of cAMP in the regulation of ATP-sensitive K + channels are discussed

Interplay of activation kinetics and the derivative conductance determines resonance properties of neurons

Science.gov (United States)

Pena, Rodrigo F. O.; Ceballos, Cesar C.; Lima, Vinicius; Roque, Antonio C.

2018-04-01

In a neuron with hyperpolarization activated current (Ih), the correct input frequency leads to an enhancement of the output response. This behavior is known as resonance and is well described by the neuronal impedance. In a simple neuron model we derive equations for the neuron's resonance and we link its frequency and existence with the biophysical properties of Ih. For a small voltage change, the component of the ratio of current change to voltage change (d I /d V ) due to the voltage-dependent conductance change (d g /d V ) is known as derivative conductance (GhDer). We show that both GhDer and the current activation kinetics (characterized by the activation time constant τh) are mainly responsible for controlling the frequency and existence of resonance. The increment of both factors (GhDer and τh) greatly contributes to the appearance of resonance. We also demonstrate that resonance is voltage dependent due to the voltage dependence of GhDer. Our results have important implications and can be used to predict and explain resonance properties of neurons with the Ih current.

How the signal‐to‐noise ratio influences hyperpolarized 13C dynamic MRS data fitting and parameter estimation

DEFF Research Database (Denmark)

Santarelli, Maria Filomena; Positano, Vincenzo; Giovannetti, Giulio

2012-01-01

signals with low signal‐to‐noise ratio (SNR). The relationship between SNR and the precision of quantitative analysis for the evaluation of the in vivo kinetic behavior of metabolites is unknown. In this article, this topic is addressed by Monte Carlo simulations, covering the problem of MRS signal model......MRS of hyperpolarized 13C‐labeled compounds represents a promising technique for in vivo metabolic studies. However, robust quantification and metabolic modeling are still important areas of investigation. In particular, time and spatial resolution constraints may lead to the analysis of MRS...

Determination of potassium concentration in salt water for residual beta radioactivity measurements

International Nuclear Information System (INIS)

Suarez-Navarro, J.A.; Pujol, Ll.

2004-01-01

High interferences may arise in the determination of potassium concentration in salt water. Several analytical methods were studied to determine which method provided the most accurate measurements of potassium concentration. This study is relevant for radiation protection because the exact amount of potassium in water samples must be known for determinations of residual beta activity concentration. The fitting algorithm of the calibration curve and estimation of uncertainty in potassium determinations were also studied. The reproducibility of the proposed analytical method was tested by internal and external validation. Furthermore, the residual beta activity concentration of several Spanish seawater and brackish river water samples was determined using the proposed method

Hyperpolarized [1-(13) C]pyruvate MRI for noninvasive examination of placental metabolism and nutrient transport: A feasibility study in pregnant guinea pigs.

Science.gov (United States)

Friesen-Waldner, Lanette J; Sinclair, Kevin J; Wade, Trevor P; Michael, Banoub; Chen, Albert P; de Vrijer, Barbra; Regnault, Timothy R H; McKenzie, Charles A

2016-03-01

To test the feasibility of hyperpolarized [1-(13) C]pyruvate magnetic resonance imaging (MRI) for noninvasive examination of guinea pig fetoplacental metabolism and nutrient transport. Seven pregnant guinea pigs with a total of 30 placentae and fetuses were anesthetized and scanned at 3T. T1 -weighted (1) H images were obtained from the maternal abdomen. An 80 mM solution of hyperpolarized [1-(13) C]pyruvate (hereafter referred to as pyruvate) was injected into a vein in the maternal foot. Time-resolved 3D (13) C images were acquired starting 10 seconds after the beginning of bolus injection and every 10 seconds after to 50 seconds. The pregnant guinea pigs were recovered after imaging. Regions of interest (ROIs) were drawn around the maternal heart and each placenta and fetal liver in all slices in the (1) H images. These ROIs were copied to the (13) C images and were used to calculate the sum of the pyruvate and lactate signal intensities for each organ. The signal intensities were normalized by the volume of the organ and the maximum signal in the maternal heart. No adverse events were observed in the pregnant guinea pigs and natural pupping occurred at term (∼68 days). Pyruvate signal was observed in all 30 placentae, and lactate, a by-product of pyruvate metabolism, was also observed in all placentae. The maximum pyruvate and lactate signals in placentae occurred at 20 seconds. In addition to the observation of pyruvate and lactate signals in the placentae, both pyruvate and lactate signals were observed in all fetal livers. The maximum pyruvate and lactate signals in the fetal livers occurred at 10 seconds and 20 seconds, respectively. This work demonstrates the feasibility of using hyperpolarized [1-(13) C]pyruvate MRI to noninvasively examine fetoplacental metabolism and transport of pyruvate in guinea pigs. Hyperpolarized (13) C MRI may provide a novel method for longitudinal studies of fetoplacental abnormalities. © 2015 Wiley Periodicals, Inc.

Sodium pump activity and calcium relaxation in vascular smooth muscle of deoxycorticosterone acetate-salt rats

International Nuclear Information System (INIS)

Soltis, E.E.; Field, F.P.

1986-01-01

The Na + -K + pump activity was determined in femoral arterial smooth muscle from deoxycorticosterone acetate (DOCA)-salt hypertensive rats using potassium relaxation and ouabain-sensitive 86 Rb uptake as indices. The membrane-stabilizing effect of calcium and its relation to Na + -K + pump activity also were examined. Femoral arteries from DOCA-salt rats exhibited a greater relaxation in response to potassium addition after contraction with norepinephrine in a low potassium (0.6 mM) Krebs solution. The concentration of potassium required to produce a 50% relaxation was significantly less in DOCA-salt rats. Ouabain-sensitive 86 Rb uptake was significantly greater at 3, 10, and 20 minutes of 86 Rb incubation in femoral arteries from DOCA-salt rats. Linear regression analysis revealed a significant correlation between the uptake of 86 Rb and time of incubation in both control and DOCA-salt rats. A significant difference in the slopes of the regression lines showed that the rate of uptake was greater in DOCA-salt rats. No difference was observed in ouabain-insensitive 86 Rb uptake. A dose-dependent relaxation in response to increasing concentrations of calcium following contraction to norepinephrine was observed in femoral arteries from control and DOCA-salt rats. The relaxation was directly dependent on the level of extracellular potassium and was blocked by ouabain. Femoral arteries from DOCA-salt rats relaxed to a significantly greater extent in response to calcium at each level of potassium when compared with controls. These results provide further evidence for an increase in Na + -K + pump activity in vascular smooth muscle from DOCA-salt hypertensive rats

Effects of pyruvate dose on in vivo metabolism and quantification of hyperpolarized 13C spectra

DEFF Research Database (Denmark)

Janich, M. A.; Menzel, M. I.; Wiesinger, F.

2012-01-01

Real‐time in vivo measurements of metabolites are performed by signal enhancement of [1‐13C]pyruvate using dynamic nuclear polarization, rapid dissolution and intravenous injection, acquisition of free induction decay signals and subsequent quantification of spectra. The commonly injected dose...... uptake and metabolic conversion. The goal of this study was to examine the effects of a [1‐13C]pyruvate bolus on metabolic conversion in vivo. Spectra were quantified by three different methods: frequency‐domain fitting with LCModel, time‐domain fitting with AMARES and simple linear least‐squares fitting...... in the time domain. Since the simple linear least‐squares approach showed bleeding artifacts and LCModel produced noisier time signals. AMARES performed best in the quantification of in vivo hyperpolarized pyruvate spectra. We examined pyruvate doses of 0.1–0.4 mmol/kg (body mass) in male Wistar rats...

Protonated form: the potent form of potassium-competitive acid blockers.

Directory of Open Access Journals (Sweden)

Hua-Jun Luo

Full Text Available Potassium-competitive acid blockers (P-CABs are highly safe and active drugs targeting H+,K+-ATPase to cure acid-related gastric diseases. In this study, we for the first time investigate the interaction mechanism between the protonated form of P-CABs and human H+,K+-ATPase using homology modeling, molecular docking, molecular dynamics and binding free energy calculation methods. The results explain why P-CABs have higher activities with higher pKa values or at lower pH. With positive charge, the protonated forms of P-CABs have more competitive advantage to block potassium ion into luminal channel and to bind with H+,K+-ATPase via electrostatic interactions. The binding affinity of the protonated form is more favorable than that of the neutral P-CABs. In particular, Asp139 should be a very important binding site for the protonated form of P-CABs through hydrogen bonds and electrostatic interactions. These findings could promote the rational design of novel P-CABs.

Protonated form: the potent form of potassium-competitive acid blockers.

Science.gov (United States)

Luo, Hua-Jun; Deng, Wei-Qiao; Zou, Kun

2014-01-01

Potassium-competitive acid blockers (P-CABs) are highly safe and active drugs targeting H+,K+-ATPase to cure acid-related gastric diseases. In this study, we for the first time investigate the interaction mechanism between the protonated form of P-CABs and human H+,K+-ATPase using homology modeling, molecular docking, molecular dynamics and binding free energy calculation methods. The results explain why P-CABs have higher activities with higher pKa values or at lower pH. With positive charge, the protonated forms of P-CABs have more competitive advantage to block potassium ion into luminal channel and to bind with H+,K+-ATPase via electrostatic interactions. The binding affinity of the protonated form is more favorable than that of the neutral P-CABs. In particular, Asp139 should be a very important binding site for the protonated form of P-CABs through hydrogen bonds and electrostatic interactions. These findings could promote the rational design of novel P-CABs.

Characterization and flip angle calibration of 13C surface coils for hyperpolarization studies

DEFF Research Database (Denmark)

Hansen, Rie Beck; Gutte, Henrik; Larsen, Majbrit M E

The aim of the present work is to address the challenge of optimal The aim of the present work is to address the challenge of optimal flflip angle calibration of ip angle calibration of C surface coils in C surface coils in hyperpolarization studies. To this end, we characterize the spatial pro h...

Wave function for time-dependent harmonically confined electrons in a time-dependent electric field.

Science.gov (United States)

Li, Yu-Qi; Pan, Xiao-Yin; Sahni, Viraht

2013-09-21

The many-body wave function of a system of interacting particles confined by a time-dependent harmonic potential and perturbed by a time-dependent spatially homogeneous electric field is derived via the Feynman path-integral method. The wave function is comprised of a phase factor times the solution to the unperturbed time-dependent Schrödinger equation with the latter being translated by a time-dependent value that satisfies the classical driven equation of motion. The wave function reduces to that of the Harmonic Potential Theorem wave function for the case of the time-independent harmonic confining potential.

Handling of potassium

International Nuclear Information System (INIS)

Schwarz, N.; Komurka, M.

1983-03-01

As a result for the Fast Breeder Development extensive experience is available worldwide with respect to Sodium technology. Due to the extension of the research program to topping cycles with Potassium as the working medium, test facilities with Potassium have been designed and operated in the Institute of Reactor Safety. The different chemical properties of Sodium and Potassium give rise in new safety concepts and operating procedures. The handling problems of Potassium are described in the light of theoretical properties and own experiences. Selected literature on main safety and operating problems complete this report. (Author) [de

Solid state green synthesis and catalytic activity of CuO nanorods in thermal decomposition of potassium periodate

Science.gov (United States)

Patel, Vinay Kumar; Bhattacharya, Shantanu

2017-09-01

The present study reports a facile solid state green synthesis process using the leaf extracts of Hibiscus rosa-sinensis to synthesize CuO nanorods with average diameters of 15-20 nm and lengths up to 100 nm. The as-synthesized CuO nanorods were characterized by x-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy and selected area electron diffraction. The formation mechanism of CuO nanorods has been explained by involving the individual role of amide I (amino groups) and carboxylate groups under excess hydroxyl ions released from NaOH. The catalytic activity of CuO nanorods in thermal decomposition of potassium periodate microparticles (µ-KIO4) microparticles was studied by thermo gravimetric analysis measurement. The original size (~100 µm) of commercially procured potassium periodate was reduced to microscale length scale to about one-tenth by PEG200 assisted emulsion process. The CuO nanorods prepared by solid state green route were found to catalyze the thermal decomposition of µ-KIO4 with a reduction of 18 °C in the final thermal decomposition temperature of potassium periodate.

The inhibitory effects of potassium chloride versus potassium silicate application on 137Cs uptake by rice

International Nuclear Information System (INIS)

Fujimura, Shigeto; Yoshioka, Kunio; Ota, Takeshi; Ishikawa, Tetsuya; Sato, Makoto; Satou, Mutsuto

2016-01-01

After the accident at the Fukushima Dai-ichi Nuclear Power Plant owned by the Tokyo Electric Power Company on 11 March 2011, potassium fertilizer was applied to agricultural fields in the southern Tohoku and northern Kanto regions of Japan to reduce the uptake of radiocesium by crops. In this study, we examined the effects of two types of potassium fertilizers, potassium chloride (a readily available potassium fertilizer) and potassium silicate (a slow-release potassium fertilizer), as well as a split application of potassium, on the accumulation of 137 Cs by rice plants in two pot experiments. The 137 Cs concentrations in the brown rice and in the above-ground plants were significantly lower after potassium chloride application than after potassium silicate application. The potassium ion (K + ) concentrations in soil solutions sampled 9 and 21 d after transplanting were significantly higher for the potassium chloride application than for the potassium silicate application. The K + concentrations in soil solutions observed in the application of potassium silicate were similar to those in the treatment when no potassium was applied. This finding indicates that the application of potassium silicate did not sufficiently increase the available K + for rice plants in the soil, which led to a greater uptake of 137 Cs after the potassium silicate application than after the application of potassium chloride. The 137 Cs concentration in brown rice was higher in the split application of potassium fertilizer with the second application at the full heading stage than that without split application and the split application with the second application before heading. - Highlights: • Potassium application reduced 137 Cs uptake by rice grown in pot experiments. • Readily available K fertilizer more effectively decreased brown rice 137 Cs concentration. • Potassium should be applied before heading to reduce brown rice 137 Cs concentration.

Electrical properties of the potassium polytitanate compacts

International Nuclear Information System (INIS)

Goffman, V.G.; Gorokhovsky, A.V.; Kompan, M.M.; Tretyachenko, E.V.; Telegina, O.S.; Kovnev, A.V.; Fedorov, F.S.

2014-01-01

Highlights: • Quasi-static permittivity of potassium polytitanates compacts achieves 10 4 –10 5 . • Observed Maxwell–Wagner polarization attributes to layered structure of polytitanates. • The conductivity varies from 5 × 10 −2 to 10 −6 –10 −7 Sm/m in a wide range of temperatures. - Abstract: Titanates of alkali metals are widely applied materials as they are relatively low in cost and might be easily synthesized. They are utilized as adsorbents, catalysts, solid state electrolytes, superconductors. Here we report our results on electrical properties of the compacted amorphous potassium polytitanates powders. The electrical properties of the compacts were studied by means of complex impedance spectroscopy in a wide range of frequencies at different temperatures using two-electrode configuration. The frequency dependences of conductivity for the investigated potassium polytitanates compacts varies in the range from 5 × 10 −2 Sm/m (high frequencies, ion conductivity) up to 10 −6 –10 −7 Sm/m (low frequencies, electron conductivity) for a wide range of temperatures (19–150 °C). According to the results, at low frequencies quasi-static permittivity of the stabilized PPT compacts achieves high values of 10 4 –10 5 . This might be explained by Maxwell–Wagner polarization attributed to the layered structure of the potassium polytitanates particles containing potassium and hydronium ions together with crystallization water in the interlayer and is very promising for solid state electrolyte applications for moderate temperatures

General anaesthetics do not impair developmental expression of the KCC2 potassium-chloride cotransporter in neonatal rats during the brain growth spurt

KAUST Repository

Lacoh, Claudia Marvine

2013-03-26

BackgroundThe developmental transition from depolarizing to hyperpolarizing γ-aminobutyric acid-mediated neurotransmission is primarily mediated by an increase in the amount of the potassium-chloride cotransporter KCC2 during early postnatal life. However, it is not known whether early neuronal activity plays a modulatory role in the expression of total KCC2 mRNA and protein in the immature brain. As general anaesthetics are powerful modulators of neuronal activity, the purpose of this study was to explore how these drugs affect KCC2 expression during the brain growth spurt.MethodsWistar rat pups were exposed to either a single dose or 6 h of midazolam, propofol, or ketamine anaesthesia at postnatal days 0, 5, 10, or 15. KCC2 expression was assessed using immunoblotting, immunohistochemistry, or quantitative polymerase chain reaction analysis up to 3 days post-exposure in the medial prefrontal cortex.ResultsThere was a progressive and steep increase in the expression of KCC2 between birth and 2 weeks of age. Exposure to midazolam, propofol, or ketamine up to 6 h at any investigated stages of the brain growth spurt did not influence the expression of this cotransporter protein.ConclusionI.V. general anaesthetics do not seem to influence developmental expression of KCC2 during the brain growth spurt. © 2013 © The Author [2013].

Potassium sensing histidine kinase in Bacillus subtilis.

Science.gov (United States)

López, Daniel; Gontang, Erin A; Kolter, Roberto

2010-01-01

The soil-dwelling organism Bacillus subtilis is able to form multicellular aggregates known as biofilms. It was recently reported that the process of biofilm formation is activated in response to the presence of various, structurally diverse small-molecule natural products. All of these small-molecule natural products made pores in the membrane of the bacterium, causing the leakage of potassium cations from the cytoplasm of the cell. The potassium cation leakage was sensed by the membrane histidine kinase KinC, triggering the genetic pathway to the production of the extracellular matrix that holds cells within the biofilm. This chapter presents the methodology used to characterize the leakage of cytoplasmic potassium as the signal that induces biofilm formation in B. subtilis via activation of KinC. Development of novel techniques to monitor activation of gene expression in microbial populations led us to discover the differentiation of a subpopulation of cells specialized to produce the matrix that holds all cells together within the biofilm. This phenomenon of cell differentiation was previously missed by conventional techniques used to monitor transcriptional gene expression. Copyright © 2010 Elsevier Inc. All rights reserved.

Time-Dependent Antimicrobial Activity of Filtering Nonwovens with Gemini Surfactant-Based Biocides

Directory of Open Access Journals (Sweden)

Katarzyna Majchrzycka

2017-09-01

Full Text Available Previous studies on nonwovens used for respiratory protective devices (RPDs were related to equipment intended for short-term use. There is only limited research on the development of biocidal nonwoven fabrics for reusable RPDs that could be used safely in an industrial work environment where there is a risk of microbial growth. Moreover, a new group of biocides with high antimicrobial activity—gemini surfactants, has never been explored for textile’s application in previous studies. The aim of this study was to develop high-efficiency melt-blown nonwovens containing gemini surfactants with time-dependent biocidal activity, and to validate their antimicrobial properties under conditions simulating their use at a plant biomass-processing unit. A set of porous biocidal structures (SPBS was prepared and applied to the melt-blown polypropylene (PP nonwovens. The biocidal properties of the structures were triggered by humidity and had different activation rates. Scanning electron microscopy was used to undertake structural studies of the modified PP/SPBS nonwovens. In addition, simulation of plant biomass dust deposition on the nonwovens was performed. The biocidal activity of PP/SPBS nonwovens was evaluated following incubation with Escherichia coli and Aspergillus niger from the American Type Culture Collection, and with Pseudomonas fluorescens and Penicillium chrysogenum isolated from the biomass. PP/SPBS nonwovens exhibited antimicrobial activity to varying levels. Higher antimicrobial activity was noted for bacteria (R = 87.85–97.46% and lower for moulds (R = 80.11–94.53%.

Formulation and evaluation of sublingual tablets of losartan potassium

Directory of Open Access Journals (Sweden)

Nikunj J. Aghera

2012-05-01

Full Text Available Objective: Sublingual tablets of Losartan Potassium were prepared to improve its bioavailability, to avoid pre-systemic metabolism in the gastrointestinal tract and hepatic first pass elimination. Methods: The Sublingual tablets were prepared by direct compression procedure using different concentration of Starch 1500 and microcrystalline cellulose. Compatibility studies of drug and polymer were performed by FTIR spectroscopy and DSC. Preformulation property of API was evaluated. Postcompressional parameters such disintegration time, wetting time, water absorption ratio, in vitro drug release and in vivo bioavailability study of optimized formulation were determined. Results: FTIR spectroscopy and DSC study revealed that there was no possible interaction between drug and polymers. The precompression parameters were in acceptable range of pharmacopoeial specification. The disintegration time of optimized formulation (F3 was upto 48 sec. The in vitro release of Losartan Potassium was upto 15 min. The percentage relative bioavailability of Losartan Potassium from optimized sublingual tablets was found to be 144.7 %. Conclusions: Sublingual tablets of Losartan Potassium were successfully prepared with improved bioavailability.

Effect of potassium hydroxide activation in the desulfurization process of activated carbon prepared by sewage sludge and corn straw.

Science.gov (United States)

Zeng, Fan; Liao, Xiaofeng; Hu, Hui; Liao, Li

2018-03-01

Series sludge straw-based activated carbons were prepared by sewage sludge and corn straw with potassium hydroxide (KOH) activation, and the desulfurization performance of activated carbons was studied. To obtain the best desulfurization performance, the optimum ratio between the raw materials and the activator was investigated. The results showed that when the mass ratio of sewage sludge, corn straw, and KOH was 3:7:2, the activated carbon obtained the best breakthrough and saturation sulfur sorption capacities, which were 12.38 and 5.74 times, respectively, those of samples prepared by the nonactivated raw materials. The appropriate KOH could improve the microporosity and alkaline groups, meanwhile reducing the lactone groups, which were all beneficial to desulfurization performance. The chemical adsorption process of desulfurization can be simplified to four main steps, and the main desulfurization products are elemental sulfur and sulfate. Sewage sludge (SS) and corn straw (CS) both have great production and wide distribution and are readily available in China. Much attention has been paid on how to deal with them effectively. Based on the environment protection idea of waste treatment with waste and resource recycling, low-cost adsorbents were prepared by these processes. The proposed method can be expanded to the municipal solid waste recycling programs and renewable energy plan. Thus, proceeding with the study of preparing activated carbon by SS and straw as a carbon-based dry desulfurization agent could obtain huge social, economic, and environmental benefits.

The inhibitory effects of potassium chloride versus potassium silicate application on (137)Cs uptake by rice.

Science.gov (United States)

Fujimura, Shigeto; Yoshioka, Kunio; Ota, Takeshi; Ishikawa, Tetsuya; Sato, Makoto; Satou, Mutsuto

2016-03-01

After the accident at the Fukushima Dai-ichi Nuclear Power Plant owned by the Tokyo Electric Power Company on 11 March 2011, potassium fertilizer was applied to agricultural fields in the southern Tohoku and northern Kanto regions of Japan to reduce the uptake of radiocesium by crops. In this study, we examined the effects of two types of potassium fertilizers, potassium chloride (a readily available potassium fertilizer) and potassium silicate (a slow-release potassium fertilizer), as well as a split application of potassium, on the accumulation of (137)Cs by rice plants in two pot experiments. The (137)Cs concentrations in the brown rice and in the above-ground plants were significantly lower after potassium chloride application than after potassium silicate application. The potassium ion (K(+)) concentrations in soil solutions sampled 9 and 21 d after transplanting were significantly higher for the potassium chloride application than for the potassium silicate application. The K(+) concentrations in soil solutions observed in the application of potassium silicate were similar to those in the treatment when no potassium was applied. This finding indicates that the application of potassium silicate did not sufficiently increase the available K(+) for rice plants in the soil, which led to a greater uptake of (137)Cs after the potassium silicate application than after the application of potassium chloride. The (137)Cs concentration in brown rice was higher in the split application of potassium fertilizer with the second application at the full heading stage than that without split application and the split application with the second application before heading. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adiabatic theorem for the time-dependent wave operator

International Nuclear Information System (INIS)

Viennot, David; Jolicard, Georges; Killingbeck, John P.; Perrin, Marie-Yvonne

2005-01-01

The application of time-dependent wave operator theory to the development of a quantum adiabatic perturbation theory is treated both theoretically and numerically, with emphasis on the description of field-matter interactions which involve short laser pulses. It is first shown that the adiabatic limit of the time-dependent wave operator corresponds to a succession of instantaneous static Bloch wave operators. Wave operator theory is then shown to be compatible with the two-time Floquet theory of light-matter interaction, thus allowing the application of Floquet theory to cases which require the use of a degenerate active space. A numerical study of some problems shows that the perturbation strength associated with nonadiabatic processes can be reduced by using multidimensional active spaces and illustrates the capacity of the wave operator approach to produce a quasiadiabatic treatment of a nominally nonadiabatic Floquet dynamical system

Mechanisms of Dorsal Root Ganglion Stimulation in Pain Suppression: A Computational Modeling Analysis.

Science.gov (United States)

Kent, Alexander R; Min, Xiaoyi; Hogan, Quinn H; Kramer, Jeffery M

2018-04-01

The mechanisms of dorsal root ganglion (DRG) stimulation for chronic pain remain unclear. The objective of this work was to explore the neurophysiological effects of DRG stimulation using computational modeling. Electrical fields produced during DRG stimulation were calculated with finite element models, and were coupled to a validated biophysical model of a C-type primary sensory neuron. Intrinsic neuronal activity was introduced as a 4 Hz afferent signal or somatic ectopic firing. The transmembrane potential was measured along the neuron to determine the effect of stimulation on intrinsic activity across stimulation parameters, cell location/orientation, and membrane properties. The model was validated by showing close correspondence in action potential (AP) characteristics and firing patterns when compared to experimental measurements. Subsequently, the model output demonstrated that T-junction filtering was amplified with DRG stimulation, thereby blocking afferent signaling, with cathodic stimulation at amplitudes of 2.8-5.5 × stimulation threshold and frequencies above 2 Hz. This amplified filtering was dependent on the presence of calcium and calcium-dependent small-conductance potassium channels, which produced a hyperpolarization offset in the soma, stem, and T-junction with repeated somatic APs during stimulation. Additionally, DRG stimulation suppressed somatic ectopic activity by hyperpolarizing the soma with cathodic or anodic stimulation at amplitudes of 3-11 × threshold and frequencies above 2 Hz. These effects were dependent on the stem axon being relatively close to and oriented toward a stimulating contact. These results align with the working hypotheses on the mechanisms of DRG stimulation, and indicate the importance of stimulation amplitude, polarity, and cell location/orientation on neuronal responses. © 2018 International Neuromodulation Society.

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...

Thyroid hormone-dependent development of early cortical networks: Temporal specificity and the contribution of trkB and mTOR pathways

Directory of Open Access Journals (Sweden)

Sören eWesterholz

2013-08-01

Full Text Available Early in neocortical network development, triiodothyronine (T3 promotes GABAergic neurons’ population increase, their somatic growth and the formation of GABAergic synapses. In the presence of T3, GABAergic interneurons form longer axons and conspicuous axonal arborizations, with an increased number of putative synaptic boutons. Here we show that the increased GABAergic axonal growth is positively correlated with the proximity to non-GABAergic neurons. A differential innervation emerges from a T3-dependent decrease of axonal length in fields with low density of neuronal cell bodies, combined with an increased bouton formation in fields with high density of neuronal somata. T3 addition to deprived networks after the first two weeks of development did not rescue deficits in the GABAergic synaptic bouton distribution, or in the frequency and duration of spontaneous bursts. During the critical two-week-period, GABAergic signaling is depolarizing as revealed by calcium imaging experiments. Interestingly, T3 enhanced the expression of the potassium-chloride cotransporter 2 (KCC2, and accelerated the developmental shift from depolarizing to hyperpolarizing GABAergic signaling in non-GABAergic neurons.The T3-related increase of spontaneous network activity was remarkably reduced after blockade of either tropomyosin-receptor kinase B (trkB or mammalian target of rapamycin (mTOR pathways. T3-dependent increase in GABAergic neurons’ soma size was mediated mainly by mTOR signaling. Conversely, the T3-dependent selective increase of GABAergic boutons near non-GABAergic cell bodies is mediated by trkB signaling only. Both trkB and mTOR signaling mediate T3-dependent reduction of the GABAergic axon extension. The circuitry context is relevant for the interaction between T3 and trkB signaling, but not for the interactions between T3 and mTOR signaling.

Adaptation to Potassium-Limitation Is Essential for Acinetobacter baumannii Pneumonia Pathogenesis.

Science.gov (United States)

Samir, Reham; Hussein, Salma H; Elhosseiny, Noha M; Khattab, Marwa S; Shawky, Alaa E; Attia, Ahmed S

2016-12-15

 Acinetobacter baumannii is challenging the healthcare community as the cause of a wide range of untreatable infections. New targets need to be explored for the development of therapeutics.  The potassium-dependent protein (Kdp) system was investigated via bioinformatics and genetic tools. An isogenic mutant was constructed in kdpE and complemented in trans Gene expression and the ability to grow under potassium-limited conditions were investigated. Finally, the role of KdpE in virulence was examined in the murine pneumonia model.  The A. baumannii Kdp system has a distinct arrangement and is well conserved among A. baumannii strains. The genes encoding the 5 members of the system are transcriptionally linked. kdpE is upregulated >70-fold under potassium-limited conditions. The ΔkdpE mutant showed a significant growth defect under potassium-limited conditions and in the colonization of mice lungs. These defects could be restored upon introducing kdpE on a multiple-copy plasmid. Proteomic analyses indicated that KdpE could be regulating several proteins with potential involvement in pathogenesis.  For the first time, A. baumannii KdpE is shown to be crucial to pneumonia onset, and targeting this system can be a viable approach to treating these fatal infections. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Validating excised rodent lungs for functional hyperpolarized xenon-129 MRI.

Directory of Open Access Journals (Sweden)

David M L Lilburn

Full Text Available Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp (129Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp (129Xe. Straightforward hp (129Xe MRI protocols provide residual lung volume (RV data and permit for spatially resolved tracking of small hp (129Xe probe volumes during the inhalation cycle. Hp (129Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies.

Combined Hyperpolarized 13C-pyruvate MRS and 18F-FDG PET (HyperPET) Estimates of Glycolysis in Canine Cancer Patients

DEFF Research Database (Denmark)

Hansen, Adam E.; Gutte, Henrik; Holst, Pernille

2018-01-01

13C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized 13C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare hyperpol......13C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized 13C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare...

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.

Corrosion of nickel in potassium and sodium chloride melts containing vanadium trichloride

International Nuclear Information System (INIS)

Kochergin, V.P.; Ponomarev, Yu.S.; Bezvoritnij, V.A.; Bajbakov, D.P.

1976-01-01

Corrosion of nickel has been studied by the method of the rotating disc in melts of potassium and sodium chlorides containing vanadium trichloride in the concentration 0-20.0 wt.% in the temperature range 1103-1328 K. Corrosion proceeds in the diffusion region, the corrosion rate being controlled by diffusion of either V 3+ or V 2+ depending on the concentration of VCl 3 in the melts. The apparent activation energy of nickel corrosion is 43,110-74660 joule/mol

Role of hemolysis in potassium release by iodinated contrast medium

Energy Technology Data Exchange (ETDEWEB)

Hayakawa, K.; Nakamura, T.; Shimizu, Y. [Department of Radiology, Kyoto City Hospital (Japan)

1999-09-01

It has been demonstrated that an iodinated contrast medium (CM) causes release of potassium into blood vessel lumina, resulting in an increase in serum potassium. The purpose of the present study was to assess whether this potassium release is due to hemolysis. Fresh human blood was mixed in vitro with CM at a ratio of 10:2. Potassium release rates were determined, and serum haptoglobin and free hemoglobin were measured after 30 min of exposure to CM. To compare the potassium release curve between CM exposure and true hemolysis induced by distilled water, fresh human blood was also mixed with distilled water. The level of serum haptoglobin decreased due to hemodilution. Changes in haptoglobin were not correlated with potassium release rates. The serum free hemoglobin level did not increase significantly, and there was no correlation between changes in the free hemoglobin level and the rate of potassium release. Hemolysis caused by water occurred instantaneously, whereas potassium release caused by CM was a slow response, which was linearly correlated with exposure time. Potassium release from blood cannot be explained by hemolysis. (orig.) With 4 figs., 4 tabs., 3 refs.

Inhibitory effects of telmisartan on culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes from Xinjiang Kazakh patients with hypertension

Directory of Open Access Journals (Sweden)

Sha-Sha Huang

2016-10-01

Full Text Available Introduction: Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes derived from Xinjiang Kazakh patients with hypertension. Methods: CD4+ T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups. Changes in the expression levels of interleukin (IL-6 and IL-17 in the blood of the healthy control and case control subjects were detected by enzyme-linked immunosorbent assay. Peripheral blood CD4+ T lymphocytes were first activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Thereafter, changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and microscope photography. Changes in messenger RNA (mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and Western blots, respectively. Results: The IL-6 and IL-17 expression levels were significantly higher in the blood of the hypertensive Kazakh patients than in the healthy Kazakh people. Telmisartan inhibited T-lymphocytic proliferation, as well as the mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes, and the inhibitory effects were time-dependent, with the strongest inhibition observed after 48 h and significantly weaker inhibition observed after 24 h of treatment. Conclusions: Telmisartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and Kv1.3 potassium channel expression in CD4+ T lymphocytes.

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.

Oral potassium supplementation in surgical patients.

Science.gov (United States)

Hainsworth, Alison J; Gatenby, Piers A

2008-08-01

Hospital inpatients are frequently hypokalaemic. Low plasma potassium levels may cause life threatening complications, such as cardiac arrhythmias. Potassium supplementation may be administered parenterally or enterally. Oral potassium supplements have been associated with oesophageal ulceration, strictures and gastritis. An alternative to potassium salt tablets or solution is dietary modification with potassium rich food stuffs, which has been proven to be a safe and effective method for potassium supplementation. The potassium content of one medium banana is equivalent to a 12 mmol potassium salt tablet. Potassium supplementation by dietary modification has been shown to be equally efficacious to oral potassium salt supplementation and is preferred by the majority of patients. Subsequently, it is our practice to replace potassium using dietary modification, particularly in surgical patients having undergone oesophagogastrectomy or in those with peptic ulcer disease.

Acute afterload-imposed change in porcine cardiac metabolism imaged by hyperpolarized [1-13C]Pyruvate

DEFF Research Database (Denmark)

Tougaard, Rasmus Stilling; Søvsø Szocska Hansen, Esben; Laustsen, Christoffer

Deranged metabolism is now considered a key causal factor in heart failure and has therefore gained considerable scientific interest. The novel technique hyperpolarized MR has emerged as a leading methodological candidate to study these derangements. We employed a clinically relevant, large animal...

EFFECT OF METHANOLIC SEED EXTRACT OF PERSEA AMERICANA(AVOCADO PEAR ON PROTHROMBIN TIME AND ACTIVATED PARTIAL THROMBOPLASTIN TIME IN MICE

Directory of Open Access Journals (Sweden)

2016-11-01

Full Text Available Twenty (20 adult albino mice were used in the study to determine the effect of methanolic seed extract of Persea Americana on prothrombin time (PT and activated partial thromboplastin time (APTT test. The mice were obtained and kept for 2 weeks to acclimatize. They were weighed and divided into 5 groups. Group A served as control without the extract. Groups B to E were orally administered with graded doses of 200mg, 400 mg, 800 mg and 1600mg/kg body weight per mice daily for 28 days. Blood samples were collected through the median canthus into ti-sodium citrate anticoagulant containers for the analysis of PT and APTT, using standard operative procedure. The analysis was carried out at the Haematology Laboratory of University of Nigeria Teaching Hospital (UNTH Enugu. The results showed a prolonged APTT time at all the doses of the extract when compared with the control (P and lt;0.05. The prothrombin time at the dosage of 200mg/kg did not differ when compared with the control (P and gt;0.05. The increase in PT and APTT was dose dependent. This result pattern suggests that the extract causes prolonged prothrombin time and APTT at various concentrations possibly due to its high potassium content. The extract can be recommended in anticoagulant therapy since it prolongs PT and APTT.

Ruin Analysis of a Discrete-Time Dependent Sparre Andersen Model with External Financial Activities and Randomized Dividends

Directory of Open Access Journals (Sweden)

Sung Soo Kim

2016-02-01

Full Text Available We consider a discrete-time dependent Sparre Andersen risk model which incorporates multiple threshold levels characterizing an insurer’s minimal capital requirement, dividend paying situations, and external financial activities. We focus on the development of a recursive computational procedure to calculate the finite-time ruin probabilities and expected total discounted dividends paid prior to ruin associated with this model. We investigate several numerical examples and make some observations concerning the impact our threshold levels have on the finite-time ruin probabilities and expected total discounted dividends paid prior to ruin.

Mass-spectrometric study of thermodynamics of molybdate potassium evaporation

International Nuclear Information System (INIS)

Kazenas, E.K.; Tsvetkov, Yu.V.; Samojlova, I.O.; Astakhova, G.K.; Petrov, A.A.

2002-01-01

One investigated into evaporation of potassium molybdate within 1170-1310 K temperature range using platinum effusion chambers. Evaporation of potassium molybdate within 1170-1310 K temperature range may be described as follows: K 2 MoO 4(s,l) = K 2 MoO 4(g) . Based on method of least squares one calculated equation of K 2 MoO 4(g) vapor pressure (pressure in millimeters of mercury column) dependence on temperature for 1200-1320 K range. One evaluated value of K 2 MoO 4(g) molecule atomization energy [ru

Electrical properties of the potassium polytitanate compacts

Energy Technology Data Exchange (ETDEWEB)

Goffman, V.G.; Gorokhovsky, A.V. [NanoTechProm Ltd., Saratov (Russian Federation); Saratov State Technical University, Saratov (Russian Federation); Kompan, M.M. [Physico-Technical Institute of the Russian Academy of Science, St. Petersburg (Russian Federation); Tretyachenko, E.V.; Telegina, O.S.; Kovnev, A.V. [NanoTechProm Ltd., Saratov (Russian Federation); Saratov State Technical University, Saratov (Russian Federation); Fedorov, F.S., E-mail: fedorov_fs@daad-alumni.de [NanoTechProm Ltd., Saratov (Russian Federation); Saratov State Technical University, Saratov (Russian Federation)

2014-12-05

Highlights: • Quasi-static permittivity of potassium polytitanates compacts achieves 10{sup 4}–10{sup 5}. • Observed Maxwell–Wagner polarization attributes to layered structure of polytitanates. • The conductivity varies from 5 × 10{sup −2} to 10{sup −6}–10{sup −7} Sm/m in a wide range of temperatures. - Abstract: Titanates of alkali metals are widely applied materials as they are relatively low in cost and might be easily synthesized. They are utilized as adsorbents, catalysts, solid state electrolytes, superconductors. Here we report our results on electrical properties of the compacted amorphous potassium polytitanates powders. The electrical properties of the compacts were studied by means of complex impedance spectroscopy in a wide range of frequencies at different temperatures using two-electrode configuration. The frequency dependences of conductivity for the investigated potassium polytitanates compacts varies in the range from 5 × 10{sup −2} Sm/m (high frequencies, ion conductivity) up to 10{sup −6}–10{sup −7} Sm/m (low frequencies, electron conductivity) for a wide range of temperatures (19–150 °C). According to the results, at low frequencies quasi-static permittivity of the stabilized PPT compacts achieves high values of 10{sup 4}–10{sup 5}. This might be explained by Maxwell–Wagner polarization attributed to the layered structure of the potassium polytitanates particles containing potassium and hydronium ions together with crystallization water in the interlayer and is very promising for solid state electrolyte applications for moderate temperatures.

Activation of the Na+/K(+)-pump in rat peritoneal mast cells following histamine release: a possible role in cell recovery

DEFF Research Database (Denmark)

Knudsen, T; Ferjan, I; Johansen, Torben

1993-01-01

1. The activity of the Na+/K(+)-pump in rat peritoneal mast cells was measured at various time intervals after induction of cellular histamine release by compound 48/80 or by the antigen-antibody reaction. The Na+/K(+)-pump activity was assessed as the ouabain-sensitive potassium uptake....... On the basis of the present results, we suggest a role for the Na+/K(+)-pump in the recovery process of the mast cell following histamine release....... of the cells using 86Rb+ as a tracer for potassium (K+(86Rb+)-uptake). 2. Stimulation of the cells with compound 48/80 induced a time and concentration dependent increase of the Na+/K(+)-pump activity. The pump activity was maximal 2 min after stimulation of the cells. Then, the activity gradually decreased...

Mechanisms of hyperpolarization in regenerated mature motor axons in cat

DEFF Research Database (Denmark)

Moldovan, Mihai; Krarup, Christian

2004-01-01

We found persistent abnormalities in the recovery of membrane excitability in long-term regenerated motor nerve fibres in the cat as indicated in the companion paper. These abnormalities could partly be explained by membrane hyperpolarization. To further investigate this possibility, we compared...... the changes in excitability in control nerves and long-term regenerated cat nerves (3-5 years after tibial nerve crush) during manoeuvres known to alter axonal membrane Na(+)-K(+) pump function: polarization, cooling to 20 degrees C, reperfusion after 10 min ischaemia, and up to 60 s of repetitive stimulation...

Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.

Science.gov (United States)

Higaki, Kazutaka; Choe, Sally Y; Löbenberg, Raimar; Welage, Lynda S; Amidon, Gordon L

2008-09-01

The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine.

Effects of water soaking and/or sodium polystyrene sulfonate addition on potassium content of foods.

Science.gov (United States)

Picq, Christian; Asplanato, Marion; Bernillon, Noémie; Fabre, Claudie; Roubeix, Mathilde; Ricort, Jean-Marc

2014-09-01

In this study, we determined, by atomic absorption spectrophotometry, the potassium amount leached by soaking or boiling foods identified by children suffering from chronic renal failure as "pleasure food" and that they cannot eat because of their low-potassium diet, and evaluated whether addition of sodium polystyrene sulfonate resin (i.e. Kayexalate®) during soaking or boiling modulated potassium loss. A significant amount of potassium content was removed by soaking (16% for chocolate and potato, 26% for apple, 37% for tomato and 41% for banana) or boiling in a large amount of water (73% for potato). Although Kayexalate® efficiently dose-dependently removed potassium from drinks (by 48% to 73%), resin addition during soaking or boiling did not eliminate more potassium from solid foods. Our results therefore provide useful information for dietitians who elaborate menus for people on potassium-restricted diets and would give an interesting alternative to the systematic elimination of all potassium-rich foods from their diet.

Microinjection study on potassium transport of rat kidney

International Nuclear Information System (INIS)

Miyamoto, Makoto

1978-01-01

Wister rate were divided into the following four groups. (A) control group (B) high-potassium diet group (C) low-potassium diet group (D) nephron population reduction (N.P.R.) group. Microinjection of the artificial solutions containing both 86 Rb and 3 H-inulin were performed into the proximal and distal convoluted tubules as well as cortical peritubular capillaries in rats undergoing mannitol diuresis. Excretory patterns of these substances were analyzed in successive urine samples. 3 H-inulin is entirely recovered in the urine of the experimental kidney following the injection into the proximal and distal tubules. 86 Rb is an adequate tracer for potassium and is absorbed into the potassium pool from either proximal tubular injections or peritubular capillaries. 86 Rb excreted with a time course similar to that of 3 H-inulin is termed as 'direct recovery' and that excreted more slowly, 'delayed recovery'. The 86 Rb recoveries which were obtained after proximal injections were independent of the injection site and averaged 9%. Secretion of 86 Rb into the urine was stimulate during enhanced K secretion and decreased during reduced K secretion along the distal nephron. Distal tubular injections gave 100% direct recovery in control, high-K diet, and N.P.R. rats. It was apparent that the 86 Rb recovery was significantly reduced, although not delayed, in animals deprived of dietary potassium for several weeks. At the collecting duct, the extensive net potassium reabsorption is observed in potassium depleted rats, whereas K absorption might be reduced or even secretion is seemingly taking place in potassium loading rats. In conclution, distal convolution and collecting duct play the major role in the regulation of urinary potassium excretion. (auth.)

Probing early tumor response to radiation therapy using hyperpolarized [1-¹³C]pyruvate in MDA-MB-231 xenografts.

Directory of Open Access Journals (Sweden)

Albert P Chen

Full Text Available Following radiation therapy (RT, tumor morphology may remain unchanged for days and sometimes weeks, rendering anatomical imaging methods inadequate for early detection of therapeutic response. Changes in the hyperpolarized [1-¹³C]lactate signals observed in vivo following injection of pre-polarized [1-¹³C]pyruvate has recently been shown to be a marker for tumor progression or early treatment response. In this study, the feasibility of using ¹³C metabolic imaging with [1-¹³C]pyruvate to detect early radiation treatment response in a breast cancer xenograft model was demonstrated in vivo and in vitro. Significant decreases in hyperpolarized [1-¹³C]lactate relative to [1-¹³C]pyruvate were observed in MDA-MB-231 tumors 96 hrs following a single dose of ionizing radiation. Histopathologic data from the treated tumors showed higher cellular apoptosis and senescence; and changes in the expression of membrane monocarboxylate transporters and lactate dehydrogenase B were also observed. Hyperpolarized ¹³C metabolic imaging may be a promising new tool to develop novel and adaptive therapeutic regimens for patients undergoing RT.

Degradation behaviour of potassium K-phosphite in apple trees

OpenAIRE

Kelderer, Markus; Matteazzi, Aldo; Casera, Claudio

2008-01-01

Although potassium phosphite is not registered for organic fruit production in Europe, it has long been regarded as a potential alternative to sulphur- and copper-containing fungicides. In 2005/2006 a field trial was carried out to verify the presence of residues of phosphoric acid over time in apples after applications of potassium phosphite at different time-points. No residues were present on fruits if treatments were applied before flowering, whereas treatments after flower...

Time-dependent Autler-Townes spectroscopy

International Nuclear Information System (INIS)

Qamar, Sajid; Zhu, S.-Y.; Zubairy, M Suhail

2003-01-01

Autler-Townes spontaneous emission spectroscopy is revisited for a time-dependent case. We report the results of spontaneous emission spectra for nonstationary scattered light signals using the definition of the time-dependent physical spectrum. This is a rare example of problems where time-dependent spectra can be calculated exactly

Time-dependent Autler-Townes spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Qamar, Sajid [Institute for Quantum Studies, Department of Physics, Texas A and M University, College Station, TX 77843-4242 (United States); Zhu, S.-Y. [Institute for Quantum Studies, Department of Physics, Texas A and M University, College Station, TX 77843-4242 (United States); Zubairy, M Suhail [Institute for Quantum Studies, Department of Physics, Texas A and M University, College Station, TX 77843-4242 (United States)

2003-04-01

Autler-Townes spontaneous emission spectroscopy is revisited for a time-dependent case. We report the results of spontaneous emission spectra for nonstationary scattered light signals using the definition of the time-dependent physical spectrum. This is a rare example of problems where time-dependent spectra can be calculated exactly.

Time-dependent behavior of concrete

International Nuclear Information System (INIS)

Pfeiffer, P.A.; Tanabe, Tada-aki

1992-01-01

This paper is a condensed version of the material presented at the International Workshop on Finite Element Analysis of Reinforced Concrete, Session 4 -- Time Dependent Behavior, held at Columbia University, New York on June 3--6, 1991. Dr. P.A. Pfeiffer presented recent developments in time-dependent behavior of concrete and Professor T. Tanabe presented a review of research in Japan on time-dependent behavior of concrete. The paper discusses the recent research of time-dependent behavior of concrete in the past few years. 6 refs

Opium can differently alter blood glucose, sodium and potassium in male and female rats.

Science.gov (United States)

Karam, Gholamreza Asadi; Rashidinejad, Hamid Reza; Aghaee, Mohammad Mehdi; Ahmadi, Jafar; Rahmani, Mohammad Reza; Mahmoodi, Mehdi; Azin, Hosein; Mirzaee, Mohammad Reza; Khaksari, Mohammad

2008-04-01

To determine the effects of opium on serum glucose, potassium and sodium in male and female Wistar rat, opium solution (60 mg/kg) injected intraperitoneally and the same volume of distilled water was used as control (7 rats in each group). Blood samples were collected at 0, 30, 60, 120, 240 and 360 minutes after injection from orbit cavity and the values of serum glucose, sodium (Na(+)) and potassium (K(+)) were measured. The data were then analyzed by the repeated measure ANOVA based on sex and case-control group. P opium solution injection, in female rats compared to a control group. However, the male rats had this rise at 30, 60 and 120 minutes after opium solution injection compared to control group. While serum glucose in male rats was significantly higher than females at 30, 60 and 120 minutes, this value was higher in the female rats at 360 minutes. Therefore, serum glucose alterations following opium injection was significantly different in groups and in the sexes at different times. Sodium (Na(+)) rose at 60, 240 and 360 minutes significantly in all rats compared to control group. However, sodium alteration following opium injection was significantly different only between treated and control groups but sex-independent at all times. Potassium (K(+)) increased significantly at 60, 120, 240 and 360 minutes in male rats, compared to a control group. In female rats K(+) significantly raised at 30, 120, 240 and 360 minutes. Therefore, the alteration of K(+) in male and female rats was found time dependent and sex independent. According to our results, opium increased serum glucose in male and female rats differently, and it interferes with metabolic pathways differently on a gender dependent basis. Opium raised serum Na(+) and K(+), thus it interfere with water regulation and blood pressure via different mechanism.

Imaging cerebral 2-ketoisocaproate metabolism with hyperpolarized (13)C Magnetic Resonance Spectroscopic Imaging

DEFF Research Database (Denmark)

Butt, Sadia Asghar; Søgaard, Lise Vejby-Christensen; Magnusson, Peter O.

2012-01-01

The branched chain amino acid transaminase (BCAT) has an important role in nitrogen shuttling and glutamate metabolism in the brain. The purpose of this study was to describe the cerebral distribution and metabolism of hyperpolarized 2-keto[1-(13)C]isocaproate (KIC) in the normal rat using magnet...... & Metabolism advance online publication, 28 March 2012; doi:10.1038/jcbfm.2012.34....

Measurement of whole body cellular and collagen nitrogen, potassium, and other elements by neutron activation and whole body counting

International Nuclear Information System (INIS)

James, H.M.; Fabricius, P.J.; Dykes, P.W.

1987-01-01

Whole body nitrogen can be measured by neutron activation analysis with an acceptable radiation dose; it is an index of body protein which, in normal subjects, is 65% cellular protein and 35% extracellular connective collagen. Whole body potassium can be measured by whole body counting without irradiating the subject; it is an index of body cell mass. We measured whole body nitrogen, potassium, extracellular water, intracellular water, and fat-folds. The differences between 37 malnourished patients and five normal subjects suggested that the patients had 9 kg less cell mass than normal, but no difference in extracellular mass. Measurements were made on eight patients before and after 14 days of total parenteral nutrition; balance of nitrogen intake and excretion also was measured. The changes were consistent with mean increases of 3 kg of cellular mass and 3 kg of fat with no change of extracellular mass. The accuracy and sensitivity of the whole body measurements need further confirmation for use in patients with changing body composition. Where tissue wasting is largely from the cellular compartment, potassium could be a more sensitive index of wasting than nitrogen. Multielement analysis of nitrogen, potassium, chlorine, and carbon will probably be valuable in elucidating body composition in malnutrition

Crystal structure transformation in potassium acrylate

Science.gov (United States)

Pai Verneker, V. R.; Vasanthakumari, R.

1983-10-01

Potassium acrylate undergoes a reversible phase transformation around 335°K with an activation energy of 133 kcal/mole. Differential scanning calorimetry and high temperature X-ray powder diffraction techniques have been used to probe this phenomenon.

Sterically screened halogenocyclobutanones. I. Transformations of cyclopropyl-substituted 2,2-dichlorocyclobutanones under the influence of potassium hydroxide

International Nuclear Information System (INIS)

Donskaya, N.A.; Bessmertnykh, A.G.; Drobysh, V.A.; Shabarov, Yu.S.

1987-01-01

The reaction of 2,2-dichloro-3-cyclopropylcyclobutanones with potassium hydroxide was studied. The direction of the reaction depends on the concentration of the potassium hydroxide; with a 2% solution of potassium hydroxide 4,4-dichlorobutyric acids are formed with yields of up to 80%, and with a 15% solution of potassium hydroxide 5-hydroxydihydro-2-furanones are formed with yields of up to 80%. Proposals are made about the mechanism of formation of 5-hydroxydihydro-2-furanones

Insulin and IGF-1 activate Kir4.1/5.1 channels in cortical collecting duct principal cells to control basolateral membrane voltage.

Science.gov (United States)

Zaika, Oleg; Palygin, Oleg; Tomilin, Viktor; Mamenko, Mykola; Staruschenko, Alexander; Pochynyuk, Oleh

2016-02-15

Potassium Kir4.1/5.1 channels are abundantly expressed at the basolateral membrane of principal cells in the cortical collecting duct (CCD), where they are thought to modulate transport rates by controlling transepithelial voltage. Insulin and insulin-like growth factor-1 (IGF-1) stimulate apically localized epithelial sodium channels (ENaC) to augment sodium reabsorption in the CCD. However, little is known about their actions on potassium channels localized at the basolateral membrane. In this study, we implemented patch-clamp analysis in freshly isolated murine CCD to assess the effect of these hormones on Kir4.1/5.1 at both single channel and cellular levels. We demonstrated that K(+)-selective conductance via Kir4.1/5.1 is the major contributor to the macroscopic current recorded from the basolateral side in principal cells. Acute treatment with 10 μM amiloride (ENaC blocker), 100 nM tertiapin-Q (TPNQ; ROMK inhibitor), and 100 μM ouabain (Na(+)-K(+)-ATPase blocker) failed to produce a measurable effect on the macroscopic current. In contrast, Kir4.1 inhibitor nortriptyline (100 μM), but not fluoxetine (100 μM), virtually abolished whole cell K(+)-selective conductance. Insulin (100 nM) markedly increased the open probability of Kir4.1/5.1 and nortriptyline-sensitive whole cell current, leading to significant hyperpolarization of the basolateral membrane. Inhibition of the phosphatidylinositol 3-kinase cascade with LY294002 (20 μM) abolished action of insulin on Kir4.1/5.1. IGF-1 had similar stimulatory actions on Kir4.1/5.1-mediated conductance only when applied at a higher (500 nM) concentration and was ineffective at 100 nM. We concluded that both insulin and, to a lesser extent, IGF-1 activate Kir4.1/5.1 channel activity and open probability to hyperpolarize the basolateral membrane, thereby facilitating Na(+) reabsorption in the CCD. Copyright © 2016 the American Physiological Society.

Regional alveolar partial pressure of oxygen measurement with parallel accelerated hyperpolarized gas MRI.

Science.gov (United States)

Kadlecek, Stephen; Hamedani, Hooman; Xu, Yinan; Emami, Kiarash; Xin, Yi; Ishii, Masaru; Rizi, Rahim

2013-10-01

Alveolar oxygen tension (Pao2) is sensitive to the interplay between local ventilation, perfusion, and alveolar-capillary membrane permeability, and thus reflects physiologic heterogeneity of healthy and diseased lung function. Several hyperpolarized helium ((3)He) magnetic resonance imaging (MRI)-based Pao2 mapping techniques have been reported, and considerable effort has gone toward reducing Pao2 measurement error. We present a new Pao2 imaging scheme, using parallel accelerated MRI, which significantly reduces measurement error. The proposed Pao2 mapping scheme was computer-simulated and was tested on both phantoms and five human subjects. Where possible, correspondence between actual local oxygen concentration and derived values was assessed for both bias (deviation from the true mean) and imaging artifact (deviation from the true spatial distribution). Phantom experiments demonstrated a significantly reduced coefficient of variation using the accelerated scheme. Simulation results support this observation and predict that correspondence between the true spatial distribution and the derived map is always superior using the accelerated scheme, although the improvement becomes less significant as the signal-to-noise ratio increases. Paired measurements in the human subjects, comparing accelerated and fully sampled schemes, show a reduced Pao2 distribution width for 41 of 46 slices. In contrast to proton MRI, acceleration of hyperpolarized imaging has no signal-to-noise penalty; its use in Pao2 measurement is therefore always beneficial. Comparison of multiple schemes shows that the benefit arises from a longer time-base during which oxygen-induced depolarization modifies the signal strength. Demonstration of the accelerated technique in human studies shows the feasibility of the method and suggests that measurement error is reduced here as well, particularly at low signal-to-noise levels. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

Penicillin V Potassium

Science.gov (United States)

Penicillin V potassium is used to treat certain infections caused by bacteria such as pneumonia and other ... heart valves and other symptoms) from coming back. Penicillin V potassium is in a class of medications ...

Evaluation of the potassium adsorption capacity of a potassium adsorption filter during rapid blood transfusion.

Science.gov (United States)

Matsuura, H; Akatsuka, Y; Muramatsu, C; Isogai, S; Sugiura, Y; Arakawa, S; Murayama, M; Kurahashi, M; Takasuga, H; Oshige, T; Yuba, T; Mizuta, S; Emi, N

2015-05-01

The concentration of extracellular potassium in red blood cell concentrates (RCCs) increases during storage, leading to risk of hyperkalemia. A potassium adsorption filter (PAF) can eliminate the potassium at normal blood transfusion. This study aimed to investigate the potassium adsorption capacity of a PAF during rapid blood transfusion. We tested several different potassium concentrations under a rapid transfusion condition using a pressure bag. The adsorption rates of the 70-mEq/l model were 76·8%. The PAF showed good potassium adsorption capacity, suggesting that this filter may provide a convenient method to prevent hyperkalemia during rapid blood transfusion. © 2015 International Society of Blood Transfusion.

Pulmonary hyperpolarized (129) Xe morphometry for mapping xenon gas concentrations and alveolar oxygen partial pressure: Proof-of-concept demonstration in healthy and COPD subjects.

Science.gov (United States)

Ouriadov, A; Farag, A; Kirby, M; McCormack, D G; Parraga, G; Santyr, G E

2015-12-01

Diffusion-weighted (DW) hyperpolarized (129) Xe morphometry magnetic resonance imaging (MRI) can be used to map regional differences in lung tissue micro-structure. We aimed to generate absolute xenon concentration ([Xe]) and alveolar oxygen partial pressure (pA O2 ) maps by extracting the unrestricted diffusion coefficient (D0 ) of xenon as a morphometric parameter. In this proof-of-concept demonstration, morphometry was performed using multi b-value (0, 12, 20, 30 s/cm(2) ) DW hyperpolarized (129) Xe images obtained in four never-smokers and four COPD ex-smokers. Morphometric parameters and D0 maps were computed and the latter used to generate [Xe] and pA O2 maps. Xenon concentration phantoms estimating a range of values mimicking those observed in vivo were also investigated. Xenon D0 was significantly increased (P = 0.035) in COPD (0.14 ± 0.03 cm(2) /s) compared with never-smokers (0.12 ± 0.02 cm(2) /s). COPD ex-smokers also had significantly decreased [Xe] (COPD = 8 ± 7% versus never-smokers = 13 ± 8%, P = 0.012) and increased pA O2 (COPD = 18 ± 3% versus never-smokers = 15 ± 3%, P = 0.009) compared with never-smokers. Phantom measurements showed the expected dependence of D0 on [Xe] over the range of concentrations anticipated in vivo. DW hyperpolarized (129) Xe MRI morphometry can be used to simultaneously map [Xe] and pA O2 in addition to providing micro-structural biomarkers of emphysematous destruction in COPD. Phantom measurements of D0 ([Xe]) supported the hypotheses that differences in subjects may reflect differences in functional residual capacity. © 2014 Wiley Periodicals, Inc.

Cholesterol influences voltage-gated calcium channels and BK-type potassium channels in auditory hair cells.

Directory of Open Access Journals (Sweden)

Erin K Purcell

Full Text Available The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage-gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitability are unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MβCD on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage-gated calcium channels (VGCCs are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type potassium current by 50% in chick cochlear hair cells. In contrast, MβCD treatment increased peak inward calcium current (~30%, ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol-enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology.

Real time process algebra with time-dependent conditions

NARCIS (Netherlands)

Baeten, J.C.M.; Middelburg, C.A.

We extend the main real time version of ACP presented in [6] with conditionals in which the condition depends on time. This extension facilitates flexible dependence of proccess behaviour on initialization time. We show that the conditions concerned generalize the conditions introduced earlier

Potassium maldistribution revisited

African Journals Online (AJOL)

Background:This study investigated maldistribution of concentrated 15% potassium chloride after injection into .... and latter experiments referred to for example as “Control 1” ..... be further investigated as a reliable, simple method of potassium.

Dependable Real-Time Systems

Science.gov (United States)

1991-09-30

0196 or 413 545-0720 PI E-mail Address: krithi@nirvan.cs.umass.edu, stankovic(ocs.umass.edu Grant or Contract Title: Dependable Real - Time Systems Grant...Dependable Real - Time Systems " Grant or Contract Number: N00014-85-k-0398 L " Reporting Period: 1 Oct 87 - 30 Sep 91 , 2. Summary of Accomplishments ’ 2.1 Our...in developing a sound approach to scheduling tasks in complex real - time systems , (2) developed a real-time operating system kernel, a preliminary

Cytoplasmic Domains and Voltage-Dependent Potassium Channel Gating

Science.gov (United States)

Barros, Francisco; Domínguez, Pedro; de la Peña, Pilar

2012-01-01

The basic architecture of the voltage-dependent K+ channels (Kv channels) corresponds to a transmembrane protein core in which the permeation pore, the voltage-sensing components and the gating machinery (cytoplasmic facing gate and sensor–gate coupler) reside. Usually, large protein tails are attached to this core, hanging toward the inside of the cell. These cytoplasmic regions are essential for normal channel function and, due to their accessibility to the cytoplasmic environment, constitute obvious targets for cell-physiological control of channel behavior. Here we review the present knowledge about the molecular organization of these intracellular channel regions and their role in both setting and controlling Kv voltage-dependent gating properties. This includes the influence that they exert on Kv rapid/N-type inactivation and on activation/deactivation gating of Shaker-like and eag-type Kv channels. Some illustrative examples about the relevance of these cytoplasmic domains determining the possibilities for modulation of Kv channel gating by cellular components are also considered. PMID:22470342

Holographic complexity for time-dependent backgrounds

Energy Technology Data Exchange (ETDEWEB)

Momeni, Davood, E-mail: davoodmomeni78@gmail.com [Eurasian International Center for Theoretical Physics and Department of General Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan); Faizal, Mir, E-mail: mirfaizalmir@googlemail.com [Irving K. Barber School of Arts and Sciences, University of British Columbia, Okanagan, 3333 University Way, Kelowna, British Columbia V1V 1V7 (Canada); Department of Physics and Astronomy, University of Lethbridge, Lethbridge, Alberta, T1K 3M4 (Canada); Bahamonde, Sebastian, E-mail: sebastian.beltran.14@ucl.ac.uk [Department of Mathematics, University College London, Gower Street, London, WC1E 6BT (United Kingdom); Myrzakulov, Ratbay [Eurasian International Center for Theoretical Physics and Department of General Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan)

2016-11-10

In this paper, we will analyze the holographic complexity for time-dependent asymptotically AdS geometries. We will first use a covariant zero mean curvature slicing of the time-dependent bulk geometries, and then use this co-dimension one spacelike slice of the bulk spacetime to define a co-dimension two minimal surface. The time-dependent holographic complexity will be defined using the volume enclosed by this minimal surface. This time-dependent holographic complexity will reduce to the usual holographic complexity for static geometries. We will analyze the time-dependence as a perturbation of the asymptotically AdS geometries. Thus, we will obtain time-dependent asymptotically AdS geometries, and we will calculate the holographic complexity for such time-dependent geometries.

Na+ -K+ pump activity in rat peritoneal mast cells: inhibition by extracellular calcium

DEFF Research Database (Denmark)

Knudsen, Torben; Johansen, Torben

1989-01-01

1. Pure populations of rat peritoneal mast cells were used to study cellular potassium uptake. The radioactive potassium analogue, 86rubidium, was used as a tracer for potassium for measurements of the activity of the cellular potassium uptake process. 2. The ouabain-sensitive and the ouabain......-resistant potassium (86rubidium) uptake of mast cells incubated in the presence of calcium, 1 mmol l-1, were very low, 52 and 147 pmol per 10(6) cells min-1. 3. Calcium-deprivation of the cells uncovered a large capacity ouabain-sensitive potassium (86rubidium) uptake mechanism. The activity of the uptake mechanism...... was decreased by reintroduction of calcium into the cell suspension, and it was dependent on cellular energy metabolism, temperature and pH. 4. The potassium (86rubidium) uptake of mast cells incubated in a calcium-free medium occurs through an active and ouabain-sensitive mechanism that has the nature...

21 CFR 184.1619 - Potassium carbonate.

Science.gov (United States)

2010-04-01

... solution of potassium hydroxide with excess carbon dioxide to produce potassium carbonate; (3) By treating a solution of potassium hydroxide with carbon dioxide to produce potassium bicarbonate, which is... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium carbonate. 184.1619 Section 184.1619 Food...

Potassium/sodium ion exchange of sodium aluminosilicate and soda-lime glasses with potassium nitrate melts

International Nuclear Information System (INIS)

Richter, E.

1983-08-01

The alkali self-diffusion coefficients, the concentration-dependent interdiffusion coefficients, and the actual equilibrium constants of the ion exchange process were determinated for model glasses of the Na 2 O-Al 2 O 3 -SiO 2 type and the Na 2 O-CaO-SiO 2 type by nuclear techniques. The measured self-diffusion data and interdiffusion coefficients were used to estimate the stress profiles initiated by the K/Na exchange below the transformation temperature in the surface region. The activation volume of the sodium and potassium ions for diffusion through the surface zone stressed by ion exchange was determined. The disturbing influence of small concentrations of determined divalent cations in KNO 3 (especially Ca 2+ ) was investigated and thermodynamically described. Possibilities were demonstrated to remove these disturbances by anionic admixtures to the KNO 3 melt. Conclusions were drawn for the technical process of the chemical strengthening of glass by K/Na ion exchange at lower temperatures. (author)

Active biodegradable films produced with blends of rice flour and poly(butylene adipate co-terephthalate): effect of potassium sorbate on film characteristics.

Science.gov (United States)

Sousa, G M; Soares Júnior, M S; Yamashita, F

2013-08-01

The objective of work was to produce and characterize biodegradable films from rice flour, poly(butylene adipate co-terephthalate) (PBAT), glycerol and potassium sorbate, for application as active packaging for fresh lasagna pasta. The films were evaluated with respect to their optical, water vapor barrier, mechanical and microstructural properties. The mechanical properties and microstructure were evaluated after use as packaging material for fresh pasta for 45 days at 7°C. The blends of rice flour, PBAT, glycerol and potassium sorbate showed good processability and allowed for the pilot scale production of films by blow extrusion process. The addition of 1 to 5% potassium sorbate as plasticizer agent of films in place of glycerol did not alter the film mechanical properties and a sorbate concentration greater or equal than 3% reduced the opacity, although increasing the water vapor permeability. The films could be used as active packaging for fresh food pasta, since they remained integral and easy to handle after application. The rice flour was shown to be an excellent material for the formulation of biodegradable films, since it is a low-cost raw material from a renewable source. The addition of potassium sorbate did not affect the extrusion process, and could be used in the production of packaging for use with foods. Copyright © 2013 Elsevier B.V. All rights reserved.

In vivo single-shot (13)C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding

DEFF Research Database (Denmark)

Schmidt, Rita; Laustsen, Christoffer; Dumez, Jean-Nicolas

2014-01-01

are necessary. Several approaches have been customized for hyperpolarized (13)C MRI, including CSI with a center-out k-space encoding, EPSI, and spectrally selective pulses in combination with spiral EPI acquisitions. Recent studies have described the potential of single-shot alternatives based...... temporal) data sets were obtained at 7T from a murine lymphoma tumor model....

Potassium supplements for oral diarrhoea regimens.

Science.gov (United States)

Clements, M L; Levine, M M; Black, R E; Hughes, T P; Rust, J; Tome, F C

1980-10-18

A study is proposed for supplementing potassium loss from diarrhea in rehydration therapies with fresh fruit and other naturally potassium-rich foods. Bananas contain .1 mol of potassium per gm. Freshly squeezed lemon or orange juices were tested for potassium and sodium content and found to have very low potassium concentration. Therefore, the banana was chosen for an upcoming study that will determine if infants and children suffering from diarrhea can ingest the amounts of the fruit necessary to elevate the potassium level sufficiently. Bananas as the potassium source are thought to be well-accepted in developing areas.

Potassium adsorption ratios as an indicator for the fate of agricultural potassium in groundwater

NARCIS (Netherlands)

Griffioen, J.

2001-01-01

Fertilization of agricultural land in groundwater infiltration areas often causes deterioration of groundwater quality. In addition to nitrogen and phosphorous, potassium deserves attention. The fate of potassium in the subsurface is controlled mainly by cation-exchange. Use of the Potassium

Topic 5: Time-Dependent Behavior

International Nuclear Information System (INIS)

Pfeiffer, P.A.; Tanabe, Tada-aki

1991-01-01

This chapter is a report of the material presented at the International Workshop on Finite Element Analysis of Reinforced Concrete, Session 4 -- Time Dependent Behavior, held at Columbia University, New York on June 3--6, 1991. Dr. P.A. Pfeiffer presented recent developments in time-dependent behavior of concrete and Professor T. Tanabe presented a review of research in Japan on time-dependent behavior of concrete. The chapter discusses the recent research of time-dependent behavior of concrete in the past few years in both the USA-European and Japanese communities. The author appreciates the valuable information provided by Zdenek P. Bazant in preparing the USA-European Research section

The mode of inhibition of the Na+-K+ pump activity in mast cells by calcium

DEFF Research Database (Denmark)

Knudsen, T; Johansen, Torben

1989-01-01

, and hence the pump activity. This hypothesis is supported by the stimulation of pump activity produced by monensin, which is not inhibited by calcium. The enhancement of pump activity after exposure of calcium-deprived cells to EGTA might be the result of a further increase in the sodium permeability......1 The inhibition by calcium of the Na(+)-K+ pump in the plasma membrane of rat peritoneal mast cells was studied in pure populations of the cells by measuring the ouabain-sensitive uptake of the radioactive potassium analogue, 86rubidium (86Rb+). 2 Exposure of the cells to calcium induced a time......- and concentration-dependent decrease in the ouabain-sensitive K+(86Rb+)-uptake of the cells without influencing the ouabain-resistant uptake. The development of the inhibition required the presence of potassium in the medium in the millimolar range (1.5-8.0 mM), and it did not occur at a concentration of potassium...

Effects of Potassium Sulfate [K2SO4] on The Element Contents, Polyphenol Content, Antioxidant and Antimicrobial Activities of Milk Thistle [Silybum Marianum].

Science.gov (United States)

Yaldiz, Gulsum

2017-01-01

Silybum marianum L. (Milk thistle) is native to the Mediterranean basin and is now widespread throughout the world. It's sprout is used as a herbal medicine for the treatment of liver disease for centuries. The seeds of milk thistle contain silymarin, an isomeric mixture of flavonolignans [silybin, silychristin, and silydianin]. Silymarin acts as a strong anti-hepatotoxic. The objective of this study was to evaluate the influences of potassium sulfate [K 2 SO 4 ] fertilizer doses on polyphenol content, some nutrient elements, antioxidant and antimicrobial activities of milk thistle at experimental fields of Ordu University in Turkey. The antimicrobial activities of seed ethanol extracts and seed oil were tested in vitro against Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli, (E. coli) Staphylococcus aureus (S. aureus), Aspergillus niger (A. niger) and Candida albicans (C. albicans) using the disc diffusion method. Free radical scavenging activity of the ethanolic extracts of milk thistle was determined spectrophotometrically by monitoring the disappearance of 2, 2-diphenyl-1-picrylhydrazil (DPPH•) at 517 nm according to the method described by Brand-Williams et al .[17] The phenolic contents in the ethanolic extracts of milk thistle were determined according to the procedure described by Slinkard and Singleton[19] with a slight modification of using a Folin-Ciocalteu phenolic reagent. The amount of total flavonoid in the ethanolic extracts was measured by aluminum chloride [AlCl 3 ] colorimetric assay. The ions in aerosol samples were determined by using Dionex ICS 1100 Series ion chromatography. Seed and seed oils obtained from obvious doses of potassium sulfate [0, 30, 60, 90 and 120 kg ha -1 fertilizer applications showed antimicrobial activities against E. coli , A. niger and P. aeruginosa . The application of 90 kg ha -1 of K 2 SO 4 on seed oil resulted in the highest antimicrobial activities. At 100 µg mL -1 and 200 µg mL -1 , except the highest

Time-dependent friction and solvation time correlation function

International Nuclear Information System (INIS)

Samanta, Alok; Ali, Sk Musharaf; Ghosh, Swapan K

2005-01-01

We have derived a new relation between the time-dependent friction and solvation time correlation function (STCF) for non-polar fluids. The friction values calculated using this relation and simulation results on STCF for a Lennard-Jones fluid are shown to have excellent agreement with the same obtained through mode-coupling theory. Also derived is a relation between the time-dependent dielectric friction and STCF for polar fluids. Routes are thus provided to obtain the time-dependent friction (non-polar as well as dielectric) from an experimentally measured quantity like STCF, even if the interparticle interaction potential is not known

Potassium in milk and milk products

International Nuclear Information System (INIS)

Sombrito, E.Z.; Nuguid, Z.F.S.; Tangonan, M.C.

1989-01-01

The amount of potassium in imported processed milk was determined by gamma spectral analysis. The results show that the potassium content of diluted infant formula milk is closest to the reported mean concentration of potassium in human milk while other milk types have potassium values similar to the potassium content of cow milk. (Auth.). 2 figs., 5 refs

Potassium effects on kinetics of propane oxydehydrogenation on vanadia-titania catalyst

International Nuclear Information System (INIS)

Grabowski, R.; Samson, K.

2003-01-01

Oxidative dehydrogenation of propane (ODH) over V 2 O 5 /TiO 2 and V 2 O 5 /TiO 2 doped with K was carried out by measuring conversions and selectiveness for various feed compositions, contact times and temperatures. The results obtained for both catalysts were interpreted on the basis of the mechanism, in which propene is formed through Eley-Rideal sequence of steps, i.e. without participation of the adsorbed propane species. Kinetic constants (activation energies, pre-exponential factors) for the model of ODH reaction of propane on these catalysts, obtained on the basis of steady-state results, are given. Addition of K to vanadia-titania catalysts leads to decrease of total combustion of propane and consecutive combustion of propene. It has been found that the direct propane total oxidation is 5 - 9 times lower than that of the consecutive propene oxidation and is almost temperature independent for potassium doped catalyst, whereas it quickly decreases with temperature for a non-doped catalyst. Secondly, the addition of K to a vanadia-titania catalyst decreases the activation energies for propene formation (k 1 ), parallel formation of CO x (k 3 ) and reoxidation of the catalyst (k os ). Potassium exhibits a stronger inhibitory effect on the secondary propene combustion, what reflects the lower activity of V 5+ cations modified by the strongly basic alkali oxide species. (author)

Time Dependent Quantum Mechanics

OpenAIRE

Morrison, Peter G.

2012-01-01

We present a systematic method for dealing with time dependent quantum dynamics, based on the quantum brachistochrone and matrix mechanics. We derive the explicit time dependence of the Hamiltonian operator for a number of constrained finite systems from this formalism. Once this has been achieved we go on to calculate the wavevector as a function of time, in order to demonstrate the use of matrix methods with respect to several concrete examples. Interesting results are derived for elliptic ...

Noisy time-dependent spectra

International Nuclear Information System (INIS)

Shore, B.W.; Eberly, J.H.

1983-01-01

The definition of a time-dependent spectrum registered by an idealized spectrometer responding to a time-varying electromagnetic field as proposed by Eberly and Wodkiewicz and subsequently applied to the spectrum of laser-induced fluorescence by Eberly, Kunasz, and Wodkiewicz is here extended to allow a stochastically fluctuating (interruption model) environment: we provide an algorithm for numerical determination of the time-dependent fluorescence spectrum of an atom subject to excitation by an intense noisy laser and interruptive relaxation

MiRNA-135a regulates the expression of small conductance calcium-activated potassium (SK3) channels in epilepsy-like conditions

NARCIS (Netherlands)

Honrath, Birgit; Norwood, Braxton; Tanrioever, Gaye; Kuter, Katarzyna; Henshall, David C; Aksel-Aksoy, Ayla; Schratt, Gerhard; Pasterkamp, Jeroen; Dencher, Norbert A.; Nieweg, Katja; Culmsee, Carsten; Dolga, Amalia Mihalea

2017-01-01

Background Excessive and hypersynchronous neuronal discharges are key characteristics in the pathophysiology of neurological disorders such as epilepsy. Owing to their ability of regulating neuronal excitability, small conductance calcium-activated potassium (SK) channels have been implicated in

Textural and chemical characterizations of adsorbent prepared from palm shell by potassium hydroxide impregnation at different stages.

Science.gov (United States)

Guo, Jia; Lua, Aik Chong

2002-10-15