Dorsal–Ventral Gradient for Neuronal Plasticity in the Embryonic Spinal Cord

PubMed Central

Pineda, Ricardo H.; Ribera, Angeles B.

2008-01-01

Within the developing Xenopus spinal cord, voltage-gated potassium (Kv) channel genes display different expression patterns, many of which occur in opposing dorsal–ventral gradients. Regional differences in Kv gene expression would predict different patterns of potassium current (IKv) regulation. However, during the first 24 h of postmitotic differentiation, all primary spinal neurons undergo a temporally coordinated upregulation of IKv density that shortens the duration of the action potential. Here, we tested whether spinal neurons demonstrate regional differences in IKv regulation subsequent to action potential maturation. We show that two types of neurons, I and II, can be identified in culture on the basis of biophysical and pharmacological properties of IKv and different firing patterns. Chronic increases in extracellular potassium, a signature of high neuronal activity, do not alter excitability properties of either neuron type. However, elevating extracellular potassium acutely after the period of action potential maturation leads to different changes in membrane properties of the two types of neurons. IKv of type I neurons gains sensitivity to the blocker XE991, whereas type II neurons increase IKv density and fire fewer action potentials. Moreover, by recording from neurons in vivo, we found that primary spinal neurons can be identified as either type I or type II. Type I neurons predominate in dorsal regions, whereas type II neurons localize to ventral regions. The findings reveal a dorsal–ventral gradient for IKv regulation and a novel form of neuronal plasticity in spinal cord neurons. PMID:18385340

Role of A-type potassium currents in excitability, network synchronicity and epilepsy

PubMed Central

Fransén, Erik; Tigerholm, Jenny

2011-01-01

A range of ionic currents have been suggested to be involved in distinct aspects of epileptogenesis. Based on pharmacological and genetic studies, potassium currents have been implicated, in particular the transient A-type potassium current (KA). Epileptogenic activity comprises a rich repertoire of characteristics, one of which is synchronized activity of principal cells as revealed by occurrences of for instance fast ripples. Synchronized activity of this kind is particularly efficient in driving target cells into spiking. In the recipient cell, this synchronized input generates large brief compound EPSPs. The fast activation and inactivation of KA lead us to hypothesize a potential role in suppression of such EPSPs. In this work, using computational modeling, we have studied the activation of KA by synaptic inputs of different levels of synchronicity. We find that KA participates particularly in suppressing inputs of high synchronicity. We also show that the selective suppression stems from the current's ability to become activated by potentials with high slopes. We further show that KA suppresses input mimicing the activity of a fast ripple. Finally, we show that the degree of selectivity of KA can be modified by changes to its kinetic parameters, changes of the type that are produced by the modulatory action of KChIPs and DPPs. We suggest that the wealth of modulators affecting KA might be explained by a need to control cellular excitability in general and suppression of responses to synchronicity in particular. We also suggest that compounds changing KA-kinetics may be used to pharmacologically improve epileptic status. PMID:19777555

Down-regulation of A-type potassium channel in gastric-specific DRG neurons in a rat model of functional dyspepsia.

PubMed

Li, S; Chen, J D Z

2014-07-01

Although without evidence of organic structural abnormalities, pain or discomfort is a prominent symptom of functional dyspepsia and considered to reflect visceral hypersensitivity whose underlying mechanism is poorly understood. Here, we studied electrophysiological properties and expression of voltage-gated potassium channels in dorsal root ganglion (DRG) neurons in a rat model of functional dyspepsia induced by neonatal gastric irritation. Male Sprague-Dawley rat pups at 10-day old received 0.1% iodoacetamide (IA) or vehicle by oral gavage for 6 days and studied at adulthood. Retrograde tracer-labeled gastric-specific T8 -T12 DRG neurons were harvested for the patch-clamp study in voltage and current-clamp modes and protein expression of K(+) channel in T8 -T12 DRGs was examined by western blotting. (1) Gastric specific but not non-gastric DRG neurons showed an enhanced excitability in neonatal IA-treated rats compared to the control: depolarized resting membrane potentials, a lower current threshold for action potential (AP) activation, and an increase in the number of APs in response to current stimulation. (2) The current density of tetraethylammonium insensitive (transiently inactivating A-type current), but not the tetraethylammonium sensitive (slow-inactivating delayed rectifier K(+) currents), was significantly smaller in IA-treated rats (65.4 ± 6.9 pA/pF), compared to that of control (93.1 ± 8.3 pA/pF). (3) Protein expression of KV 4.3 was down-regulated in IA-treated rats. A-type potassium channels are significantly down-regulated in the gastric-specific DRG neurons in adult rats with mild neonatal gastric irritation, which in part contribute to the enhanced DRG neuron excitabilities that leads to the development of gastric hypersensitivity. © 2014 John Wiley & Sons Ltd.

Prolonged action potential duration in cardiac ablation of PDK1 mice.

PubMed

Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

2015-01-01

The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

Analysis of the Effects of Calcium or Magnesium on Voltage-Clamp Currents in Perfused Squid Axons Bathed in Solutions of High Potassium

PubMed Central

Rojas, Eduardo; Taylor, Robert E.; Atwater, Illani; Bezanilla, Francisco

1969-01-01

Isolated axons from the squid, Dosidicus gigas, were internally perfused with potassium fluoride solutions. Membrane currents were measured following step changes of membrane potential in a voltage-clamp arrangement with external isosmotic solution changes in the order: potassium-free artificial seawater; potassium chloride; potassium chloride containing 10, 25, 40 or 50, mM calcium or magnesium; and potassium-free artificial seawater. The following results suggest that the currents measured under voltage clamp with potassium outside and inside can be separated into two components and that one of them, the predominant one, is carried through the potassium system. (a) Outward currents in isosmotic potassium were strongly and reversibly reduced by tetraethylammonium chloride. (b) Without calcium or magnesium a progressive increase in the nontime-dependent component of the currents (leakage) occurred. (c) The restoration of calcium or magnesium within 15–30 min decreases this leakage. (d) With 50 mM divalent ions the steady-state current-voltage curve was nonlinear with negative resistance as observed in intact axons in isosmotic potassium. (e) The time-dependent components of the membrane currents were not clearly affected by calcium or magnesium. These results show a strong dependence of the leakage currents on external calcium or magnesium concentration but provide no support for the involvement of calcium or magnesium in the kinetics of the potassium system. PMID:5823216

Analysis of the effects of calcium or magnesium on voltage-clamp currents in perfused squid axons bathed in solutions of high potassium.

PubMed

Rojas, E; Taylor, R E; Atwater, I; Bezanilla, F

1969-10-01

Isolated axons from the squid, Dosidicus gigas, were internally perfused with potassium fluoride solutions. Membrane currents were measured following step changes of membrane potential in a voltage-clamp arrangement with external isosmotic solution changes in the order: potassium-free artificial seawater; potassium chloride; potassium chloride containing 10, 25, 40 or 50, mM calcium or magnesium; and potassium-free artificial seawater. The following results suggest that the currents measured under voltage clamp with potassium outside and inside can be separated into two components and that one of them, the predominant one, is carried through the potassium system. (a) Outward currents in isosmotic potassium were strongly and reversibly reduced by tetraethylammonium chloride. (b) Without calcium or magnesium a progressive increase in the nontime-dependent component of the currents (leakage) occurred. (c) The restoration of calcium or magnesium within 15-30 min decreases this leakage. (d) With 50 mM divalent ions the steady-state current-voltage curve was nonlinear with negative resistance as observed in intact axons in isosmotic potassium. (e) The time-dependent components of the membrane currents were not clearly affected by calcium or magnesium. These results show a strong dependence of the leakage currents on external calcium or magnesium concentration but provide no support for the involvement of calcium or magnesium in the kinetics of the potassium system.

Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons

PubMed Central

Kimm, Tilia; Khaliq, Zayd M.

2015-01-01

Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency–current (f–I) relationship, whereas BK channel inhibition had little effect on the f–I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f–I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. SIGNIFICANCE STATEMENT This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both channel types participate in action potential repolarization about equally, they have contrasting and partially opposite effects in regulating neuronal firing at frequencies typical of bursting. Our analysis shows that this results from their different kinetic properties, with fast-activating BK channels serving to short-circuit activation of Kv2 channels, which tend to slow firing by producing a deep afterhyperpolarization. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. PMID:26674866

Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons.

PubMed

Kimm, Tilia; Khaliq, Zayd M; Bean, Bruce P

2015-12-16

Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both channel types participate in action potential repolarization about equally, they have contrasting and partially opposite effects in regulating neuronal firing at frequencies typical of bursting. Our analysis shows that this results from their different kinetic properties, with fast-activating BK channels serving to short-circuit activation of Kv2 channels, which tend to slow firing by producing a deep afterhyperpolarization. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. Copyright © 2015 the authors 0270-6474/15/3516404-14$15.00/0.

Calcium Currents of Olfactory Bulb Juxtaglomerular Cells: Profile and Multiple Conductance Plateau Potential Simulation

PubMed Central

Masurkar, Arjun V.; Chen, Wei R.

2011-01-01

The olfactory glomerulus is the locus of information transfer between olfactory sensory neurons and output neurons of the olfactory bulb. Juxtaglomerular cells (JGCs) may influence intraglomerular processing by firing plateau potentials that support multiple spikes. It is unclear what inward currents mediate this firing pattern. In previous work, we characterized potassium currents of JGCs. We focus here on the inward currents using whole cell current clamp and voltage recording in a rat in vitro slice preparation, as well as computer simulation. We first showed that sodium current was not required to mediate plateau potentials. Voltage clamp characterization of calcium current (ICa) determined that ICa consisted of a slow activating, rapidly inactivating (τ10%–90% rise 6–8ms, τinactivation 38–77ms) component Icat1, similar to T-type currents, and a sustained (τinactivation≫500ms) component Icat2, likely composed of L-type and P/Q-type currents. We used computer simulation to test their roles in plateau potential firing. We robustly modeled Icat1 and Icat2 to Hodgkin-Huxley schemes (m3h and m2, respectively) and simulated a JGC plateau potential with 6 conductances: calcium currents as above, potassium currents from our prior study (A-type Ikt1, D-type Ikt2, delayed rectifier Ikt3), and a fast sodium current (INa). We demonstrated that Icat1 was required for mediating the plateau potential, unlike INa and Icat2, and its τinactivation determined plateau duration. We also found that Ikt1 dictated plateau potential shape more than Ikt2 and Ikt3. The influence of these two transient and opposing conductances suggests a unique mechanism of plateau potential physiology. PMID:21704681

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons

PubMed Central

Guan, Dongxu; Horton, Leslie R.; Armstrong, William E.

2011-01-01

Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K+ channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K+ currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex. Both the persistent/slowly inactivating and transient components of the total K+ current increased in density with postnatal age. We used specific pharmacological agents to test the relative contributions of putative Kv1- and Kv2-mediated currents (100 nM α-dendrotoxin and 600 nM stromatoxin, respectively). A combination of voltage protocol, pharmacology, and curve fitting was used to isolate the rapidly inactivating A-type current. We found that the density of all identified current components increased with postnatal age, approaching a plateau at 3–5 wk. We found no significant changes in the relative proportions or kinetics of any component between postnatal weeks 1 and 5, except that the activation time constant for A-type current was longer at 1 wk. The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4–5 wk of age. PMID:21451062

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons.

PubMed

Guan, Dongxu; Horton, Leslie R; Armstrong, William E; Foehring, Robert C

2011-06-01

Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K(+) channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K(+) currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex. Both the persistent/slowly inactivating and transient components of the total K(+) current increased in density with postnatal age. We used specific pharmacological agents to test the relative contributions of putative Kv1- and Kv2-mediated currents (100 nM α-dendrotoxin and 600 nM stromatoxin, respectively). A combination of voltage protocol, pharmacology, and curve fitting was used to isolate the rapidly inactivating A-type current. We found that the density of all identified current components increased with postnatal age, approaching a plateau at 3-5 wk. We found no significant changes in the relative proportions or kinetics of any component between postnatal weeks 1 and 5, except that the activation time constant for A-type current was longer at 1 wk. The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4-5 wk of age.

Multi-walled carbon nanotubes suppress potassium channel activities in PC12 cells

NASA Astrophysics Data System (ADS)

Xu, Haifei; Bai, Juan; Meng, Jie; Hao, Wei; Xu, Haiyan; Cao, Ji-Min

2009-07-01

The advancement in nanotechnology has produced technological and conceptual breakthroughs but the effects nanomaterials have on organisms at the cellular level are poorly understood. Here we report that carboxyl-terminated multi-walled carbon nanotubes (MWCNTs) act as antagonists of three types of potassium channels as assessed by whole-cell patch clamp electrophysiology on undifferentiated pheochromocytoma (PC12) cells. Our results showed that carboxyl-terminated MWCNTs suppress the current densities of Ito, IK and IK1 in a time-dependent and irreversible manner. The suppressions were most distinct 24 h after incubation with MWCNTs. However, MWCNTs did not significantly change the expression levels of reactive oxygen species (ROS) or intracellular free calcium and also did not alter the mitochondrial membrane potential (ΔΨm) in PC12 cells. These results suggest that oxidative stress was not involved in the MWCNTs suppression of Ito, IK and IK1 current densities. Nonetheless, the suppression of potassium currents by MWCNTs will impact on electrical signaling of excitable cells such as neurons and muscles.

Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current

PubMed Central

Liu, Pin W.; Blair, Nathaniel T.

2017-01-01

Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC50 <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons. SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. PMID:28877968

Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.

PubMed

Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P

2017-10-04

Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons. SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. Copyright © 2017 the authors 0270-6474/17/379705-10$15.00/0.

Effect of urinary trypsin inhibitor on potassium currents: fetus modulates membrane excitability by production of UTI.

PubMed

Takeuchi, Kinya; Fukuda, Atsuo; Kanayama, Naohiro

2004-01-01

Amniotic fluid contains a significant level of urinary trypsin inhibitor (UTI). Previously, we reported that UTI inhibits calcium influx of myometrium and it is effective in preventing uterine contraction. This study examined the effects of UTI upon potassium channels, which is important for membrane excitability. Whole-cell patch-clamp recordings were performed in fibroblasts derived from human fetal skin. Potassium currents were recorded and the effects of exogenous UTI and/or cadmium determined. Tetraethylammonium sensitive potassium currents were elicited by step or ramp stimulations at depolarized membrane potentials (over +30 mV). Administration of 1 micro M UTI significantly increased these potassium currents by 16.9%. When calcium channels were blocked by the administration of cadmium, UTI increased the rest of the potassium currents by 4.8%. This indicates that UTI increased calcium-dependent potassium currents by 94.8% but only increased voltage-dependent potassium currents by 4.8%. Urinary trypsin inhibitor is a physiological substance of fetal origin that modulates calcium-dependent and voltage-dependent potassium channels. These data suggest that UTI is capable of regulating the membrane properties of the fetal and myometrial cells in contact with amniotic fluid.

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

PubMed

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.

Voltage gated potassium channel antibodies positive autoimmune encephalopathy in a child: A case report and literature review of an under-recognized condition

PubMed Central

Ganesan, Subramanian; Beri, Sushil; Khan, Beri; Hussain, Nahin

2013-01-01

Autoimmune limbic encephalitis (LE) associated with voltage gated potassium channel antibodies (VGKC-Abs) in children is more common than previously thought and is not always paraneoplastic. Non-neoplastic, autoimmune LE associated with VGKC-Abs has been described recently. However, only few case reports in children as the disease is predominantly described in the adult population. It is likely that this type of autoimmune encephalitis is currently under-diagnosed and hence, under-treated, especially in children. We present a 13-year-old previously fit and healthy African girl diagnosed with LE and we reviewed the literature for its current management. PMID:24339586

KCNJ11: Genetic Polymorphisms and Risk of Diabetes Mellitus

PubMed Central

Mohamed, Zahurin; Abdullah, Nor Azizan; Haghvirdizadeh, Pantea; Haerian, Monir Sadat

2015-01-01

Diabetes mellitus (DM) is a major worldwide health problem and its prevalence has been rapidly increasing in the last century. It is caused by defects in insulin secretion or insulin action or both, leading to hyperglycemia. Of the various types of DM, type 2 occurs most frequently. Multiple genes and their interactions are involved in the insulin secretion pathway. Insulin secretion is mediated through the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. This channel is a heteromeric protein, composed of four inward-rectifier potassium ion channel (Kir6.2) tetramers, which form the pore of the KATP channel, as well as sulfonylurea receptor 1 subunits surrounding the pore. Kir6.2 is encoded by the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene, a member of the potassium channel genes. Numerous studies have reported the involvement of single nucleotide polymorphisms of the KCNJ11 gene and their interactions in the susceptibility to DM. This review discusses the current evidence for the contribution of common KCNJ11 genetic variants to the development of DM. Future studies should concentrate on understanding the exact role played by these risk variants in the development of DM. PMID:26448950

Calcium-Activated Potassium Channels at Nodes of Ranvier Secure Axonal Spike Propagation

PubMed Central

Gründemann, Jan; Clark, Beverley A.

2015-01-01

Summary Functional connectivity between brain regions relies on long-range signaling by myelinated axons. This is secured by saltatory action potential propagation that depends fundamentally on sodium channel availability at nodes of Ranvier. Although various potassium channel types have been anatomically localized to myelinated axons in the brain, direct evidence for their functional recruitment in maintaining node excitability is scarce. Cerebellar Purkinje cells provide continuous input to their targets in the cerebellar nuclei, reliably transmitting axonal spikes over a wide range of rates, requiring a constantly available pool of nodal sodium channels. We show that the recruitment of calcium-activated potassium channels (IK, KCa3.1) by local, activity-dependent calcium (Ca2+) influx at nodes of Ranvier via a T-type voltage-gated Ca2+ current provides a powerful mechanism that likely opposes depolarizing block at the nodes and is thus pivotal to securing continuous axonal spike propagation in spontaneously firing Purkinje cells. PMID:26344775

Distribution of the messenger RNA for the small conductance calcium-activated potassium channel SK3 in the adult rat brain and correlation with immunoreactivity.

PubMed

Tacconi, S; Carletti, R; Bunnemann, B; Plumpton, C; Merlo Pich, E; Terstappen, G C

2001-01-01

Small conductance calcium-activated potassium channels are voltage independent potassium channels which modulate the firing patterns of neurons by activating the slow component of the afterhyperpolarization. The genes encoding a family of small conductance calcium-activated potassium channels have been cloned and up to now three known members have been described and named small conductance calcium-activated potassium channel type 1, small conductance calcium-activated potassium channel type 2 and small conductance calcium-activated potassium channel type 3; the distribution of their messenger RNA in the rat CNS has already been performed but only in a limited detail. The present study represents the first detailed analysis of small conductance calcium-activated potassium channel type 3 mRNA distribution in the adult rat brain and resulted in a strong to moderate expression of signal in medial habenular nucleus, substantia nigra compact part, suprachiasmatic nucleus, ventral tegmental area, lateral septum, dorsal raphe and locus coeruleus. Immunohistological experiments were also performed and confirmed the presence of small conductance calcium-activated potassium channel type 3 protein in medial habenular nucleus, locus coeruleus and dorsal raphe. Given the importance of dorsal raphe, locus coeruleus and substantia nigra/ventral tegmental area for serotonergic, noradrenergic and dopaminergic transmission respectively, our results pose the morphological basis for further studies on the action of small conductance calcium-activated potassium channel type 3 in serotonergic, noradrenergic and dopaminergic transmission.

Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

PubMed Central

Wu, Delin; Jiang, Linqing; Wu, Hongjin; Wang, Shengqi; Zheng, Sidao; Yang, Jiyuan; Liu, Yuna; Ren, Jianxun; Chen, Xianbing

2013-01-01

Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (I K), the rapidly activating (I Kr) and slowly activating (I Ks) components of I K, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record I K (I Kr, I Ks) and the HERG K+ current. Results. GA (1, 5, and 10 μM) inhibited I K (I Kr, I Ks) and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of I K (I Kr, I Ks) and HERG K+ channel. PMID:24069049

β1-Adrenoceptor autoantibodies affect action potential duration and delayed rectifier potassium currents in guinea pigs.

PubMed

Zhao, Yuhui; Huang, Haixia; Du, Yunhui; Li, Xiao; Lv, Tingting; Zhang, Suli; Wei, Hua; Shang, Jianyu; Liu, Ping; Liu, Huirong

2015-01-01

β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (I K) plays a crucial role in APD, but the effects of β1-AAs on I K have not been completely illuminated. This work aimed to observe the effects of β1-AAs on I K and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and I K were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (I Kr), but similarly decreased the slowly activating delayed rectifier potassium current (I Ks) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients.

Equatorial potassium currents in lenses.

PubMed

Wind, B E; Walsh, S; Patterson, J W

1988-02-01

Earlier work with the vibrating probe demonstrated the existence of outward potassium currents at the equator and inward sodium currents at the optical poles of the lens. By adding microelectrodes to the system, it is possible to relate steady currents (J) to the potential difference (PD) measured with a microelectrode. By injecting an outward current (I), it is possible to determine resistances and also the PD at which the steady outward potassium current becomes zero (PDJ = 0). At this PD the concentration gradient for potassium efflux and the electrical gradient for potassium influx are balanced so that there is no net flow of potassium across the membranes associated with the production of J. The PDJ = 0 for 18 rat lenses was 86 mV and that for 12 frogs lenses was -95 mV. This agrees with the potassium equilibrium potential and provides strong evidence to support the view that the outward equatorial current, J, is a potassium current. With the injection of outward current, I, the PD becomes more negative, the outward equatorial current, J, decreases, and the inward current at the optical poles increases. This suggests that there are separate electrical loops for K+ and Na+ that are partially linked by the Na, K-pump. Using Ohm's law, it is possible to calculate the input resistance (R = delta PD/I), the resistance related to the production of J (RJ = delta PD/delta J), and the effect of the combined resistances (delta J/I). The driving force for J can be estimated (PDJ = 0-PD). The relationships among currents, voltages and resistance can be used to determine the characteristics of the membranes that are associated with the outward potassium current observed at the equator. The effects of graded deformation of the lens were determined. The effects were reversible. The sites of inward and outward currents were not altered. Following deformation, the equatorial current, J, increased, and the PD became less negative. The PDJ = 0 remains the same so the ratio of K+ concentrations across the membrane responsible for J is unchanged. Therefore, the decrease in PD is ascribed to an increase in Na+ permeance with a resultant increase in driving force accounting for the increase in J.

A biophysical model examining the role of low-voltage-activated potassium currents in shaping the responses of vestibular ganglion neurons.

PubMed

Hight, Ariel E; Kalluri, Radha

2016-08-01

The vestibular nerve is characterized by two broad groups of neurons that differ in the timing of their interspike intervals; some fire at highly regular intervals, whereas others fire at highly irregular intervals. Heterogeneity in ion channel properties has been proposed as shaping these firing patterns (Highstein SM, Politoff AL. Brain Res 150: 182-187, 1978; Smith CE, Goldberg JM. Biol Cybern 54: 41-51, 1986). Kalluri et al. (J Neurophysiol 104: 2034-2051, 2010) proposed that regularity is controlled by the density of low-voltage-activated potassium currents (IKL). To examine the impact of IKL on spike timing regularity, we implemented a single-compartment model with three conductances known to be present in the vestibular ganglion: transient sodium (gNa), low-voltage-activated potassium (gKL), and high-voltage-activated potassium (gKH). Consistent with in vitro observations, removing gKL depolarized resting potential, increased input resistance and membrane time constant, and converted current step-evoked firing patterns from transient (1 spike at current onset) to sustained (many spikes). Modeled neurons were driven with a time-varying synaptic conductance that captured the random arrival times and amplitudes of glutamate-driven synaptic events. In the presence of gKL, spiking occurred only in response to large events with fast onsets. Models without gKL exhibited greater integration by responding to the superposition of rapidly arriving events. Three synaptic conductance were modeled, each with different kinetics to represent a variety of different synaptic processes. In response to all three types of synaptic conductance, models containing gKL produced spike trains with irregular interspike intervals. Only models lacking gKL when driven by rapidly arriving small excitatory postsynaptic currents were capable of generating regular spiking. Copyright © 2016 the American Physiological Society.

Extracellular matrix of collagen modulates arrhythmogenic activity of pulmonary veins through p38 MAPK activation.

PubMed

Lu, Yen-Yu; Chen, Yao-Chang; Kao, Yu-Hsun; Chen, Shih-Ann; Chen, Yi-Jen

2013-06-01

Atrial fibrillation (AF) is the most common sustained arrhythmia. Cardiac fibrosis with enhanced extracellular collagen plays a critical role in the pathophysiology of AF through structural and electrical remodeling. Pulmonary veins (PVs) are important foci for AF genesis. The purpose of this study was to evaluate whether collagen can directly modulate PV arrhythmogenesis. Action potentials and ionic currents were investigated in isolated male New Zealand rabbit PV cardiomyocytes with and without collagen incubation (10μg/ml, 5-7h) using the whole-cell patch-clamp technique. Compared to control PV cardiomyocytes (n=25), collagen-treated PV cardiomyocytes (n=22) had a faster beating rate (3.2±04 vs. 1.9±0.2Hz, p<0.005) and a larger amplitude of delayed afterdepolarization (16±2 vs. 10±1mV, p<0.01). Moreover, collagen-treated PV cardiomyocytes showed a larger transient outward potassium current, small-conductance Ca(2+)-activated K(+) current, inward rectifier potassium current, pacemaker current, and late sodium current than control PV cardiomyocytes, but amplitudes of the sodium current, sustained outward potassium current, and L-type calcium current were similar. Collagen increased the p38 MAPK phosphorylation in PV cardiomyocytes as compared to control. The change of the spontaneous activity and action potential morphology were ameliorated by SB203580 (the p38 MAPK catalytic activity inhibitor), indicating that collagen can directly increase PV cardiomyocyte arrhythmogenesis through p38 MAPK activation, which may contribute to the pathogenesis of AF. Copyright © 2013 Elsevier Ltd. All rights reserved.

The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons

PubMed Central

Zagha, Edward; Mato, German; Rudy, Bernardo; Nadal, Marcela S.

2014-01-01

The signaling properties of thalamocortical (TC) neurons depend on the diversity of ion conductance mechanisms that underlie their rich membrane behavior at subthreshold potentials. Using patch-clamp recordings of TC neurons in brain slices from mice and a realistic conductance-based computational model, we characterized seven subthreshold ion currents of TC neurons and quantified their individual contributions to the total steady-state conductance at levels below tonic firing threshold. We then used the TC neuron model to show that the resting membrane potential results from the interplay of several inward and outward currents over a background provided by the potassium and sodium leak currents. The steady-state conductances of depolarizing Ih (hyperpolarization-activated cationic current), IT (low-threshold calcium current), and INaP (persistent sodium current) move the membrane potential away from the reversal potential of the leak conductances. This depolarization is counteracted in turn by the hyperpolarizing steady-state current of IA (fast transient A-type potassium current) and IKir (inwardly rectifying potassium current). Using the computational model, we have shown that single parameter variations compatible with physiological or pathological modulation promote burst firing periodicity. The balance between three amplifying variables (activation of IT, activation of INaP, and activation of IKir) and three recovering variables (inactivation of IT, activation of IA, and activation of Ih) determines the propensity, or lack thereof, of repetitive burst firing of TC neurons. We also have determined the specific roles that each of these variables have during the intrinsic oscillation. PMID:24760784

Nongenomic Glucocorticoid Suppression of a Postsynaptic Potassium Current via Emergent Autocrine Endocannabinoid Signaling in Hypothalamic Neuroendocrine Cells following Chronic Dehydration

PubMed Central

Wu, Ning

2017-01-01

Glucocorticoids rapidly stimulate endocannabinoid synthesis and modulation of synaptic transmission in hypothalamic neuroendocrine cells via a nongenomic signaling mechanism. The endocannabinoid actions are synapse-constrained by astrocyte restriction of extracellular spatial domains. Exogenous cannabinoids have been shown to modulate postsynaptic potassium currents, including the A-type potassium current (IA), in different cell types. The activity of magnocellular neuroendocrine cells is shaped by a prominent IA. We tested for a rapid glucocorticoid modulation of the postsynaptic IK and IA in magnocellular neuroendocrine cells of the hypothalamic paraventricular nucleus (PVN) using whole-cell recordings in rat brain slices. Application of the synthetic glucocorticoid dexamethasone (Dex) had no rapid effect on the IK or IA amplitude, voltage dependence, or kinetics in magnocellular neurons in slices from untreated rats. In magnocellular neurons from salt-loaded rats, however, Dex application caused a rapid suppression of the IA and a depolarizing shift in IA voltage dependence. Exogenously applied endocannabinoids mimicked the rapid Dex modulation of the IA, and CB1 receptor antagonists and agonists blocked and occluded the Dex-induced changes in the IA, respectively, suggesting an endocannabinoid dependence of the rapid glucocorticoid effect. Preincubation of control slices in a gliotoxin resulted in the partial recapitulation of the glucocorticoid-induced rapid suppression of the IA. These findings demonstrate a glucocorticoid suppression of the postsynaptic IA in PVN magnocellular neurons via an autocrine endocannabinoid-dependent mechanism following chronic dehydration, and suggest a possible role for astrocytes in the control of the autocrine endocannabinoid actions. PMID:28966975

Enhanced Sensitivity to Hyperpolarizing Inhibition in Mesoaccumbal Relative to Nigrostriatal Dopamine Neuron Subpopulations

PubMed Central

2017-01-01

Midbrain dopamine neurons recorded in vivo pause their firing in response to reward omission and aversive stimuli. While the initiation of pauses typically involves synaptic or modulatory input, intrinsic membrane properties may also enhance or limit hyperpolarization, raising the question of how intrinsic conductances shape pauses in dopamine neurons. Using retrograde labeling and electrophysiological techniques combined with computational modeling, we examined the intrinsic conductances that shape pauses evoked by current injections and synaptic stimulation in subpopulations of dopamine neurons grouped according to their axonal projections to the nucleus accumbens or dorsal striatum in mice. Testing across a range of conditions and pulse durations, we found that mesoaccumbal and nigrostriatal neurons differ substantially in rebound properties with mesoaccumbal neurons displaying significantly longer delays to spiking following hyperpolarization. The underlying mechanism involves an inactivating potassium (IA) current with decay time constants of up to 225 ms, and small-amplitude hyperpolarization-activated currents (IH), characteristics that were most often observed in mesoaccumbal neurons. Pharmacological block of IA completely abolished rebound delays and, importantly, shortened synaptically evoked inhibitory pauses, thereby demonstrating the involvement of A-type potassium channels in prolonging pauses evoked by GABAergic inhibition. Therefore, these results show that mesoaccumbal and nigrostriatal neurons display differential responses to hyperpolarizing inhibitory stimuli that favors a higher sensitivity to inhibition in mesoaccumbal neurons. These findings may explain, in part, observations from in vivo experiments that ventral tegmental area neurons tend to exhibit longer aversive pauses relative to SNc neurons. SIGNIFICANCE STATEMENT Our study examines rebound, postburst, and synaptically evoked inhibitory pauses in subpopulations of midbrain dopamine neurons. We show that pauses in dopamine neuron firing, evoked by either stimulation of GABAergic inputs or hyperpolarizing current injections, are enhanced by a subclass of potassium conductances that are recruited at voltages below spike threshold. Importantly, A-type potassium currents recorded in mesoaccumbal neurons displayed substantially slower inactivation kinetics, which, combined with weaker expression of hyperpolarization-activated currents, lengthened hyperpolarization-induced delays in spiking relative to nigrostriatal neurons. These results suggest that input integration differs among dopamine neurons favoring higher sensitivity to inhibition in mesoaccumbal neurons and may partially explain in vivo observations that ventral tegmental area neurons exhibit longer aversive pauses relative to SNc neurons. PMID:28219982

Decreased inward rectifier potassium current IK1 in dystrophin-deficient ventricular cardiomyocytes.

PubMed

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

2017-03-04

Kir2.x channels in ventricular cardiomyocytes (most prominently Kir2.1) account for the inward rectifier potassium current I K1 , which controls the resting membrane potential and the final phase of action potential repolarization. Recently it was hypothesized that the dystrophin-associated protein complex (DAPC) is important in the regulation of Kir2.x channels. To test this hypothesis, we investigated potential I K1 abnormalities in dystrophin-deficient ventricular cardiomyocytes derived from the hearts of Duchenne muscular dystrophy mouse models. We found that I K1 was substantially diminished in dystrophin-deficient cardiomyocytes when compared to wild type myocytes. This finding represents the first functional evidence for a significant role of the DAPC in the regulation of Kir2.x channels.

Calcium-calmodulin-dependent kinase II modulates Kv4.2 channel expression and upregulates neuronal A-type potassium currents.

PubMed

Varga, Andrew W; Yuan, Li-Lian; Anderson, Anne E; Schrader, Laura A; Wu, Gang-Yi; Gatchel, Jennifer R; Johnston, Daniel; Sweatt, J David

2004-04-07

Calcium-calmodulin-dependent kinase II (CaMKII) has a long history of involvement in synaptic plasticity, yet little focus has been given to potassium channels as CaMKII targets despite their importance in repolarizing EPSPs and action potentials and regulating neuronal membrane excitability. We now show that Kv4.2 acts as a substrate for CaMKII in vitro and have identified CaMKII phosphorylation sites as Ser438 and Ser459. To test whether CaMKII phosphorylation of Kv4.2 affects channel biophysics, we expressed wild-type or mutant Kv4.2 and the K(+) channel interacting protein, KChIP3, with or without a constitutively active form of CaMKII in Xenopus oocytes and measured the voltage dependence of activation and inactivation in each of these conditions. CaMKII phosphorylation had no effect on channel biophysical properties. However, we found that levels of Kv4.2 protein are increased with CaMKII phosphorylation in transfected COS cells, an effect attributable to direct channel phosphorylation based on site-directed mutagenesis studies. We also obtained corroborating physiological data showing increased surface A-type channel expression as revealed by increases in peak K(+) current amplitudes with CaMKII phosphorylation. Furthermore, endogenous A-currents in hippocampal pyramidal neurons were increased in amplitude after introduction of constitutively active CaMKII, which results in a decrease in neuronal excitability in response to current injections. Thus CaMKII can directly modulate neuronal excitability by increasing cell-surface expression of A-type K(+) channels.

Characterization of ionic currents of cells of the subfornical organ that project to the supraoptic nuclei

NASA Technical Reports Server (NTRS)

Johnson, R. F.; Beltz, T. G.; Jurzak, M.; Wachtel, R. E.; Johnson, A. K.

1999-01-01

The subfornical organ (SFO) is a forebrain structure that converts peripheral blood-borne signals reflecting the hydrational state of the body to neural signals and then through efferent fibers conveys this information to several central nervous system structures. One of the forebrain areas receiving input from the SFO is the supraoptic nucleus (SON), a source of vasopressin synthesis and control of release from the posterior pituitary. Little is known of the transduction and transmission processes by which this conversion of systemic information to brain input occurs. As a step in elucidating these mechanisms, the present study characterized the ionic currents of dissociated cells of the SFO that were identified as neurons that send efferents to the SON. A retrograde tracer was injected into the SON area in eleven-day-old rats. After three days for retrograde transport of the label, the SFOs of these animals were dissociated and plated for tissue culture. The retrograde tracer was used to identify the soma of SFO cells projecting to the SON so that voltage-dependent ionic currents using whole-cell voltage clamp methods could be studied. The three types of currents in labeled SFO neurons were characterized as a 1) rapid, transient inward current that can be blocked by tetrodotoxin (TTX) characteristic of a sodium current; 2) slow-onset sustained outward current that can be blocked by tetraethylammonium (TEA) characteristic of a delayed rectifier potassium current; and 3) remaining outward current that has a rapid-onset and transient characteristic of a potassium A-type current. Copyright 1999 Elsevier Science B.V.

Topical 5% potassium permanganate solution accelerates the healing process in chronic diabetic foot ulcers.

PubMed

Delgado-Enciso, Iván; Madrigal-Perez, Violeta M; Lara-Esqueda, Agustin; Diaz-Sanchez, Martha G; Guzman-Esquivel, Jose; Rosas-Vizcaino, Luis E; Virgen-Jimenez, Oscar O; Kleiman-Trujillo, Juleny; Lagarda-Canales, Maria R; Ceja-Espiritu, Gabriel; Rangel-Salgado, Viridiana; Lopez-Lemus, Uriel A; Delgado-Enciso, Josuel; Lara-Basulto, Agustin D; Soriano Hernández, Alejandro D

2018-02-01

Potassium permanganate has been reported to be an effective treatment for certain types of wounds. The aim of the present study was to evaluate the use of potassium permanganate in the treatment of diabetic foot ulcers. A single-blind, randomized, controlled clinical trial was conducted on patients with type 2 diabetes mellitus that presented with a foot ulcer persisting for >3 months. The control group (n=10) was treated with the current standard treatment, which comprises of measures for reducing pressure in the ulcerated area, daily cleansing of the ulcer with potable water and antiseptic wash solution, and the application of a disinfectant solution on the entire surface area of the ulcer; while the intervention group (n=15) received the standard treatment plus 5% topical potassium permanganate solution applied once a day for 21 days. In the intervention group, 1 patient did not tolerate the treatment and was eliminated from the study on the first day. The remaining patients tolerated the interventions well. At the end of the treatment period, ulcers in the control group had decreased by 38% whereas those in the intervention group decreased by 73% (P<0.009). The degree of decrease was also investigated; the ulcer size was ≥50% decreased in 40% of patients in the control group and in 86% of patients in the intervention group (P=0.02). In conclusion, the results of the present study indicate that topical potassium permanganate is well tolerated and significantly accelerates the healing process of diabetic foot ulcers.

Topical 5% potassium permanganate solution accelerates the healing process in chronic diabetic foot ulcers

PubMed Central

Delgado-Enciso, Iván; Madrigal-Perez, Violeta M.; Lara-Esqueda, Agustin; Diaz-Sanchez, Martha G.; Guzman-Esquivel, Jose; Rosas-Vizcaino, Luis E.; Virgen-Jimenez, Oscar O.; Kleiman-Trujillo, Juleny; Lagarda-Canales, Maria R.; Ceja-Espiritu, Gabriel; Rangel-Salgado, Viridiana; Lopez-Lemus, Uriel A.; Delgado-Enciso, Josuel; Lara-Basulto, Agustin D.; Soriano Hernández, Alejandro D.

2018-01-01

Potassium permanganate has been reported to be an effective treatment for certain types of wounds. The aim of the present study was to evaluate the use of potassium permanganate in the treatment of diabetic foot ulcers. A single-blind, randomized, controlled clinical trial was conducted on patients with type 2 diabetes mellitus that presented with a foot ulcer persisting for >3 months. The control group (n=10) was treated with the current standard treatment, which comprises of measures for reducing pressure in the ulcerated area, daily cleansing of the ulcer with potable water and antiseptic wash solution, and the application of a disinfectant solution on the entire surface area of the ulcer; while the intervention group (n=15) received the standard treatment plus 5% topical potassium permanganate solution applied once a day for 21 days. In the intervention group, 1 patient did not tolerate the treatment and was eliminated from the study on the first day. The remaining patients tolerated the interventions well. At the end of the treatment period, ulcers in the control group had decreased by 38% whereas those in the intervention group decreased by 73% (P<0.009). The degree of decrease was also investigated; the ulcer size was ≥50% decreased in 40% of patients in the control group and in 86% of patients in the intervention group (P=0.02). In conclusion, the results of the present study indicate that topical potassium permanganate is well tolerated and significantly accelerates the healing process of diabetic foot ulcers. PMID:29435274

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

PubMed

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.

21 CFR 184.1622 - Potassium chloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium chloride. 184.1622 Section 184.1622 Food... Specific Substances Affirmed as GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg... levels not to exceed current good manufacturing practice. Potassium chloride may be used in infant...

21 CFR 184.1622 - Potassium chloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium chloride. 184.1622 Section 184.1622 Food... Specific Substances Affirmed as GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg... levels not to exceed current good manufacturing practice. Potassium chloride may be used in infant...

The Pure Rotational Spectrum of KO

NASA Astrophysics Data System (ADS)

Burton, Mark; Russ, Benjamin; Sheridan, Phillip M.; Bucchino, Matthew; Ziurys, Lucy M.

2017-06-01

The pure rotational spectrum of potassium monoxide (KO) has been recorded using millimeter-wave direct absorption spectroscopy. KO was synthesized by the reaction of potassium vapor, produced in a Broida-type oven, with nitrous oxide. No DC discharge was necessary. Eleven rotational transitions belonging to the ^{2}Π_{3/2} spin-orbit component have been measured and have been fit successfully to a case (c) Hamiltonian. Rotational and lambda-doubling constants for this spin-orbit component have been determined. It has been suggested that the ground electronic state of KO is either ^{2}Π (as for LiO and NaO) or ^{2}Σ (as for RbO and CsO), both of which lie close in energy. Recent computational studies favor a ^{2}Σ ground state. Further measurements of the rotational transitions of the ^{2}Π_{1/2} spin-orbit component and the ^{2}Σ state are currently in progress, as well as the potassium hyperfine structure.

Mineral of the month: potash

USGS Publications Warehouse

Searls, James P.

2005-01-01

In 1807, Sir Humphrey Davy discovered a metal during the electrolysis of potassium hydroxide; he named the metal potassium because it came from potash recovered from wood ashes. The four types of potash are the water-soluble compounds potassium chloride, potassium sulfate, potassium-magnesium sulfate and potassium nitrate. The early uses of potash were in glass and soap manufacturing, as a diuretic, and another form was used in gunpowder.

Dynamic, nonlinear feedback regulation of slow pacemaking by A-type potassium current in ventral tegmental area neurons.

PubMed

Khaliq, Zayd M; Bean, Bruce P

2008-10-22

We analyzed ionic currents that regulate pacemaking in dopaminergic neurons of the mouse ventral tegmental area by comparing voltage trajectories during spontaneous firing with ramp-evoked currents in voltage clamp. Most recordings were made in brain slice, with key experiments repeated using acutely dissociated neurons, which gave identical results. During spontaneous firing, net ionic current flowing between spikes was calculated from the time derivative of voltage multiplied by cell capacitance, signal-averaged over many firing cycles to enhance resolution. Net inward interspike current had a distinctive nonmonotonic shape, reaching a minimum (generally <1 pA) between -60 and -55 mV. Under voltage clamp, ramps over subthreshold voltages elicited a time- and voltage-dependent outward current that peaked near -55 mV. This current was undetectable with 5 mV/s ramps and increased steeply with depolarization rate over the range (10-50 mV/s) typical of natural pacemaking. Ramp-evoked subthreshold current was resistant to alpha-dendrotoxin, paxilline, apamin, and tetraethylammonium but sensitive to 4-aminopyridine and 0.5 mM Ba2+, consistent with A-type potassium current (I(A)). Same-cell comparison of currents elicited by various ramp speeds with natural spontaneous depolarization showed how the steep dependence of I(A) on depolarization rate results in small net inward currents during pacemaking. These results reveal a mechanism in which subthreshold I(A) is near zero at steady state, but is engaged at depolarization rates >10 mV/s to act as a powerful, supralinear feedback element. This feedback mechanism explains how net ionic current can be constrained to <1-2 pA but reliably inward, thus enabling slow, regular firing.

Biophysically realistic minimal model of dopamine neuron

NASA Astrophysics Data System (ADS)

Oprisan, Sorinel

2008-03-01

We proposed and studied a new biophysically relevant computational model of dopaminergic neurons. Midbrain dopamine neurons are involved in motivation and the control of movement, and have been implicated in various pathologies such as Parkinson's disease, schizophrenia, and drug abuse. The model we developed is a single-compartment Hodgkin-Huxley (HH)-type parallel conductance membrane model. The model captures the essential mechanisms underlying the slow oscillatory potentials and plateau potential oscillations. The main currents involved are: 1) a voltage-dependent fast calcium current, 2) a small conductance potassium current that is modulated by the cytosolic concentration of calcium, and 3) a slow voltage-activated potassium current. We developed multidimensional bifurcation diagrams and extracted the effective domains of sustained oscillations. The model includes a calcium balance due to the fundamental importance of calcium influx as proved by simultaneous electrophysiological and calcium imaging procedure. Although there are significant evidences to suggest a partially electrogenic calcium pump, all previous models considered only elecrtogenic pumps. We investigated the effect of the electrogenic calcium pump on the bifurcation diagram of the model and compared our findings against the experimental results.

Contribution of dairy products to dietary potassium intake in the United States population.

PubMed

McGill, Carla R; Fulgoni, Victor L; DiRienzo, Douglas; Huth, Peter J; Kurilich, Anne C; Miller, Gregory D

2008-02-01

Adequate dietary potassium intake is associated with a reduced risk of cardiovascular and other chronic diseases. The Dietary Guidelines for Americans 2005 identifies milk and milk products as a major contributor of dietary potassium and lists dairy products, along with fruits and vegetables, as food groups to encourage. This paper further examines the impact of dairy consumption on the potassium intake of the United States (US) population. Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 we determined potassium intakes for various age groups of individuals who met the recommended number of dairy servings compared to those who did not. We also examined the impact of dairy servings consumed on mean and median potassium intakes and compared intakes to the age-appropriate Adequate Intakes (AI). For all age groups, mean and median potassium intakes did not meet the respective AI. Mean potassium intakes were significantly greater in those subjects who met dairy intake recommendations compared to those who did not for all age groups. Mean and median potassium intakes increased with increasing dairy intake but were below current intake recommendations for all age groups analyzed. For adults age 19 to 50, 16.1% consumed the recommended number of dairy servings per day. For those 51 and older, 10.7% met current dairy intake recommendations. Consumption of dairy products is below current recommendations which contributes in part to suboptimal dietary potassium intakes among a large proportion of the US population. Since adequate potassium intake is associated with decreased risk of chronic disease, consumption of a variety of potassium-rich foods, including fruits, vegetables and low-fat and fat free dairy products, should continue to be encouraged.

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

PubMed

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.

Ion channels in plants.

PubMed

Hedrich, Rainer

2012-10-01

Since the first recordings of single potassium channel activities in the plasma membrane of guard cells more than 25 years ago, patch-clamp studies discovered a variety of ion channels in all cell types and plant species under inspection. Their properties differed in a cell type- and cell membrane-dependent manner. Guard cells, for which the existence of plant potassium channels was initially documented, advanced to a versatile model system for studying plant ion channel structure, function, and physiology. Interestingly, one of the first identified potassium-channel genes encoding the Shaker-type channel KAT1 was shown to be highly expressed in guard cells. KAT1-type channels from Arabidopsis thaliana and its homologs from other species were found to encode the K(+)-selective inward rectifiers that had already been recorded in early patch-clamp studies with guard cells. Within the genome era, additional Arabidopsis Shaker-type channels appeared. All nine members of the Arabidopsis Shaker family are localized at the plasma membrane, where they either operate as inward rectifiers, outward rectifiers, weak voltage-dependent channels, or electrically silent, but modulatory subunits. The vacuole membrane, in contrast, harbors a set of two-pore K(+) channels. Just very recently, two plant anion channel families of the SLAC/SLAH and ALMT/QUAC type were identified. SLAC1/SLAH3 and QUAC1 are expressed in guard cells and mediate Slow- and Rapid-type anion currents, respectively, that are involved in volume and turgor regulation. Anion channels in guard cells and other plant cells are key targets within often complex signaling networks. Here, the present knowledge is reviewed for the plant ion channel biology. Special emphasis is drawn to the molecular mechanisms of channel regulation, in the context of model systems and in the light of evolution.

BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells

PubMed Central

Gu, Ning; Vervaeke, Koen; Storm, Johan F

2007-01-01

Neuronal potassium (K+) channels are usually regarded as largely inhibitory, i.e. reducing excitability. Here we show that BK-type calcium-activated K+ channels enhance high-frequency firing and cause early spike frequency adaptation in neurons. By combining slice electrophysiology and computational modelling, we investigated functions of BK channels in regulation of high-frequency firing in rat CA1 pyramidal cells. Blockade of BK channels by iberiotoxin (IbTX) selectively reduced the initial discharge frequency in response to strong depolarizing current injections, thus reducing the early spike frequency adaptation. IbTX also blocked the fast afterhyperpolarization (fAHP), slowed spike rise and decay, and elevated the spike threshold. Simulations with a computational model of a CA1 pyramidal cell confirmed that the BK channel-mediated rapid spike repolarization and fAHP limits activation of slower K+ channels (in particular the delayed rectifier potassium current (IDR)) and Na+ channel inactivation, whereas M-, sAHP- or SK-channels seem not to be important for the early facilitating effect. Since the BK current rapidly inactivates, its facilitating effect diminishes during the initial discharge, thus producing early spike frequency adaptation by an unconventional mechanism. This mechanism is highly frequency dependent. Thus, IbTX had virtually no effect at spike frequencies < 40 Hz. Furthermore, extracellular field recordings demonstrated (and model simulations supported) that BK channels contribute importantly to high-frequency burst firing in response to excitatory synaptic input to distal dendrites. These results strongly support the idea that BK channels play an important role for early high-frequency, rapidly adapting firing in hippocampal pyramidal neurons, thus promoting the type of bursting that is characteristic of these cells in vivo, during behaviour. PMID:17303637

Reconstruction of the action potential of ventricular myocardial fibres

PubMed Central

Beeler, G. W.; Reuter, H.

1977-01-01

1. A mathematical model of membrane action potentials of mammalian ventricular myocardial fibres is described. The reconstruction model is based as closely as possible on ionic currents which have been measured by the voltage-clamp method. 2. Four individual components of ionic current were formulated mathematically in terms of Hodgkin—Huxley type equations. The model incorporates two voltage- and time-dependent inward currents, the excitatory inward sodium current, iNa, and a secondary or slow inward current, is, primarily carried by calcium ions. A time-independent outward potassium current, iK1, exhibiting inward-going rectification, and a voltage- and time-dependent outward current, ix1, primarily carried by potassium ions, are further elements of the model. 3. The iNa is primarily responsible for the rapid upstroke of the action potential, while the other current components determine the configuration of the plateau of the action potential and the re-polarization phase. The relative importance of inactivation of is and of activation of ix1 for termination of the plateau is evaluated by the model. 4. Experimental phenomena like slow recovery of the sodium system from inactivation, frequency dependence of the action potential duration, all-or-nothing re-polarization, membrane oscillations are adequately described by the model. 5. Possible inadequacies and shortcomings of the model are discussed. PMID:874889

Comprehensive Analyses of Ventricular Myocyte Models Identify Targets Exhibiting Favorable Rate Dependence

PubMed Central

Bugana, Marco; Severi, Stefano; Sobie, Eric A.

2014-01-01

Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP). The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD) antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz) and fast (2 Hz) rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of AP duration rate dependence, and illustrates a strategy for the design of potentially beneficial antiarrhythmic drugs. PMID:24675446

Comprehensive analyses of ventricular myocyte models identify targets exhibiting favorable rate dependence.

PubMed

Cummins, Megan A; Dalal, Pavan J; Bugana, Marco; Severi, Stefano; Sobie, Eric A

2014-03-01

Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP). The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD) antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz) and fast (2 Hz) rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of AP duration rate dependence, and illustrates a strategy for the design of potentially beneficial antiarrhythmic drugs.

Early afterdepolarizations promote transmural reentry in ischemic human ventricles with reduced repolarization reserve

PubMed Central

Dutta, Sara; Mincholé, Ana; Zacur, Ernesto; Quinn, T. Alexander; Taggart, Peter; Rodriguez, Blanca

2016-01-01

Aims Acute ischemia is a major cause of sudden arrhythmic death, further promoted by potassium current blockers. Macro-reentry around the ischemic region and early afterdepolarizations (EADs) caused by electrotonic current have been suggested as potential mechanisms in animal and isolated cell studies. However, ventricular and human-specific arrhythmia mechanisms and their modulation by repolarization reserve remain unclear. The goal of this paper is to unravel multiscale mechanisms underlying the modulation of arrhythmic risk by potassium current (IKr) block in human ventricles with acute regional ischemia. Methods and results A human ventricular biophysically-detailed model, with acute regional ischemia is constructed by integrating experimental knowledge on the electrophysiological ionic alterations caused by coronary occlusion. Arrhythmic risk is evaluated by determining the vulnerable window (VW) for reentry following ectopy at the ischemic border zone. Macro-reentry around the ischemic region is the main reentrant mechanism in the ischemic human ventricle with increased repolarization reserve due to the ATP-sensitive potassium current (IK(ATP)) activation. Prolongation of refractoriness by 4% caused by 30% IKr reduction counteracts the establishment of macro-reentry and reduces the VW for reentry (by 23.5%). However, a further decrease in repolarization reserve (50% IKr reduction) is less anti-arrhythmic despite further prolongation of refractoriness. This is due to the establishment of transmural reentry enabled by electrotonically-triggered EADs in the ischemic border zone. EADs are produced by L-type calcium current (ICaL) reactivation due to prolonged low amplitude electrotonic current injected during the repolarization phase. Conclusions Electrotonically-triggered EADs are identified as a potential mechanism facilitating intramural reentry in a regionally-ischemic human ventricles model with reduced repolarization reserve. PMID:26850675

Pharmacological characterization of ionic currents that regulate high-frequency spontaneous activity of electromotor neurons in the weakly electric fish, Apteronotus leptorhynchus.

PubMed

Smith, G Troy

2006-01-01

The neural circuit that controls the electric organ discharge (EOD) of the brown ghost knifefish (Apteronotus leptorhynchus) contains two spontaneous oscillators. Both pacemaker neurons in the medulla and electromotor neurons (EMNs) in the spinal cord fire spontaneously at frequencies of 500-1,000 Hz to control the EOD. These neurons continue to fire in vitro at frequencies that are highly correlated with in vivo EOD frequency. Previous studies used channel blocking drugs to pharmacologically characterize ionic currents that control high-frequency firing in pacemaker neurons. The goal of the present study was to use similar techniques to investigate ionic currents in EMNs, the other type of spontaneously active neuron in the electromotor circuit. As in pacemaker neurons, high-frequency firing of EMNs was regulated primarily by tetrodotoxin-sensitive sodium currents and by potassium currents that were sensitive to 4-aminopyridine and kappaA-conotoxin SIVA, but resistant to tetraethylammonium. EMNs, however, differed from pacemaker neurons in their sensitivity to some channel blocking drugs. Alpha-dendrotoxin, which blocks a subset of Kv1 potassium channels, increased firing rates in EMNs, but not pacemaker neurons; and the sodium channel blocker muO-conotoxin MrVIA, which reduced firing rates of pacemaker neurons, had no effect on EMNs. These results suggest that similar, but not identical, ionic currents regulate high-frequency firing in EMNs and pacemaker neurons. The differences in the ionic currents expressed in pacemaker neurons and EMNs might be related to differences in the morphology, connectivity, or function of these two cell types.

Potassium intake and risk of incident type 2 diabetes mellitus: the Coronary Artery Risk Development in Young Adults (CARDIA) Study

PubMed Central

Colangelo, L. A.; Yeh, H. C.; Anderson, C. A.; Daviglus, M. L.; Liu, K.; Brancati, F. L.

2014-01-01

Aims/hypothesis Serum potassium has been found to be a significant predictor of diabetes risk, but the effect of dietary potassium on diabetes risk is not clear. We sought to determine if dietary potassium is associated with risk of incident type 2 diabetes in young adults. Methods We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Potassium intake was measured by (1) an average of three 24 h urinary potassium collections at the 5-year study visit, and (2) the CARDIA dietary assessment instrument at baseline. Incident type 2 diabetes cases were ascertained on the basis of use of diabetes medication and laboratory measurements. Analyses were adjusted for relevant confounders including intake of fruit and vegetables and other dietary factors. Results Of 1,066 participants with urinary potassium measurements, 99 (9.3%) developed diabetes over 15 years of follow-up. In multivariate models, adults in the lowest urinary potassium quintile were more than twice as likely to develop diabetes as their counterparts in the highest quintile (HR 2.45; 95% CI 1.08, 5.59). Of 4,754 participants with dietary history measurements, 373 (7.8%) developed diabetes over 20 years of follow-up. In multivariate models, African-Americans had a significantly increased risk of diabetes with lower potassium intake, which was not found in whites. Conclusions/interpretation Low dietary potassium is associated with increased risk of incident diabetes in African-Americans. Randomised clinical trials are needed to determine if potassium supplementation, from either dietary or pharmacological sources, could reduce the risk of diabetes, particularly in higher-risk populations. PMID:22322920

‘And then there were three’: highly efficient uptake of potassium by foliar trichomes of epiphytic bromeliads

PubMed Central

Winkler, Uwe; Zotz, Gerhard

2010-01-01

Background and Aims Vascular epiphytes have to acquire nutrients from atmospheric wash out, stem-flow, canopy soils and trapped litter. Physiological studies on the adaptations to nutrient acquisition and plant utilization of nutrients have focused on phosphorus and nitrogen; potassium, as a third highly abundant nutrient element, has received minor attention. In the present study, potassium uptake kinetics by leaves, within-plant distribution and nutrient accumulation were analysed to gain an improved understanding of physiological adaptations to non-terrestrial nutrient supply of plants. Methods Radioactively labelled 86RbCl was used as an analogue to study uptake kinetics of potassium absorbed from tanks of epiphytes, its plant distribution and the correlation between uptake efficiency and abundance of trichomes, functioning as uptake organs of leaves. Potassium in leaves was additionally analysed by atomic absorption spectroscopy to assess plant responses to potassium deficiency. Key Results Labelled rubidium was taken up from tanks over a wide range of concentrations, 0·01–90 mm, which was achieved by two uptake systems. In four tank epiphytes, the high-affinity transporters had average Km values of 41·2 µm, and the low-affinity transporters average Km values of 44·8 mm. Further analysis in Vriesea splenriet showed that high-affinity uptake of rubidium was an ATP-dependent process, while low-affinity uptake was mediated by a K+-channel. The kinetic properties of both types of transporters are comparable with those of potassium transporters in roots of terrestrial plants. Specific differences in uptake velocities of epiphytes are correlated with the abundance of trichomes on their leaf surfaces. The main sinks for potassium were fully grown leaves. These leaves thus function as internal potassium sources, which allow growth to be maintained during periods of low external potassium availability. Conclusions Vascular epiphytes possess effective mechanisms to take up potassium from both highly diluted and highly concentrated solutions, enabling the plant to incorporate this nutrient element quickly and almost quantitatively from tank solutions. A surplus not needed for current metabolism is stored, i.e. plants show luxury consumption. PMID:20542886

Environmentally Benign Aircraft Anti-icing and Deicing Fluids Based on Cost Effective, Bio-based Ingredients

DTIC Science & Technology

2012-09-01

xanthan gum, welan gum, or carraggenan gum.(13) Examples of particulate thickeners include lightly cross-linked polyacrylic acid. Both types of ...based formulation.(14) The currently used Type IV AAFs are believed to primarily use polyacrylic acid (PAA) polymer, stabilized by potassium ...Prescribed by ANSI-Std Z39-18 REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information

Potassium-doped n-type bilayer graphene

NASA Astrophysics Data System (ADS)

Yamada, Takatoshi; Okigawa, Yuki; Hasegawa, Masataka

2018-01-01

Potassium-doped n-type bilayer graphene was obtained. Chemical vapor deposited bilayer and single layer graphene on copper (Cu) foils were used. After etching of Cu foils, graphene was dipped in potassium hydroxide aqueous solutions to dope potassium. Graphene on silicon oxide was characterized by X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDX), and Raman spectroscopy. Both XPS and EDX spectra indicated potassium incorporation into the bilayer graphene via intercalation between the graphene sheets. The downward shift of the 2D peak position of bilayer graphene after the potassium hydroxide (KOH) treatment was confirmed in Raman spectra, indicating that the KOH-treated bilayer graphene was doped with electrons. Electrical properties were measured using Hall bar structures. The Dirac points of bilayer graphene were shifted from positive to negative by the KOH treatment, indicating that the KOH-treated bilayer graphene was n-type conduction. For single layer graphene after the KOH treatment, although electron doping was confirmed from Raman spectra, the peak of potassium in the X-ray photoelectron spectroscopy (XPS) spectrum was not detected. The Dirac points of single layer graphene with and without the KOH treatment showed positive.

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

PubMed

Tomasello, Danielle L; Hurley, Edward; Wrabetz, Lawrence; Bhattacharjee, Arin

2017-01-01

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.

Potassium Secondary Batteries.

PubMed

Eftekhari, Ali; Jian, Zelang; Ji, Xiulei

2017-02-08

Potassium may exhibit advantages over lithium or sodium as a charge carrier in rechargeable batteries. Analogues of Prussian blue can provide millions of cyclic voltammetric cycles in aqueous electrolyte. Potassium intercalation chemistry has recently been demonstrated compatible with both graphite and nongraphitic carbons. In addition to potassium-ion batteries, potassium-O 2 (or -air) and potassium-sulfur batteries are emerging. Additionally, aqueous potassium-ion batteries also exhibit high reversibility and long cycling life. Because of potentially low cost, availability of basic materials, and intriguing electrochemical behaviors, this new class of secondary batteries is attracting much attention. This mini-review summarizes the current status, opportunities, and future challenges of potassium secondary batteries.

Dendritic A-type potassium channel subunit expression in CA1 hippocampal interneurons.

PubMed

Menegola, M; Misonou, H; Vacher, H; Trimmer, J S

2008-06-26

Voltage-gated potassium (Kv) channels are important and diverse determinants of neuronal excitability and exhibit specific expression patterns throughout the brain. Among Kv channels, Kv4 channels are major determinants of somatodendritic A-type current and are essential in controlling the amplitude of backpropagating action potentials (BAPs) into neuronal dendrites. BAPs have been well studied in a variety of neurons, and have been recently described in hippocampal and cortical interneurons, a heterogeneous population of GABAergic inhibitory cells that regulate activity of principal cells and neuronal networks. We used well-characterized mouse monoclonal antibodies against the Kv4.3 and potassium channel interacting protein (KChIP) 1 subunits of A-type Kv channels, and antibodies against different interneuron markers in single- and double-label immunohistochemistry experiments to analyze the expression patterns of Kv4.3 and KChIP1 in hippocampal Ammon's horn (CA1) neurons. Immunohistochemistry was performed on 40 mum rat brain sections using nickel-enhanced diaminobenzidine staining or multiple-label immunofluorescence. Our results show that Kv4.3 and KChIP1 component subunits of A-type channels are co-localized in the soma and dendrites of a large number of GABAergic hippocampal interneurons. These subunits co-localize extensively but not completely with markers defining the four major interneuron subpopulations tested (parvalbumin, calbindin, calretinin, and somatostatin). These results suggest that CA1 hippocampal interneurons can be divided in two groups according to the expression of Kv4.3/KChIP1 channel subunits. Antibodies against Kv4.3 and KChIP1 represent an important new tool for identifying a subpopulation of hippocampal interneurons with a unique dendritic A-type channel complement and ability to control BAPs.

Inhibitory Effects of Honokiol on the Voltage-Gated Potassium Channels in Freshly Isolated Mouse Dorsal Root Ganglion Neurons.

PubMed

Sheng, Anqi; Zhang, Yan; Li, Guang; Zhang, Guangqin

2018-02-01

Voltage-gated potassium (K V ) currents, subdivided into rapidly inactivating A-type currents (I A ) and slowly inactivating delayed rectifier currents (I K ), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on K V currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I A and I K in concentration-dependent manner. The IC 50 values for block of I A and I K were 30.5 and 25.7 µM, respectively. Hon (30 µM) shifted the steady-state activation curves of I A and I K to positive potentials by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state of I A were unaffected. These results suggest that Hon preferentially interacts with the active states of the I A and I K channels, and has no effect on the resting state and inactivated state of the I A channel. Blockade on K + channels by Hon may contribute to its antinociceptive effect, especially anti-inflammatory pain.

Control of resting membrane potential by delayed rectifier potassium currents in ferret airway smooth muscle cells.

PubMed Central

Fleischmann, B K; Washabau, R J; Kotlikoff, M I

1993-01-01

1. In order to determine the physiological role of specific potassium currents in airway smooth muscle, potassium currents were measured in freshly dissociated ferret trachealis cells using the nystatin-permeabilized, whole-cell method, at 35 degrees C. 2. The magnitude of the outward currents was markedly increased as bath temperature was increased from 22 to 35 degrees C. This increase was primarily due to the increase in maximum potassium conductance (gK,max), although there was also a small leftward shift in the relationship between gK and voltage at higher temperatures. The maximum conductance and the kinetics of current activation and inactivation were also temperature dependent. At 35 degrees C, gating of the current was steeply voltage dependent between -40 and 0 mV. Current activation was well fitted by fourth-order kinetics; the mean time constants of activation (30 mV clamp step) were 1.09 +/- 0.17 and 1.96 +/- 0.27 ms at 35 and 22 degrees C, respectively. 3. Outward currents using the nystatin method were qualitatively similar to delayed rectifier currents recorded in dialysed cells with high calcium buffering capacity solutions. 4-Aminopyridine (4-AP; 2 mM), a specific blocker of delayed rectifier potassium channels in this tissue, inhibited over 80% of the outward current evoked by voltage-clamp steps to between -10 and +20 mV (n = 6). Less than 5% of the outward current was blocked over the same voltage range by charybdotoxin (100 nM; n = 15), a specific antagonist of large-conductance, calcium-activated potassium channels in this tissue. 4. The degree to which delayed rectifier and calcium-activated potassium conductances control resting membrane potential was examined in current-clamp experiments. The resting membrane potential of current clamped cells was -33.6 +/- 1.0 mV (n = 62). Application of 4-AP (2 mM) resulted in a 14.4 +/- 1.0 mV depolarization (n = 8) and an increase in input resistance. Charybdotoxin (100 nM) had no effect on resting membrane potential (n = 6). 5. Force measurements were made in isolated strips of trachealis muscle to determine the effect of pharmacological blockade of individual potassium conductances on resting tone. In the presence of tetrodotoxin (1 microM) and atropine (1 microM), 4-AP increased baseline tension in a dose-dependent manner, with an EC50 of 1.8 mM (n = 13); application of 5 mM 4-AP increased tone to 86.8 +/- 8.1% of that produced by 1 microM methacholine, and this tone was almost completely inhibited by nifedipine (1 microM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8271220

Potassium supply and homeostasis in the osmotolerant non-conventional yeasts Zygosaccharomyces rouxii differ from Saccharomyces cerevisiae.

PubMed

Stříbný, Jiří; Kinclová-Zimmermannová, Olga; Sychrová, Hana

2012-12-01

Three different transport systems exist to accumulate a sufficient amount of potassium cations in yeasts. The most common of these are Trk-type transporters, which are used by all yeast species. Though most yeast species employ two different types of transporters, we only identified one gene encoding a potassium uptake system (Trk-type) in the genome of the highly osmotolerant yeast Zygosaccharomyces rouxii, and our results showed that ZrTrk1 is its major (and probably only) specific potassium uptake system. When expressed in Saccharomyces cerevisiae, the product of the ZrTRK1 gene is localized to the plasma membrane and its presence efficiently complements the phenotypes of S. cerevisiae trk1∆ trk2∆ cells. Deletion of the ZrTRK1 gene resulted in Z. rouxii cells being almost incapable of growth at low K(+) concentrations and it changed some cell physiological parameters in a way that differs from S. cerevisiae. In contrast to S. cerevisiae, Z. rouxii cells without the TRK1 gene contained less potassium than the control cells and their plasma membrane was significantly hyperpolarized compared with those of the parental strain when grown in the presence of 100 mM KCl. On the other hand, subsequent potassium starvation led to a substantial depolarization which is again different from S. cerevisiae. Plasma-membrane hyperpolarization did not prevent the efflux of potassium from Z. rouxii trk1Δ cells during potassium starvation, and the activity of ZrPma1 is less affected by the absence of ZrTRK1 than in S. cerevisiae. The use of a newly constructed Z. rouxii-specific plasmid for the expression of pHluorin showed that the intracellular pH of the Z. rouxii wild type and the trk1∆ mutant is not significantly different. Together with the fact that Z. rouxii cells contain a significantly lower amount of intracellular potassium than identically grown S. cerevisiae cells, our results suggest that this highly osmotolerant yeast species maintain its intracellular pH and potassium homeostasis in way(s) partially distinct from S. cerevisiae.

A human intermediate conductance calcium-activated potassium channel.

PubMed

Ishii, T M; Silvia, C; Hirschberg, B; Bond, C T; Adelman, J P; Maylie, J

1997-10-14

An intermediate conductance calcium-activated potassium channel, hIK1, was cloned from human pancreas. The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is approximately 50% conserved. hIK1 mRNA was detected in peripheral tissues but not in brain. Expression of hIK1 in Xenopus oocytes gave rise to inwardly rectifying potassium currents, which were activated by submicromolar concentrations of intracellular calcium (K0.5 = 0.3 microM). Although the K0.5 for calcium was similar to that of small conductance calcium-activated potassium channels, the slope factor derived from the Hill equation was significantly reduced (1.7 vs. 3. 5). Single-channel current amplitudes reflected the macroscopic inward rectification and revealed a conductance level of 39 pS in the inward direction. hIK1 currents were reversibly blocked by charybdotoxin (Ki = 2.5 nM) and clotrimazole (Ki = 24.8 nM) but were minimally affected by apamin (100 nM), iberiotoxin (50 nM), or ketoconazole (10 microM). These biophysical and pharmacological properties are consistent with native intermediate conductance calcium-activated potassium channels, including the erythrocyte Gardos channel.

Kv7 potassium channel subunits and M currents in cultured hippocampal interneurons.

PubMed

Grigorov, Alexej; Moskalyuk, Anastasia; Kravchenko, Mykola; Veselovsky, Nikolai; Verkhratsky, Alexei; Fedulova, Svetlana

2014-09-01

Potassium channels of the Kv7 family that mediate the non-inactivating M current regulate the excitability of many types of neurons in the central nervous system, including some in the hippocampus. We report here that individual interneurons from newborn rat hippocampi in long-term culture strongly express messenger RNA specific for Kv7.2 and Kv7.3 and, to a lesser extent, Kv7.5 channel subunits but not for the Kv7.4 subunit. An M-like current was electrophysiologically identified in two subpopulations of interneurons distinct in their spiking behaviour (regular or fast spiking). The M-channel enhancer retigabine reduced interneuronal excitability by constraining the number of action potentials generated during imposed depolarisations; this effect was inhibited by specific the M-channel blocking drugs. In paired synaptically connected interneuron-target cell recordings, anatomically localised applications of retigabine indicated that M channels were present in both the interneuron soma and its GABA-ergic inhibitory axon. We conclude that M-channel subunits and functional M channels are broadly expressed in hippocampal interneurons and their axons and are potentially capable of strongly regulating their firing properties.

Computational Reconstruction of Pacemaking and Intrinsic Electroresponsiveness in Cerebellar Golgi Cells

PubMed Central

Solinas, Sergio; Forti, Lia; Cesana, Elisabetta; Mapelli, Jonathan; De Schutter, Erik; D'Angelo, Egidio

2007-01-01

The Golgi cells have been recently shown to beat regularly in vitro (Forti et al., 2006. J. Physiol. 574, 711–729). Four main currents were shown to be involved, namely a persistent sodium current (I Na-p), an h current (I h), an SK-type calcium-dependent potassium current (I K-AHP), and a slow M-like potassium current (I K-slow). These ionic currents could take part, together with others, also to different aspects of neuronal excitability like responses to depolarizing and hyperpolarizing current injection. However, the ionic mechanisms and their interactions remained largely hypothetical. In this work, we have investigated the mechanisms of Golgi cell excitability by developing a computational model. The model predicts that pacemaking is sustained by subthreshold oscillations tightly coupled to spikes. I Na-p and I K-slow emerged as the critical determinants of oscillations. I h also played a role by setting the oscillatory mechanism into the appropriate membrane potential range. I K-AHP, though taking part to the oscillation, appeared primarily involved in regulating the ISI following spikes. The combination with other currents, in particular a resurgent sodium current (I Na-r) and an A-current (I K-A), allowed a precise regulation of response frequency and delay. These results provide a coherent reconstruction of the ionic mechanisms determining Golgi cell intrinsic electroresponsiveness and suggests important implications for cerebellar signal processing, which will be fully developed in a companion paper (Solinas et al., 2008. Front. Neurosci. 2:4). PMID:18946520

Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro-B-type natriuretic peptide levels: An individual patient data analysis.

PubMed

Salah, Khibar; Pinto, Yigal M; Eurlings, Luc W; Metra, Marco; Stienen, Susan; Lombardi, Carlo; Tijssen, Jan G; Kok, Wouter E

2015-09-01

Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF. Our study is a pooled individual patient data analysis assembled from 3 prospective cohorts comprising 754 patients hospitalized for ADHF. The endpoint was all-cause mortality within 180 days after discharge. Serum potassium levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission and at discharge. A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality-a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables-the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73). A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Potassium and Health123

PubMed Central

Weaver, Connie M.

2013-01-01

Potassium was identified as a shortfall nutrient by the Dietary Guidelines for Americans 2010 Advisory Committee. The committee concluded that there was a moderate body of evidence of the association between potassium intake and blood pressure reduction in adults, which in turn influences the risk of stroke and coronary heart disease. Evidence is also accumulating of the protective effect of adequate dietary potassium on age-related bone loss and reduction of kidney stones. These benefits depend on organic anions associated with potassium as occurs in foods such as fruits and vegetables, in contrast to similar blood pressure-lowering benefits of potassium chloride. Benefits to blood pressure and bone health may occur at levels below current recommendations for potassium intake, especially from diet, but dose-response trials are needed to confirm this. Nevertheless, intakes considerably above current levels are needed for optimal health, and studies evaluating small increases in fruit and vegetable intake on bone and heart outcomes for short periods have had disappointing results. In modern societies, Western diets have led to a decrease in potassium intake with reduced consumption of fruits and vegetables with a concomitant increase in sodium consumption through increased consumption of processed foods. Consumption of white vegetables is associated with decreased risk of stroke, possibly related to their high potassium content. Potatoes are the highest source of dietary potassium, but the addition of salt should be limited. Low potassium-to-sodium intake ratios are more strongly related to cardiovascular disease risk than either nutrient alone. This relationship deserves further attention for multiple target tissue endpoints. PMID:23674806

Free energy dissipation of the spontaneous gating of a single voltage-gated potassium channel.

PubMed

Wang, Jia-Zeng; Wang, Rui-Zhen

2018-02-01

Potassium channels mainly contribute to the resting potential and re-polarizations, with the potassium electrochemical gradient being maintained by the pump Na + /K + -ATPase. In this paper, we construct a stochastic model mimicking the kinetics of a potassium channel, which integrates temporal evolving of the membrane voltage and the spontaneous gating of the channel. Its stationary probability density functions (PDFs) are found to be singular at the boundaries, which result from the fact that the evolving rates of voltage are greater than the gating rates of the channel. We apply PDFs to calculate the power dissipations of the potassium current, the leakage, and the gating currents. On a physical perspective, the essential role of the system is the K + -battery charging the leakage (L-)battery. A part of power will inevitably be dissipated among the process. So, the efficiency of energy transference is calculated.

Free energy dissipation of the spontaneous gating of a single voltage-gated potassium channel

NASA Astrophysics Data System (ADS)

Wang, Jia-Zeng; Wang, Rui-Zhen

2018-02-01

Potassium channels mainly contribute to the resting potential and re-polarizations, with the potassium electrochemical gradient being maintained by the pump Na+/K+-ATPase. In this paper, we construct a stochastic model mimicking the kinetics of a potassium channel, which integrates temporal evolving of the membrane voltage and the spontaneous gating of the channel. Its stationary probability density functions (PDFs) are found to be singular at the boundaries, which result from the fact that the evolving rates of voltage are greater than the gating rates of the channel. We apply PDFs to calculate the power dissipations of the potassium current, the leakage, and the gating currents. On a physical perspective, the essential role of the system is the K+-battery charging the leakage (L-)battery. A part of power will inevitably be dissipated among the process. So, the efficiency of energy transference is calculated.

[Electrophysiological study on rat conduit pulmonary artery smooth muscle cells under normoxia and acute hypoxia].

PubMed

Hu, Ying; Zou, Fei; Cai, Chun-Qing; Wu, Hang-Yu; Yun, Hai-Xia; Chen, Yun-Tian; Jin, Guo-En; Ge, Ri-Li

2006-10-25

The present study was designed to investigate the electrophysiological characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were divided into acute hypoxia preconditioned group and normoxia group. Hypoxia solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min before cell perfusion. Potassium currents were compared between these two groups using whole-cell patch clamp technique. The total outward current of PASMCs was measured under normoxia condition when iBTX [specific blocking agent of large conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath solution. PASMCs were classified into three types according to their size, shape and electrophysiological characteristics. Type I cells are the smallest with spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show the biggest size with banana-like appearance. Type III cells have the similar size with type I, and present intermediary shape between type I and type II. iBTX had little effect on the total outward current in type I cells, while 4-AP almost completely blocked it. Most of the total outward current in type II cells was inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells, the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/-33.6) pA for type I cells (P<0.01); (438.3+/-42.8) pA to (277.5+/-44.7) pA for type II cells (P<0.01); (1 042.0+/-37.2) pA to (613.6+/-23.8) pA for type III (P<0.01), and raised the resting membrane potentials (E(m)) in all these three types of cells: (-41.6+/-1.6) mV to (-18.6+/-1.5) mV (P<0.01), (-42.3+/-3.8) mV to (-30.6+/-3.0) mV (P<0.01), (-43.3+/-1.6) mV to (-28.4+/-1.4) mV (P<0.01), for type I, II, III cells, respectively. These results suggest that acute hypoxia suppresses the potassium current and improves the E(m) in PASMCs. These effects may be involved in the modulation of constriction/relaxation of conduit artery under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these three types of PASMCs might account for their different constriction/relaxation response to acute hypoxia.

The effects of piracetam and its novel peptide analogue GVS-111 on neuronal voltage-gated calcium and potassium channels.

PubMed

Solntseva, E I; Bukanova, J V; Ostrovskaya, R U; Gudasheva, T A; Voronina, T A; Skrebitsky, V G

1997-07-01

1. With the use of the two-microelectrode voltage-clamp method, three types of voltage-activated ionic currents were examined in isolated neurons of the snail Helix pomatia: high-threshold Ca2+ current (ICa), high-threshold Ca(2+)-dependent K+ current (IK(Ca)) and high-threshold K+ current independent of Ca2+ (IK(V)). 2. The effect of bath application of the nootropics piracetam and a novel piracetam peptide analog, ethyl ester of N-phenyl-acetyl-L-prolyl-glycine (GVS-111), on these three types of voltage-activated ionic currents was studied. 3. In more than half of the tested cells, ICa was resistant to both piracetam and GVS-111. In the rest of the cells, ICa decreased 19 +/- 7% with 2 mM of piracetam and 39 +/- 14% with 2 microM of GVS-111. 4. IK(V) in almost all cells tested was resistant to piracetam at concentrations up to 2 mM. However, IK(V) in two-thirds of the cells was sensitive to GVS-111, being suppressed 49 +/- 18% with 1 microM GVS-111. 5. IK(Ca) appeared to be the most sensitive current of those studied to both piracetam and GVS-111. Piracetam at 1 mM and GVS-111 at 0.1 microM decreased the amplitude of IK(Ca) in most of the cells examined by 49 +/- 19% and 69 +/- 24%, respectively. 6. The results suggest that piracetam and GVS-111 suppression of voltage-activated calcium and potassium currents of the neuronal membrane may regulate (both up and down) Ca2+ influx into neurons.

Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis

PubMed Central

Iwai, Yuta; Shibuya, Kazumoto; Misawa, Sonoko; Sekiguchi, Yukari; Watanabe, Keisuke; Amino, Hiroshi; Kuwabara, Satoshi

2016-01-01

Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS), suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP) amplitude (index of motor neuronal loss) and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44), ALS patients (n = 140) had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p < 0.05), greater threshold changes in depolarizing threshold electrotonus (p < 0.05) and depolarizing current threshold relationship (i.e. less accommodation; (p < 0.05), greater superexcitability (a measure of fast potassium current; p < 0.05) and reduced late subexcitability (a measure of slow potassium current; p < 0.05), suggesting increased persistent sodium currents and decreased potassium currents. The reduced potassium currents were found even in the patient subgroups with normal CMAP (> 5mV). Regression analyses showed that SDTC (R = -0.22) and depolarizing threshold electrotonus (R = -0.22) increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS. PMID:27383069

Potassium Loss during Galvanotaxis of Slime Mold

PubMed Central

Anderson, John D.

1962-01-01

The posterior reticulated regions of the plasmodia of the slime mold, Physarum polycephalum, whose migration has been oriented by direct current (3.0 to 5.0 µa/mm2 in the agar substrate), contain 30 per cent less potassium than the advancing non-reticulated region. The anterior regions have the same potassium concentration as that of the controls, approximately 32 meq/kg wet weight. Differences in potassium concentration between anterior and posterior regions of control plasmodia, not oriented by electric current, are less than 5 per cent. Sodium, in contrast to potassium, is generally less concentrated in the anterior than in the posterior regions of electrically oriented plasmodia, but sodium concentrations are extremely variable. No significant difference in protein concentration was found between oriented and control plasmodia. Thirty-five per cent of the total potassium, but none of the sodium, is found in acidified ethanol precipitates from plasmodial homogenates. Potassium, but not sodium, appears to be closely associated with processes which differentiate anterior from posterior in an oriented plasmodium. PMID:13861244

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

PubMed

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.

A bursting potassium channel in isolated cholinergic synaptosomes of Torpedo electric organ.

PubMed Central

Edry-Schiller, J; Ginsburg, S; Rahamimoff, R

1991-01-01

1. Pinched-off cholinergic nerve terminals (synaptosomes) prepared from the electric organ of Torpedo ocelata were fused into large structures (greater than 20 microns) using dimethyl sulphoxide and polyethylene glycol 1500, as previously described for synaptic vesicles from the same organ. 2. The giant fused synaptosomes were easily amenable to the patch clamp technique and 293 seals with a resistance greater than 4 G omega were obtained in the 'cell-attached' configuration. In a large fraction of the experiments, an 'inside-out' patch configuration was achieved. 3. Several types of unitary ionic currents were observed. This study describes the most frequently observed single-channel activity which was found in 247 out of the 293 membrane patches (84.3%). 4. The single-channel current-voltage relation was linear between -60 and 20 mV and showed a slope conductance of 23.8 +/- 1.3 pS when the pipette contained 350-390 mM-Na+ and the bath facing the inside of the synaptosomal membrane contained 390 mM-K+. 5. From extrapolated reversal potential measurements, it was concluded that this channel has a large selectivity for K+ over Na+ (70.4 +/- 11.5, mean +/- S.E.M.). Chloride ions are not transported significantly through this potassium channel. 6. This potassium channel has a low probability of opening. The probability of being in the open state increases upon depolarization and reaches about 1% when the inside of the patch is 20 mV positive compared to the pipette side. 7. The mean channel open time increases with depolarization; thus the product current x time (= charge) also increases upon depolarization, showing properties of an outward rectifier. 8. The potassium channel in the giant synaptosome membrane has a bursting behaviour. Open-time distribution, closed-time distribution and a Poisson analysis indicate that the minimal kinetic scheme requires one open state and three closed states. PMID:1654418

21 CFR 184.1639 - Potassium lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is prepared commercially by the neutralization of lactic acid with potassium hydroxide. (b) The ingredient... current good manufacturing practice. (d) Prior sanctions for this ingredient different from the uses...

21 CFR 184.1639 - Potassium lactate.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is prepared commercially by the neutralization of lactic acid with potassium hydroxide. (b) The ingredient... current good manufacturing practice. (d) Prior sanctions for this ingredient different from the uses...

21 CFR 184.1639 - Potassium lactate.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is prepared commercially by the neutralization of lactic acid with potassium hydroxide. (b) The ingredient... current good manufacturing practice. (d) Prior sanctions for this ingredient different from the uses...

21 CFR 184.1639 - Potassium lactate.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is prepared commercially by the neutralization of lactic acid with potassium hydroxide. (b) The ingredient... current good manufacturing practice. (d) Prior sanctions for this ingredient different from the uses...

Dopamine/Tyrosine Hydroxylase Neurons of the Hypothalamic Arcuate Nucleus Release GABA, Communicate with Dopaminergic and Other Arcuate Neurons, and Respond to Dynorphin, Met-Enkephalin, and Oxytocin

PubMed Central

Zhang, Xiaobing

2015-01-01

We employ transgenic mice with selective expression of tdTomato or cre recombinase together with optogenetics to investigate whether hypothalamic arcuate (ARC) dopamine/tyrosine hydroxylase (TH) neurons interact with other ARC neurons, how they respond to hypothalamic neuropeptides, and to test whether these cells constitute a single homogeneous population. Immunostaining with dopamine and TH antisera was used to corroborate targeted transgene expression. Using whole-cell recording on a large number of neurons (n = 483), two types of neurons with different electrophysiological properties were identified in the dorsomedial ARC where 94% of TH neurons contained immunoreactive dopamine: bursting and nonbursting neurons. In contrast to rat, the regular oscillations of mouse bursting neurons depend on a mechanism involving both T-type calcium and A-type potassium channel activation, but are independent of gap junction coupling. Optogenetic stimulation using cre recombinase-dependent ChIEF-AAV-DJ expressed in ARC TH neurons evoked postsynaptic GABA currents in the majority of neighboring dopamine and nondopamine neurons, suggesting for the first time substantial synaptic projections from ARC TH cells to other ARC neurons. Numerous met-enkephalin (mENK) and dynorphin-immunoreactive boutons appeared to contact ARC TH neurons. mENK inhibited both types of TH neuron through G-protein coupled inwardly rectifying potassium currents mediated by δ and μ opioid receptors. Dynorphin-A inhibited both bursting and nonbursting TH neurons by activating κ receptors. Oxytocin excited both bursting and nonbursting neurons. These results reveal a complexity of TH neurons that communicate extensively with neurons within the ARC. SIGNIFICANCE STATEMENT Here, we show that the great majority of mouse hypothalamic arcuate nucleus (ARC) neurons that synthesize TH in the dorsomedial ARC also contain immunoreactive dopamine, and show either bursting or nonbursting electrical activity. Unlike rats, the mechanism underlying bursting was not dependent on gap junctions but required T-type calcium and A-type potassium channel activation. Neuropeptides dynorphin and met-enkephalin inhibited dopamine neurons, whereas oxytocin excited them. Most ventrolateral ARC TH cells did not contain dopamine and did not show bursting electrical activity. TH-containing neurons appeared to release synaptic GABA within the ARC onto dopamine neurons and unidentified neurons, suggesting that the cells not only control pituitary hormones but also may modulate nearby neurons. PMID:26558770

Potassium channels: the importance of transport signals.

PubMed

Griffith, L C

2001-03-20

The number, type and distribution of ion channels on a neuron's surface determine its electrical response to stimulation. One way that a cell determines how many molecules of each channel type are sent to the surface has been eludicated in a recent study of intrinsic protein transport signals within potassium channels.

Degradation Effect of Sulfa Antibiotics by Potassium Ferrate Combined with Ultrasound (Fe(VI)-US)

PubMed Central

Zhang, Kejia; Luo, Zhang; Zhang, Tuqiao; Gao, Naiyun; Ma, Yan

2015-01-01

Sulfa antibiotics are a family of typical broad-spectrum antibiotics, which have become one of the most frequently detected antibiotics in water, posing a great threat to human health and ecosystem. Potassium ferrate is a new type of high-efficiency multifunctional water treatment agent, collecting the effects of oxidation, adsorption, flocculation, coagulation, sterilization, and deodorization. Performance and mechanism of degradation of typical broad-spectrum antibiotics by Fe(VI)-US were further studied, investigating the degradation effect of sulfa antibiotics by single ultrasound, single potassium ferrate, and potassium ferrate-ultrasound (Fe(VI)-US). It was found that Fe(VI)-US technology had a significant role in promoting the degradation of sulfa antibiotics via orthogonal experiments. Factors evaluated included sulfa antibiotics type, pH value, potassium ferrate dosage, ultrasonic frequency, and ultrasonic power, with the pH value and potassium ferrate dosage being affected most significantly. One reason for synergy facilitating the degradation is the common oxidation of potassium ferrate and ultrasound, and the other is that Fe(III) produced promotes the degradation rate. According to the product analysis and degradation pathways of three sulfa antibiotics, ferrate-sonication sulfa antibiotics are removed by hydroxyl radical oxidation. PMID:26347876

Degradation Effect of Sulfa Antibiotics by Potassium Ferrate Combined with Ultrasound (Fe(VI)-US).

PubMed

Zhang, Kejia; Luo, Zhang; Zhang, Tuqiao; Gao, Naiyun; Ma, Yan

2015-01-01

Sulfa antibiotics are a family of typical broad-spectrum antibiotics, which have become one of the most frequently detected antibiotics in water, posing a great threat to human health and ecosystem. Potassium ferrate is a new type of high-efficiency multifunctional water treatment agent, collecting the effects of oxidation, adsorption, flocculation, coagulation, sterilization, and deodorization. Performance and mechanism of degradation of typical broad-spectrum antibiotics by Fe(VI)-US were further studied, investigating the degradation effect of sulfa antibiotics by single ultrasound, single potassium ferrate, and potassium ferrate-ultrasound (Fe(VI)-US). It was found that Fe(VI)-US technology had a significant role in promoting the degradation of sulfa antibiotics via orthogonal experiments. Factors evaluated included sulfa antibiotics type, pH value, potassium ferrate dosage, ultrasonic frequency, and ultrasonic power, with the pH value and potassium ferrate dosage being affected most significantly. One reason for synergy facilitating the degradation is the common oxidation of potassium ferrate and ultrasound, and the other is that Fe(III) produced promotes the degradation rate. According to the product analysis and degradation pathways of three sulfa antibiotics, ferrate-sonication sulfa antibiotics are removed by hydroxyl radical oxidation.

A-type potassium channels differentially tune afferent pathways from rat solitary tract nucleus to caudal ventrolateral medulla or paraventricular hypothalamus

PubMed Central

Bailey, T W; Hermes, S M; Whittier, K L; Aicher, S A; Andresen, M C

2007-01-01

The solitary tract nucleus (NTS) conveys visceral information to diverse central networks involved in homeostatic regulation. Although afferent information content arriving at various CNS sites varies substantially, little is known about the contribution of processing within the NTS to these differences. Using retrograde dyes to identify specific NTS projection neurons, we recently reported that solitary tract (ST) afferents directly contact NTS neurons projecting to caudal ventrolateral medulla (CVLM) but largely only indirectly contact neurons projecting to the hypothalamic paraventricular nucleus (PVN). Since intrinsic properties impact information transmission, here we evaluated potassium channel expression and somatodendritic morphology of projection neurons and their relation to afferent information output directed to PVN or CVLM pathways. In slices, tracer-identified projection neurons were classified as directly or indirectly (polysynaptically) coupled to ST afferents by EPSC latency characteristics (directly coupled, jitter < 200 μs). In each neuron, voltage-dependent potassium currents (IK) were evaluated and, in representative neurons, biocytin-filled structures were quantified. Both CVLM- and PVN-projecting neurons had similar, tetraethylammonium-sensitive IK. However, only PVN-projecting NTS neurons displayed large transient, 4aminopyridine-sensitive, A-type currents (IKA). PVN-projecting neurons had larger cell bodies with more elaborate dendritic morphology than CVLM-projecting neurons. ST shocks faithfully (> 75%) triggered action potentials in CVLM-projecting neurons but spike output was uniformly low (< 20%) in PVN-projecting neurons. Pre-conditioning hyperpolarization removed IKA inactivation and attenuated ST-evoked spike generation along PVN but not CVLM pathways. Thus, multiple differences in structure, organization, synaptic transmission and ion channel expression tune the overall fidelity of afferent signals that reach these destinations. PMID:17510187

Ensemble learning for spatial interpolation of soil potassium content based on environmental information.

PubMed

Liu, Wei; Du, Peijun; Wang, Dongchen

2015-01-01

One important method to obtain the continuous surfaces of soil properties from point samples is spatial interpolation. In this paper, we propose a method that combines ensemble learning with ancillary environmental information for improved interpolation of soil properties (hereafter, EL-SP). First, we calculated the trend value for soil potassium contents at the Qinghai Lake region in China based on measured values. Then, based on soil types, geology types, land use types, and slope data, the remaining residual was simulated with the ensemble learning model. Next, the EL-SP method was applied to interpolate soil potassium contents at the study site. To evaluate the utility of the EL-SP method, we compared its performance with other interpolation methods including universal kriging, inverse distance weighting, ordinary kriging, and ordinary kriging combined geographic information. Results show that EL-SP had a lower mean absolute error and root mean square error than the data produced by the other models tested in this paper. Notably, the EL-SP maps can describe more locally detailed information and more accurate spatial patterns for soil potassium content than the other methods because of the combined use of different types of environmental information; these maps are capable of showing abrupt boundary information for soil potassium content. Furthermore, the EL-SP method not only reduces prediction errors, but it also compliments other environmental information, which makes the spatial interpolation of soil potassium content more reasonable and useful.

Gap-Junctional communication between developing Drosophila muscles is essential for their normal development.

PubMed

Todman, M G; Baines, R A; Stebbings, L A; Davies, J A; Bacon, J P

1999-01-01

Recent experiments have demonstrated that a family of proteins, known as the innexins, are structural components of invertebrate gap junctions. The shaking-B (shak-B) locus of Drosophila encodes two members of this emerging family, Shak-B(lethal) and Shak-B(neural). This study focuses on the role of Shak-B gap junctions in the development of embryonic and larval muscle. During embryogenesis, shak-B transcripts are expressed in a subset of the somatic muscles; expression is strong in ventral oblique muscles (VO4-6) but only weak in ventral longitudinals (VL3 and 4). Carboxyfluorescein injected into VO4 of wild-type early stage 16 embryos spreads, via gap junctions, to label adjacent muscles, including VL3 and 4. In shak-B2 embryos (in which the shak-B(neural) function is disrupted), dye injected into VO4 fails to spread into other muscles. In the first instar larva, when dye coupling between muscles is no longer present, another effect of the shak-B2 mutation is revealed by whole-cell voltage clamp. In a calcium-free saline, only two voltage-activated potassium currents are present in wild-type muscles; a fast IA and a slow IK current. In shak-B2 larvae, these two currents are significantly reduced in magnitude in VO4 and 5, but remain normal in VL3. Expression of shak-B(neural) in a shak-B2 background fully rescues both dye coupling in embryonic muscle and whole-cell currents in first instar VO4 and 5. Our observations show that Shak-B(neural) is one of a set of embryonic gap-junction proteins, and that it is required for the normal temporal development of potassium currents in some larval muscles.

Sodium and potassium conductance changes during a membrane action potential.

PubMed

Bezanilla, F; Rojas, E; Taylor, R E

1970-12-01

1. A method for turning a membrane potential control system on and off in less than 10 musec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential.2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential.3. The total membrane conductance taken from these current-voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939).4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin-Huxley equations.5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential.

Gene expression of stretch-activated channels and mechanoelectric feedback in the heart.

PubMed

Kelly, D; Mackenzie, L; Hunter, P; Smaill, B; Saint, D A

2006-07-01

1. Mechanoelectric feedback (MEF) in the heart is the process by which mechanical forces on the myocardium can change its electrical properties. Mechanoelectric feedback has been demonstrated in many animal models, ranging from isolated cells, through isolated hearts to whole animals. In humans, MEF has been demonstrated directly in both the atria and the ventricles. It seems likely that MEF provides either the trigger or the substrate for some types of clinically important arrhythmias. 2. Mechanoelectric feedback may arise because of the presence of stretch-sensitive (or mechano-sensitive) ion channels in the cell membrane of the cardiac myocytes. Two types have been demonstrated: (i) a non-specific cation channel (stretch-activated channel (SAC); conductance of approximately 25 pS); and (ii) a potassium channel with a conductance of approximately 100 pS. The gene coding for the SAC has not yet been identified. The gene for the potassium channel is likely to be TREK, a member of the tandem pore potassium channel gene family. We have recorded stretch-sensitive potassium channels in rat isolated myocytes that have the properties of TREK channels expressed in heterologous systems. 3. It has been shown that TREK mRNA is expressed heterogeneously in the rat ventricular wall, with 17-fold more expression in endocardial compared with epicardial cells. This difference is reflected in the TREK currents recorded from endocardial and epicardial cells using whole-cell patch-clamp techniques, although the difference in current density was less pronounced (approximately threefold). Consistent with this, we show here that when the ventricle is stretched by inflation of an intraventricular balloon in a Langendorff perfused rat isolated heart, action potential shortening was more pronounced in the endocardium (30% shortening at 40 mmHg) compared with that in the epicardium (10% shortening at the same pressure). 4. Computer models of the mechanics of the (pig) heart show pronounced spatial variations in strain in the myocardium with large transmural differences (in the left ventricle in particular) and also large differences between the base and apex of the ventricle. 5. The importance of MEF and the non-homogeneous gene expression and strain distribution for arrhythmias is discussed.

Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse.

PubMed

Carter, D A; Choong, Y-T; Connelly, A A; Bassi, J K; Hunter, N O; Thongsepee, N; Llewellyn-Smith, I J; Fong, A Y; McDougall, S J; Allen, A M

2017-10-01

Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT 1A R) most widely expressed in adult neurons. Activation of the AT 1 R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT 1 R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT 1A R-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT 1A R promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT 1A R-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT 1A R-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT 1A R-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT 1A R-GFP neurons and TH-GFP neurons showed similar AT 1A R-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT 1A R-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing. Copyright © 2017 the American Physiological Society.

The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

PubMed

Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

2015-08-01

The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

Development of potassium ion conducting hollow glass fibers. [potassium sulfur battery

NASA Technical Reports Server (NTRS)

Tsang, F. Y.

1974-01-01

Potassium ion conducting glasses, chemically resistant to potassium, potassium sulfide and sulfur, were made and their possible utility as the membrane material for a potassium/sulfur battery was evaluated. At least one satisfactory candidate was found. It possesses an electrical resistance which makes it usable as a membrane in the form of a fine hollow fiber. It's chemical and electrochemical resistances are excellent. The other aspects of the possible potassium sulfur battery utilizing such fine hollow fibers, including the header (or tube sheet) and a cathode current collector were studied. Several cathode materials were found to be satisfactory. None of the tube sheet materials studied possessed all the desired properties. Multi-fiber cells had very limited life-time due to physical failure of fibers at the fiber/tube sheet junctions.

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

PubMed

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.

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

PubMed

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.

Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vicente, Jose; Johannesen, Lars; Hosseini, Meisam

Drugs that prolong the heart rate corrected QT interval (QTc) on the electrocardiogram (ECG) by blocking the hERG potassium channel and also block inward currents (late sodium or L-type calcium) are not associated with torsade de pointes (e.g. ranolazine and verapamil). Furthermore, identifying ECG signs of late sodium current block could aid in the determination of proarrhythmic risk for new drugs. A new cardiac safety paradigm for drug development (the "CiPA" initiative) will involve the preclinical assessment of multiple human cardiac ion channels and ECG biomarkers are needed to determine if there are unexpected ion channel effects in humans.

Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block

DOE PAGES

Vicente, Jose; Johannesen, Lars; Hosseini, Meisam; ...

2016-12-30

Drugs that prolong the heart rate corrected QT interval (QTc) on the electrocardiogram (ECG) by blocking the hERG potassium channel and also block inward currents (late sodium or L-type calcium) are not associated with torsade de pointes (e.g. ranolazine and verapamil). Furthermore, identifying ECG signs of late sodium current block could aid in the determination of proarrhythmic risk for new drugs. A new cardiac safety paradigm for drug development (the "CiPA" initiative) will involve the preclinical assessment of multiple human cardiac ion channels and ECG biomarkers are needed to determine if there are unexpected ion channel effects in humans.

Rapid Changes of Potassium Concentration at the Outer Surface of Exposed Single Neurons during Membrane Current Flow

PubMed Central

Neher, E.; Lux, H. D.

1973-01-01

K+-sensitive liquid ion-exchanger microelectrodes are shown to be capable of measuring concentration changes which occur on a millisecond time scale. However, some quaternary ammonium ions, such as tetraethylammonium and acetylcholine, are able to block electrode function when present in concentrations as low as 10-4 to 10-3 M. Changes in extracellular potassium concentration caused by spike activity or voltage clamp pulses of exposed single neurons of the snail Helix pomatia may be measured by these electrodes. Quantitative analysis shows that the total amount of excess potassium found in the vicinity of the cell a short time after a clamp pulse, is in relatively good agreement with the amount of potassium carried by the membrane current. PMID:4689624

Effects of KCNQ channel modulators on the M-type potassium current in primate retinal pigment epithelium.

PubMed

Pattnaik, Bikash R; Hughes, Bret A

2012-03-01

Recently, we demonstrated the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts in monkey retinal pigment epithelium (RPE) and showed that the M-type current in RPE cells is blocked by the specific KCNQ channel blocker XE991. Using patch-clamp electrophysiology, we investigated the pharmacological sensitivity of the M-type current in isolated monkey RPE cells to elucidate the subunit composition of the channel. Most RPE cells exhibited an M-type current with a voltage for half-maximal activation of approximately -35 mV. The M-type current activation followed a double-exponential time course and was essentially complete within 1 s. The M-type current was inhibited by micromolar concentrations of the nonselective KCNQ channel blockers linopirdine and XE991 but was relatively insensitive to block by 10 μM chromanol 293B or 135 mM tetraethylammonium (TEA), two KCNQ1 channel blockers. The M-type current was activated by 1) 10 μM retigabine, an opener of all KCNQ channels except KCNQ1, 2) 10 μM zinc pyrithione, which augments all KCNQ channels except KCNQ3, and 3) 50 μM N-ethylmaleimide, which activates KCNQ2, KCNQ4, and KCNQ5, but not KCNQ1 or KCNQ3, channels. Application of cAMP, which activates KCNQ1 and KCNQ4 channels, had no significant effect on the M-type current. Finally, diclofenac, which activates KCNQ2/3 and KCNQ4 channels but inhibits KCNQ5 channels, inhibited the M-type current in the majority of RPE cells but activated it in others. The results indicate that the M-type current in monkey RPE is likely mediated by channels encoded by KCNQ4 and KCNQ5 subunits.

A survey of interstellar neutral potassium. I - Abundances and physical conditions in clouds toward 188 early-type stars

NASA Technical Reports Server (NTRS)

Chaffee, F. H., Jr.; White, R. E.

1982-01-01

Observations of interstellar absorption in the resonance doublet 7664, 7698 A of neutral potassium toward 188 early-type stars at a spectral resolution of 8 km/s are reported. The 7664 A line is successfully separated from nearly coincident telluric O2 absorption for all but a few of the 165 stars for which K I absorption is detected, making possible an abundance analysis by the doublet ratio method. The relationships between the potassium abundances and other atomic abundances, the abundance of molecular hydrogen, and interstellar reddening are investigated.

Involvement of a Gardos-type potassium channel in head activator-induced mitosis of BON cells.

PubMed

Kayser, S T; Ulrich, H; Schaller, H C

1998-06-01

The human neuroendocrine cell line BON was used to study second messengers involved in signal transduction for entry into mitosis. BON cells produce the neuropeptide head activator (HA) and use it as autocrine growth factor. HA stimulates BON cell proliferation by triggering entry into mitosis. HA-induced mitosis is mediated by an inhibitory G protein, the action of which is blocked by pertussis toxin. HA signaling requires inhibition of the cAMP pathway, calcium influx, and hyperpolarization of cells. The latter is a very important and sensitive step involving a calcium-activated potassium channel. Cell cycle progression and proliferation of BON cells are most efficiently inhibited with specific inhibitors of this potassium channel. Pharmacology and RNA analysis suggest identity with the recently cloned Gardos-type potassium channel.

The renal response to potassium stress: integrating past with present.

PubMed

Boyd-Shiwarski, Cary R; Subramanya, Arohan R

2017-09-01

The current review combines past findings with recent advances in our understanding of the homeostatic response to potassium imbalance. Following the ingestion of a dietary potassium load, a combination of extrarenal and renal mechanisms act to maintain extracellular K+ within a tight window. Through hormonal regulation and direct K+ sensing, the nephron is ideally suited to respond to wide shifts in external K+ balance. Current evidence indicates that dietary K+ loading triggers a coordinated kaliuretic response that appears to involve voltage-dependent changes in sodium transport across multiple nephron segments, including the proximal tubule, medullary loop of Henle, and distal tubule. Inhibition of sodium transport in these segments would accomplish the final goal of enhancing distal NaCl delivery, luminal flow, and K+ secretion in the aldosterone sensitive distal nephron (ASDN). Ongoing research seeks to define the relationship between potassium and volume homeostasis by elucidating pathways that couple renal K+ sensing and tubular function during the potassium stress response.

A human intermediate conductance calcium-activated potassium channel

PubMed Central

Ishii, Takahiro M.; Silvia, Christopher; Hirschberg, Birgit; Bond, Chris T.; Adelman, John P.; Maylie, James

1997-01-01

An intermediate conductance calcium-activated potassium channel, hIK1, was cloned from human pancreas. The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is ≈50% conserved. hIK1 mRNA was detected in peripheral tissues but not in brain. Expression of hIK1 in Xenopus oocytes gave rise to inwardly rectifying potassium currents, which were activated by submicromolar concentrations of intracellular calcium (K0.5 = 0.3 μM). Although the K0.5 for calcium was similar to that of small conductance calcium-activated potassium channels, the slope factor derived from the Hill equation was significantly reduced (1.7 vs. 3.5). Single-channel current amplitudes reflected the macroscopic inward rectification and revealed a conductance level of 39 pS in the inward direction. hIK1 currents were reversibly blocked by charybdotoxin (Ki = 2.5 nM) and clotrimazole (Ki = 24.8 nM) but were minimally affected by apamin (100 nM), iberiotoxin (50 nM), or ketoconazole (10 μM). These biophysical and pharmacological properties are consistent with native intermediate conductance calcium-activated potassium channels, including the erythrocyte Gardos channel. PMID:9326665

[Voltage-gated potassium channels and human neurological diseases].

PubMed

Jin, Hong-Wei; Wang, Xiao-Liang

2002-01-01

Voltage-gated potassium channels (Kv) is the largest, most complex in potassium channel superfamily. It can be divided into Kv alpha subunit and auxiliary two groups. The roles of some Kv channels types, e.g. rapidly inactivating (A-Type channel) and muscarine sensitive channels (M-type channel) are beginning to be understood. They are prominent in nervous system, acting in delicate and accurate ways to control or modify many physiological and pathological functions including membrane excitability, neurotransmitter release, cell proliferation or degeneration, signal transduction in neuronal network. Many human neurological disease pathogenesis are found to be related to mutant of Kv-channels subunit or subtype, such as, learning and memory impairing, ataxia, epilepsy, deafness, etc.

Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride

PubMed Central

Terker, Andrew S.; Zhang, Chong; McCormick, James A.; Lazelle, Rebecca A.; Zhang, Chengbiao; Meermeier, Nicholas P.; Siler, Dominic A.; Park, Hae J.; Fu, Yi; Cohen, David M.; Weinstein, Alan M.; Wang, Wen-Hui; Yang, Chao-Ling; Ellison, David H.

2015-01-01

SUMMARY Dietary potassium deficiency, common in Western diets, raises blood pressure and enhances salt sensitivity. Potassium homeostasis requires a molecular switch in the distal convoluted tubule (DCT), which fails in familial hyperkalemic hypertension (pseudohypoaldosteronism type 2), activating the thiazide-sensitive NaCl cotransporter, NCC. Here, we show that dietary potassium deficiency activates NCC, even in the setting of high salt intake, thereby causing sodium retention and a rise in blood pressure. The effect is dependent on plasma potassium, which modulates DCT cell membrane voltage and, in turn, intracellular chloride. Low intracellular chloride stimulates WNK kinases to activate NCC, limiting potassium losses, even at the expense of increased blood pressure. These data show that DCT cells, like adrenal cells, sense potassium via membrane voltage. In the DCT, hyperpolarization activates NCC via WNK kinases, whereas in the adrenal gland, it inhibits aldosterone secretion. These effects work in concert to maintain potassium homeostasis. PMID:25565204

[Risk for hyperkalemia during long-term treatment with angiotensin-converting enzyme inhibitors in insulin-dependent type 2 diabetics in relation to the glomerular filtration rate].

PubMed

Raml, A; Schmekal, B; Grafinger, P; Biesenbach, G

2001-11-23

The risk for hyperkalaemia during therapy with angiotensin-converting enzyme inhibitors is especially increased in the elderly diabetic because of a decrease in glomerular filtration rate (GFR), as well as the occurrence of hyporeninaemic hypoaldosteronism. We evaluated the risk for hyperkalaemia under long-term angiotensin-converting enyzme inhibition in 86 insulin-dependent type 2 diabetic patients in relation to their GFR. We compared the influence of a 3 to 6 months long treatment with angiotensin-converting enzyme inhibitors on the serum potassium levels, the creatinine clearance and the urinary albumin excretion in insulin-dependent type 2 diabetic patients with an initial creatinine clearance < 50 ml/min/1.73m(2) (n = 15, age 66 +/- 6 years) and >/= 50 ml/min/1.73m(2) respectively (n = 71, age 61 +/- 10 years). In addition, we also investigated the influence on the metabolic control and the blood pressure values in both groups of patients. In the patients with creatinine clearance >/= 50 ml/min/1,73m(2) the mean potassium level increased from 4.3 +/- 0.2 to 4.6 +/- 0.4 mmol/l (P < 0,01), while the incidence of a potassium level > 5 mmol/l was 17 %. In the group with a creatinine clearance < 50 ml/min/1.73m(2) the potassium level rose from 4.5 +/- 0.2 to 5.0 +/- 0.4 mmol/l (P < 0.01). The incidence of potassium levels > 5 mmol/l was 66 % (P < 0,01). In both patient groups the creatinine clearances did not change significantly during angiotensin-converting enzyme inhibition, and the urinary albumin excretion as well as the HbA(1c) values and blood pressure showed only a tendency towards a decrease. Long-term treatment with angiotensin-converting enzyme inhibitors in insulin-dependent type 2 diabetic patients leads to a significant increase in serum potassium. The incidence of hyperkalaemia with potassium levels > 5 mmol/l is significantly higher in the patients with initial creatinine clearance < 50 ml/min/1.73m(2). Severe hyperkalaemia with potassium levels > 6 mmol/l was not observed.

Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation

PubMed Central

Conti, Luca; Renhorn, Jakob; Gabrielsson, Anders; Turesson, Fredrik; Liin, Sara I; Lindahl, Erik; Elinder, Fredrik

2016-01-01

Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions – a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd2+ bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K+ coordination, a hallmark for C-type inactivation. An engineered Cd2+ bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel. PMID:27278891

Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation

NASA Astrophysics Data System (ADS)

Conti, Luca; Renhorn, Jakob; Gabrielsson, Anders; Turesson, Fredrik; Liin, Sara I.; Lindahl, Erik; Elinder, Fredrik

2016-06-01

Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions - a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd2+ bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K+ coordination, a hallmark for C-type inactivation. An engineered Cd2+ bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel.

MinK-dependent internalization of the IKs potassium channel.

PubMed

Xu, Xianghua; Kanda, Vikram A; Choi, Eun; Panaghie, Gianina; Roepke, Torsten K; Gaeta, Stephen A; Christini, David J; Lerner, Daniel J; Abbott, Geoffrey W

2009-06-01

KCNQ1-MinK potassium channel complexes (4alpha:2beta stoichiometry) generate IKs, the slowly activating human cardiac ventricular repolarization current. The MinK ancillary subunit slows KCNQ1 activation, eliminates its inactivation, and increases its unitary conductance. However, KCNQ1 transcripts outnumber MinK transcripts five to one in human ventricles, suggesting KCNQ1 also forms other heteromeric or even homomeric channels there. Mechanisms governing which channel types prevail have not previously been reported, despite their significance: normal cardiac rhythm requires tight control of IKs density and kinetics, and inherited mutations in KCNQ1 and MinK can cause ventricular fibrillation and sudden death. Here, we describe a novel mechanism for this control. Whole-cell patch-clamping, confocal immunofluorescence microscopy, antibody feeding, biotin feeding, fluorescent transferrin feeding, and protein biochemistry techniques were applied to COS-7 cells heterologously expressing KCNQ1 with wild-type or mutant MinK and dynamin 2 and to native IKs channels in guinea-pig myocytes. KCNQ1-MinK complexes, but not homomeric KCNQ1 channels, were found to undergo clathrin- and dynamin 2-dependent internalization (DDI). Three sites on the MinK intracellular C-terminus were, in concert, necessary and sufficient for DDI. Gating kinetics and sensitivity to XE991 indicated that DDI decreased cell-surface KCNQ1-MinK channels relative to homomeric KCNQ1, decreasing whole-cell current but increasing net activation rate; inhibiting DDI did the reverse. The data redefine MinK as an endocytic chaperone for KCNQ1 and present a dynamic mechanism for controlling net surface Kv channel subunit composition-and thus current density and gating kinetics-that may also apply to other alpha-beta type Kv channel complexes.

A new mode of regulation of N-type inactivation in a Caenorhabditis elegans voltage-gated potassium channel.

PubMed

Cai, Shi-Qing; Sesti, Federico

2007-06-22

N-type inactivation in voltage-gated K+ (Kv) channels is a widespread means to modulate neuronal excitability and signaling. Here we have shown a novel mechanism of N-type inactivation in a Caenorhabditis elegans Kv channel. The N-terminal sequence of KVS-1 contains a domain of 22 amino acids that resembles the inactivation ball in A-type channels, which is preceded by a domain of eighteen amino acids. Wild type KVS-1 currents can be described as A-type; however, their kinetics are significantly (approximately 5-fold) slower. When the putative inactivation ball is deleted, the current becomes non-inactivating. Inactivation is restored in non-inactivating channels by diffusion of the missing inactivation domain in the cytoplasm. Deletion of the domain in front of the ball speeds inactivation kinetics approximately 5-fold. We conclude that KVS-1 is the first example of a novel type of Kv channel simultaneously possessing an N-inactivating ball preceded by an N inactivation regulatory domain (NIRD) that acts to slow down inactivation through steric mechanisms.

Activators of potassium M currents have anticonvulsant actions in two rat models of encephalitis

PubMed Central

Solbrig, Marylou V.; Adrian, Russell; Wechsler, Steven L.; Koob, George F.

2010-01-01

Opioid systems in hippocampus regulate excitability and kappa opioids have a role in anticonvulsant protection, but their mechanisms of action are incompletely understood. We examined the ability of opioid and nonopioid agents with overlapping ionic mechanisms and actions similar to kappa opioid agonists, to block seizures in rat models of encephalitis due to Borna Disease virus and Herpes Simplex Virus Type-1. Naltrindole, a delta antagonist and thus a kappa opioid sparing agent, (10 mg/kg s.c.) blocked spontaneous and naloxone (opioid antagonist)-induced seizures in the models, but produced somatic signs similar to opioid withdrawal. Given that delta antagonists as well as kappa opioid agonists in hippocampus enhance potassium M currents (IM), we tested the effect of the IM augmenter flupirtine. Flupirtine (20 mg/kg i.p.) prevented seizures in Borna and herpes infected rats, without signs of withdrawal, hypotonia or sedation. The results support the efficacy of opioid and nonopioid drugs in modulating naloxone-induced seizures in critical illness due to viral encephalitis and by analogy, opioid withdrawal seizures. PMID:17126318

Neuronal Atrophy Early in Degenerative Ataxia Is a Compensatory Mechanism to Regulate Membrane Excitability

PubMed Central

Dell'Orco, James M.; Wasserman, Aaron H.; Chopra, Ravi; Ingram, Melissa A. C.; Hu, Yuan-Shih; Singh, Vikrant; Wulff, Heike; Opal, Puneet; Orr, Harry T.

2015-01-01

Neuronal atrophy in neurodegenerative diseases is commonly viewed as an early event in a continuum that ultimately results in neuronal loss. In a mouse model of the polyglutamine disorder spinocerebellar ataxia type 1 (SCA1), we tested the hypothesis that cerebellar Purkinje neuron atrophy serves an adaptive role rather than being simply a nonspecific response to injury. In acute cerebellar slices from SCA1 mice, we find that Purkinje neuron pacemaker firing is initially normal but, with the onset of motor dysfunction, becomes disrupted, accompanied by abnormal depolarization. Remarkably, subsequent Purkinje cell atrophy is associated with a restoration of pacemaker firing. The early inability of Purkinje neurons to support repetitive spiking is due to unopposed calcium currents resulting from a reduction in large-conductance calcium-activated potassium (BK) and subthreshold-activated potassium channels. The subsequent restoration of SCA1 Purkinje neuron firing correlates with the recovery of the density of these potassium channels that accompanies cell atrophy. Supporting a critical role for BK channels, viral-mediated increases in BK channel expression in SCA1 Purkinje neurons improves motor dysfunction and partially restores Purkinje neuron morphology. Cerebellar perfusion of flufenamic acid, an agent that restores the depolarized membrane potential of SCA1 Purkinje neurons by activating potassium channels, prevents Purkinje neuron dendritic atrophy. These results suggest that Purkinje neuron dendritic remodeling in ataxia is an adaptive response to increases in intrinsic membrane excitability. Similar adaptive remodeling could apply to other vulnerable neuronal populations in neurodegenerative disease. SIGNIFICANCE STATEMENT In neurodegenerative disease, neuronal atrophy has long been assumed to be an early nonspecific event preceding neuronal loss. However, in a mouse model of spinocerebellar ataxia type 1 (SCA1), we identify a previously unappreciated compensatory role for neuronal shrinkage. Purkinje neuron firing in these mice is initially normal, but is followed by abnormal membrane depolarization resulting from a reduction in potassium channels. Subsequently, these electrophysiological effects are counteracted by cell atrophy, which by restoring normal potassium channel membrane density, re-establishes pacemaker firing. Reversing the initial membrane depolarization improved motor function and Purkinje neuron morphology in the SCA1 mice. These results suggest that Purkinje neuron remodeling in ataxia is an active compensatory response that serves to normalize intrinsic membrane excitability. PMID:26269637

Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

PubMed Central

Liu, Pin W.

2014-01-01

Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

Potassium measurements and risk of type 2 diabetes: a dose-response meta-analysis of prospective cohort studies

PubMed Central

Peng, Yang; Zhong, Guo-Chao; Mi, Qiao; Li, Kejia; Wang, Ao; Li, Ling; Liu, Hua; Yang, Gangyi

2017-01-01

Objective To clarify the relationship between serum, dietary, and urinary potassium and the risk of type 2 diabetes mellitus (T2DM). Materials and Methods We searched PubMed and EMBASE through January 6, 2017 for studies reporting risk estimates on the association of potassium measurements and the risk of T2DM. The summary risk estimates were obtained through a random-effects model. Dose-response analysis was conducted. Results Eight studies involving 5,053 cases and 119,993 individuals were included. A trend toward significance was found in the highest versus lowest meta-analysis on serum potassium and T2DM risk (RR = 0.79; 95% CI 0.60–1.04); moreover, the RR per 1 mmol/L increase in serum potassium was 0.83 (95% CI 0.73–0.95). A non-significant association of dietary potassium and T2DM risk was detected (RR for the highest versus lowest category: 0.93; 95% CI 0.81–1.06; RR for every 1000mg increase per day: 1.00, 95% CI 0.96–1.05). A similar non-significant association was found for urinary potassium and T2DM risk (RR for the highest versus lowest category: 0.83; 95% CI 0.39–1.75; RR per 10 mmol increase: 1.00; 95% CI 0.95–1.05). Evidence of a linear association between serum, dietary, and urinary potassium and the risk of T2DM was found (all Pnon-linearity > 0.05). Conclusions Low serum potassium increases the risk of T2DM in a linear dose-response manner; nevertheless, neither dietary potassium nor urinary potassium shows any association with the risk of T2DM. However, these findings should be interpreted with caution due to limited studies. PMID:29246005

Urinary Potassium Excretion and Renal and Cardiovascular Complications in Patients with Type 2 Diabetes and Normal Renal Function

PubMed Central

Haneda, Masakazu; Koya, Daisuke; Kondo, Keiko; Tanaka, Sachiko; Arima, Hisatomi; Kume, Shinji; Nakazawa, Jun; Chin-Kanasaki, Masami; Ugi, Satoshi; Kawai, Hiromichi; Araki, Hisazumi; Uzu, Takashi; Maegawa, Hiroshi

2015-01-01

Background and objectives We investigated the association of urinary potassium and sodium excretion with the incidence of renal failure and cardiovascular disease in patients with type 2 diabetes. Design, setting, participants, & measurements A total of 623 Japanese type 2 diabetic patients with eGFR≥60 ml/min per 1.73 m2 were enrolled in this observational follow-up study between 1996 and 2003 and followed-up until 2013. At baseline, a 24-hour urine sample was collected to estimate urinary potassium and sodium excretion. The primary end point was renal and cardiovascular events (RRT, myocardial infarction, angina pectoris, stroke, and peripheral vascular disease). The secondary renal end points were the incidence of a 50% decline in eGFR, progression to CKD stage 4 (eGFR<30 ml/min per 1.73 m2), and the annual decline rate in eGFR. Results During the 11-year median follow-up period, 134 primary end points occurred. Higher urinary potassium excretion was associated with lower risk of the primary end point, whereas urinary sodium excretion was not. The adjusted hazard ratios for the primary end point in Cox proportional hazards analysis were 0.56 (95% confidence interval [95% CI], 0.33 to 0.95) in the third quartile of urinary potassium excretion (2.33–2.90 g/d) and 0.33 (95% CI, 0.18 to 0.62) in the fourth quartile (>2.90 g/d) compared with the lowest quartile (<1.72 g/d). Similar associations were observed for the secondary renal end points. The annual decline rate in eGFR in the fourth quartile of urinary potassium excretion (–1.3 ml/min per 1.73 m2/y; 95% CI, –1.5 to –1.0) was significantly slower than those in the first quartile (–2.2; 95% CI, –2.4 to –1.8). Conclusions Higher urinary potassium excretion was associated with the slower decline of renal function and the lower incidence of cardiovascular complications in type 2 diabetic patients with normal renal function. Interventional trials are necessary to determine whether increasing dietary potassium is beneficial. PMID:26563378

The inhibitory effects of potassium chloride versus potassium silicate application on (137)Cs uptake by rice.

PubMed

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.

Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Birinyi-Strachan, Liesl C.; Gunning, Simon J.; Lewis, Richard J.

2005-04-15

The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Na{sub v}) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Na{sub v} channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons,more » P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Na{sub v} currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Na{sub v} channel gating, observed clinically in response to ciguatera poisoning.« less

Potassium intake modulates the thiazide-sensitive sodium-chloride cotransporter (NCC) activity via the Kir4.1 potassium channel.

PubMed

Wang, Ming-Xiao; Cuevas, Catherina A; Su, Xiao-Tong; Wu, Peng; Gao, Zhong-Xiuzi; Lin, Dao-Hong; McCormick, James A; Yang, Chao-Ling; Wang, Wen-Hui; Ellison, David H

2018-04-01

Kir4.1 in the distal convoluted tubule plays a key role in sensing plasma potassium and in modulating the thiazide-sensitive sodium-chloride cotransporter (NCC). Here we tested whether dietary potassium intake modulates Kir4.1 and whether this is essential for mediating the effect of potassium diet on NCC. High potassium intake inhibited the basolateral 40 pS potassium channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule, decreased basolateral potassium conductance, and depolarized the distal convoluted tubule membrane in Kcnj10flox/flox mice, herein referred to as control mice. In contrast, low potassium intake activated Kir4.1, increased potassium currents, and hyperpolarized the distal convoluted tubule membrane. These effects of dietary potassium intake on the basolateral potassium conductance and membrane potential in the distal convoluted tubule were completely absent in inducible kidney-specific Kir4.1 knockout mice. Furthermore, high potassium intake decreased, whereas low potassium intake increased the abundance of NCC expression only in the control but not in kidney-specific Kir4.1 knockout mice. Renal clearance studies demonstrated that low potassium augmented, while high potassium diminished, hydrochlorothiazide-induced natriuresis in control mice. Disruption of Kir4.1 significantly increased basal urinary sodium excretion but it abolished the natriuretic effect of hydrochlorothiazide. Finally, hypokalemia and metabolic alkalosis in kidney-specific Kir4.1 knockout mice were exacerbated by potassium restriction and only partially corrected by a high-potassium diet. Thus, Kir4.1 plays an essential role in mediating the effect of dietary potassium intake on NCC activity and potassium homeostasis. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain.

PubMed

Rhodes, Kenneth J; Carroll, Karen I; Sung, M Amy; Doliveira, Lisa C; Monaghan, Michael M; Burke, Sharon L; Strassle, Brian W; Buchwalder, Lynn; Menegola, Milena; Cao, Jie; An, W Frank; Trimmer, James S

2004-09-08

Voltage-gated potassium (Kv) channels from the Kv4, or Shal-related, gene family underlie a major component of the A-type potassium current in mammalian central neurons. We recently identified a family of calcium-binding proteins, termed KChIPs (Kv channel interacting proteins), that bind to the cytoplasmic N termini of Kv4 family alpha subunits and modulate their surface density, inactivation kinetics, and rate of recovery from inactivation (An et al., 2000). Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs1-4 and Kv4 family alpha subunits in adult rat brain. Immunohistochemical staining using KChIP-specific monoclonal antibodies revealed that the KChIP polypeptides are concentrated in neuronal somata and dendrites where their cellular and subcellular distribution overlaps, in an isoform-specific manner, with that of Kv4.2 and Kv4.3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons. Immunoreactivity for KChIP2, KChIP4, and Kv4.2 is concentrated in the apical and basal dendrites of hippocampal and neocortical pyramidal cells. Double-label immunofluorescence labeling revealed that throughout the forebrain, KChIP2 and KChIP4 are frequently colocalized with Kv4.2, whereas in cortical, hippocampal, and striatal interneurons, KChIP1 is frequently colocalized with Kv4.3. Coimmunoprecipitation analyses confirmed that all KChIPs coassociate with Kv4 alpha subunits in brain membranes, indicating that KChIPs 1-4 are integral components of native A-type Kv channel complexes and are likely to play a major role as modulators of somatodendritic excitability.

Differential Expression of Inward and Outward Potassium Currents in the Macrophage-like Cell Line J774.1

DTIC Science & Technology

1985-04-02

skeletal muscle (Adrian, Hodgkin & Chandler, 1970), and nerve (Goldman & Schauf , 1973; Thompson, 1977). The general mathematical formalism describes the...594-609. Goldman, L. & Schauf , C. L. (1973) Quantitative description of sodium and potassium currents and computed action potentials in Myxicola giant

Rapid communication between neurons and astrocytes in primary cortical cultures.

PubMed

Murphy, T H; Blatter, L A; Wier, W G; Baraban, J M

1993-06-01

The identification of neurotransmitter receptors and voltage-sensitive ion channels on astrocytes (reviewed by Barres, 1991) has renewed interest in how these cells respond to neuronal activity. To investigate the physiology of neuron astrocyte signaling, we have employed primary cortical cultures that contain both neuronal and glial cells. As the neurons in these cultures exhibit synchronous spontaneous synaptic activity, we have used both calcium imaging and whole-cell recording techniques to identify physiological activity in astrocytes related to neuronal activity. Whole-cell voltage-clamp records from astrocytes revealed rapid inward currents that coincide with bursts of electrical activity in neighboring neurons. Calcium imaging studies demonstrate that these currents in astrocytes are not always associated with slowly propagating calcium waves. Inclusion of the dye Lucifer yellow within patch pipettes confirmed that astrocytes are extensively coupled to each other but not to adjacent neurons, indicating that the currents observed are not due to gap junction connections between these cell types. These currents do not reflect widespread diffusion of glutamate or potassium released during neuronal activity since a population of small, round, multipolar presumed glial cells that are not dye coupled to adjacent cells did not display electrical currents coincident with neuronal firing, even though they respond to locally applied glutamate and potassium. These findings indicate that, in addition to the relatively slow signaling conveyed by calcium waves, astrocytes also display rapid electrical responses to neuronal activity.

CNS Schwann cells display oligodendrocyte precursor-like potassium channel activation and antigenic expression in vitro.

PubMed

Kegler, Kristel; Imbschweiler, Ilka; Ulrich, Reiner; Kovermann, Peter; Fahlke, Christoph; Deschl, Ulrich; Kalkuhl, Arno; Baumgärnter, Wolfgang; Wewetzer, Konstantin

2014-06-01

Central nervous system (CNS) injury triggers production of myelinating Schwann cells from endogenous oligodendrocyte precursors (OLPs). These CNS Schwann cells may be attractive candidates for novel therapeutic strategies aiming to promote endogenous CNS repair. However, CNS Schwann cells have been so far mainly characterized in situ regarding morphology and marker expression, and it has remained enigmatic whether they display functional properties distinct from peripheral nervous system (PNS) Schwann cells. Potassium channels (K+) have been implicated in progenitor and glial cell proliferation after injury and may, therefore, represent a suitable pharmacological target. In the present study, we focused on the function and expression of voltage-gated K+ channels Kv(1-12) and accessory β-subunits in purified adult canine CNS and PNS Schwann cell cultures using electrophysiology and microarray analysis and characterized their antigenic phenotype. We show here that K+ channels differed significantly in both cell types. While CNS Schwann cells displayed prominent K D-mediated K+ currents, PNS Schwann cells elicited K(D-) and K(A-type) K+ currents. Inhibition of K+ currents by TEA and Ba2+ was more effective in CNS Schwann cells. These functional differences were not paralleled by differential mRNA expression of Kv(1-12) and accessory β-subunits. However, O4/A2B5 and GFAP expressions were significantly higher and lower, respectively, in CNS than in PNS Schwann cells. Taken together, this is the first evidence that CNS Schwann cells display specific properties not shared by their peripheral counterpart. Both Kv currents and increased O4/A2B5 expression were reminiscent of OLPs suggesting that CNS Schwann cells retain OLP features during maturation.

Serum potassium level and dietary potassium intake as risk factors for stroke.

PubMed

Green, D M; Ropper, A H; Kronmal, R A; Psaty, B M; Burke, G L

2002-08-13

Numerous studies have found that low potassium intake and low serum potassium are associated with increased stroke mortality, but data regarding stroke incidence have been limited. Serum potassium levels, dietary potassium intake, and diuretic use in relation to risk for stroke in a prospectively studied cohort were investigated. The study comprised 5,600 men and women older than 65 years who were free of stroke at enrollment. Baseline data included serum potassium level, dietary potassium intake, and diuretic use. Participants were followed for 4 to 8 years, and the incidence and types of strokes were recorded. Low serum potassium was defined as less than 4.1 mEq/L, and low potassium intake as less than 2.4 g/d. Among diuretic users, there was an increased risk for stroke associated with lower serum potassium (relative risk [RR]: 2.5, p < 0.0001). Among individuals not taking diuretics, there was an increased risk for stroke associated with low dietary potassium intake (RR: 1.5, p < 0.005). The small number of diuretic users with lower serum potassium and atrial fibrillation had a 10-fold greater risk for stroke compared with those with higher serum potassium and normal sinus rhythm. A lower serum potassium level in diuretic users, and low potassium intake in those not taking diuretics were associated with increased stroke incidence among older individuals. Lower serum potassium was associated with a particularly high risk for stroke in the small number of diuretic users with atrial fibrillation. Further study is required to determine if modification of these factors would prevent strokes.

Diminished A-type potassium current and altered firing properties in presympathetic PVN neurones in renovascular hypertensive rats

PubMed Central

Sonner, Patrick M; Filosa, Jessica A; Stern, Javier E

2008-01-01

Accumulating evidence supports a contribution of the hypothalamic paraventricular nucleus (PVN) to sympathoexcitation and elevated blood pressure in renovascular hypertension. However, the underlying mechanisms resulting in altered neuronal function in hypertensive rats remain largely unknown. Here, we aimed to address whether the transient outward potassium current (IA) in identified rostral ventrolateral medulla (RVLM)-projecting PVN neurones is altered in hypertensive rats, and whether such changes affected single and repetitive action potential properties and associated changes in intracellular Ca2+ levels. Patch-clamp recordings obtained from PVN-RVLM neurons showed a reduction in IA current magnitude and single channel conductance, and an enhanced steady-state current inactivation in hypertensive rats. Morphometric reconstructions of intracellularly labelled PVN-RVLM neurons showed a diminished dendritic surface area in hypertensive rats. Consistent with a diminished IA availability, action potentials in PVN-RVLM neurons in hypertensive rats were broader, decayed more slowly, and were less sensitive to the K+ channel blocker 4-aminopyridine. Simultaneous patch clamp recordings and confocal Ca2+ imaging demonstrated enhanced action potential-evoked intracellular Ca2+ transients in hypertensive rats. Finally, spike broadening during repetitive firing discharge was enhanced in PVN-RVLM neurons from hypertensive rats. Altogether, our results indicate that diminished IA availability constitutes a contributing mechanism underlying aberrant central neuronal function in renovascular hypertension. PMID:18238809

Adenosine Triphosphate (ATP) Inhibits Voltage-Sensitive Potassium Currents in Isolated Hensen's Cells and Nifedipine Protects Against Noise-Induced Hearing Loss in Guinea Pigs.

PubMed

Ye, Rui; Liu, Jun; Jia, Zhiying; Wang, Hongyang; Wang, YongAn; Sun, Wei; Wu, Xuan; Zhao, Zhifei; Niu, Baolong; Li, Xingqi; Dai, Guanghai; Li, Jianxiong

2016-06-13

BACKGROUND There is increasing evidence that adenosine triphosphate (ATP), a well-known neurotransmitter and neuromodulator in the central nervous system, plays an important role as an extracellular chemical messenger in the cochlea. MATERIAL AND METHODS Using a whole-cell recording technique, we studied the effects of ATP on isolated Hensen's cells, which are supporting cells in the cochlea, to determine if they are involved in the transduction of ions with hair cells. RESULTS ATP (0.1-10 µM) reduced the potassium current (IK+) in the majority of the recorded Hensen's cells (21 out of 25 cells). An inward current was also induced by high concentrations of ATP (100 µM to 10 mM), which was reversibly blocked by 100 µM suramin (a purinergic antagonist) and blocked by nifedipine (an L-type calcium channel blocker). After the cochleas were perfused with artificial perilymph solutions containing nifedipine and exposed to noise, the amplitude increase in the compound action potential (CAP) threshold and the reduction in cochlear microphonics was lower than when they were exposed to noise alone. CONCLUSIONS Our results suggest that ATP can block IK+ channels at a low concentration and induce an inward Ca2+ current at high concentrations, which is reversed by purinergic receptors. Nifedipine may have a partially protective effect on noise-induced hearing loss (NIHL).

Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride.

PubMed

Terker, Andrew S; Zhang, Chong; McCormick, James A; Lazelle, Rebecca A; Zhang, Chengbiao; Meermeier, Nicholas P; Siler, Dominic A; Park, Hae J; Fu, Yi; Cohen, David M; Weinstein, Alan M; Wang, Wen-Hui; Yang, Chao-Ling; Ellison, David H

2015-01-06

Dietary potassium deficiency, common in modern diets, raises blood pressure and enhances salt sensitivity. Potassium homeostasis requires a molecular switch in the distal convoluted tubule (DCT), which fails in familial hyperkalemic hypertension (pseudohypoaldosteronism type 2), activating the thiazide-sensitive NaCl cotransporter, NCC. Here, we show that dietary potassium deficiency activates NCC, even in the setting of high salt intake, thereby causing sodium retention and a rise in blood pressure. The effect is dependent on plasma potassium, which modulates DCT cell membrane voltage and, in turn, intracellular chloride. Low intracellular chloride stimulates WNK kinases to activate NCC, limiting potassium losses, even at the expense of increased blood pressure. These data show that DCT cells, like adrenal cells, sense potassium via membrane voltage. In the DCT, hyperpolarization activates NCC via WNK kinases, whereas in the adrenal gland, it inhibits aldosterone secretion. These effects work in concert to maintain potassium homeostasis. Copyright © 2015 Elsevier Inc. All rights reserved.

Gitelman or Bartter type 3 syndrome? A case of distal convoluted tubulopathy caused by CLCNKB gene mutation

PubMed Central

Cruz, António José; Castro, Alexandra

2013-01-01

A 32-year-old woman with no significant medical history was sent to our consultation due to hypokalaemia (<3.0 mmol/l). Her main complaints were longstanding polyuria and nocturia. Physical examination was normal. Basic investigations showed normal renal function, low serum potassium (2.7 mmol/l) and magnesium (0.79 mmol/l), metabolic alkalosis (pH 7.54; bicarbonate 32.5 mmol/l), elevated urinary potassium (185 mmol/24 h) and normal urinary calcium (246 mg/24 h). Thiazide test revealed blunted response. Chronic vomiting and the abuse of diuretics were excluded. Genetic tests for SLC12A3 gene mutation described in Gitelman syndrome (GS) came negative. CLCNKB gene mutation analysis present in both GS and Bartter (BS) type 3 syndromes was positive. The patient is now being treated with potassium and magnesium oral supplements, ramipril and spironolactone with stable near-normal potassium and magnesium levels. This article presents the case of a patient with hypokalaemia caused by CLCNKB gene mutation hard to categorise as GS or BS type 3. PMID:23345488

Gitelman or Bartter type 3 syndrome? A case of distal convoluted tubulopathy caused by CLCNKB gene mutation.

PubMed

Cruz, António José; Castro, Alexandra

2013-01-22

A 32-year-old woman with no significant medical history was sent to our consultation due to hypokalaemia (<3.0 mmol/l). Her main complaints were longstanding polyuria and nocturia. Physical examination was normal. Basic investigations showed normal renal function, low serum potassium (2.7 mmol/l) and magnesium (0.79 mmol/l), metabolic alkalosis (pH 7.54; bicarbonate 32.5 mmol/l), elevated urinary potassium (185 mmol/24 h) and normal urinary calcium (246 mg/24 h). Thiazide test revealed blunted response. Chronic vomiting and the abuse of diuretics were excluded. Genetic tests for SLC12A3 gene mutation described in Gitelman syndrome (GS) came negative. CLCNKB gene mutation analysis present in both GS and Bartter (BS) type 3 syndromes was positive. The patient is now being treated with potassium and magnesium oral supplements, ramipril and spironolactone with stable near-normal potassium and magnesium levels. This article presents the case of a patient with hypokalaemia caused by CLCNKB gene mutation hard to categorise as GS or BS type 3.

An electrophysiological study on the effects of Pa-1G (a phospholipase A(2)) from the venom of king brown snake, Pseudechis australis, on neuromuscular function.

PubMed

Fatehi, M; Rowan, E G; Harvey, A L

2002-01-01

The effects of Pa-1G, a phospholipase A(2) (PLA(2)) from the venom of the Australian king brown snake (Pseudechis australis) were determined on the release of acetylcholine, muscle resting membrane potential and motor nerve terminal action potential at mouse neuromuscular junction. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations revealed that Pa-1G (800 nM) significantly reduced the amplitude of endplate potentials within 10 min exposure. The quantal content of endplate potentials was decreased to 58+/-6% of control after 30 min exposure to 800 nM Pa-1G. The toxin also caused a partial depolarisation of mouse muscle fibres within 60 min exposure. Extracellular recording of action potentials at motor nerve terminals showed that Pa-1G reduced the waveforms associated with both sodium and potassium conductances. To investigate whether this was a direct or indirect effect of the toxin on these ionic currents, whole cell patch clamp experiments were performed using human neuroblastoma (SK-N-SH) cells and B82 mouse fibroblasts stably transfected with rKv1.2. Patch clamp recording experiments confirmed that potassium currents sensitive to alpha-dendrotoxin recorded from B82 cells and sodium currents in SK-N-SH cells were not affected by the toxin. Since neither facilitation of acetylcholine release at mouse neuromuscular junction nor depression of potassium currents in B82 cells has been observed, the apparent blockade of potassium currents at mouse motor nerve endings induced by the toxin is unlikely to be due to a selective block of potassium channels.

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

PubMed

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.

Potassium Currents of Olfactory Bulb Juxtaglomerular Cells: Characterization, Simulation, and Implications for Plateau Potential Firing

PubMed Central

Masurkar, Arjun V.; Chen, Wei R.

2011-01-01

Odor identity is encoded by the activity of olfactory bulb glomeruli, which receive primary sensory input and transfer it to projection neurons. Juxtaglomerular cells (JGCs) may influence glomerular processing via firing of long lasting plateau potentials. Though inward currents have been investigated, little is known regarding potassium current contribution to JGC plateau potentials. We pursued study of these currents, with the overarching goal of creating components for a computational model of JGC plateau potential firing. In conditions minimizing calcium-activated potassium current (IK(Ca)), we used whole cell voltage clamp and in vitro slice preparations to characterize three potassium currents in rat JGCs. The prominent component Ikt1 displayed rapid kinetics (τ10%−90% rise 0.6–2ms, τinactivation 5–10ms) and was blocked by high concentration 4-AP (5mM) and TEA (40mM). It had half maximal activation at −10mV (V½max) and little inactivation at rest. Ikt2, with slower kinetics (τ10%−90% rise 11–15ms, τinactivation 100–300ms), was blocked by low concentration 4-AP (0.5mM) and TEA (5mM). The V½max was 0mV and inactivation was also minimal at rest. Sustained current Ikt3 showed sensitivity to low concentration 4-AP and TEA, and had V½max of +10mV. Further experiments, in conditions of physiologic calcium buffering, suggested that IK(Ca) contributed to Ikt3 with minimal effect on plateau potential evolution. We transformed these characterizations into Hodgkin-Huxley models that robustly mimicked experimental data. Further simulation demonstrated that Ikt1 would be most efficiently activated by plateau potential waveforms, predicting a critical role in shaping JGC firing. These studies demonstrated that JGCs possess a unique potassium current profile, with delayed rectifier (Ikt3), atypical A-current (Ikt1), and D-current (Ikt2) in accordance with known expression patterns in OB glomeruli. Our simulations also provide an initial framework for more integrative models of JGC plateau potential firing. PMID:21704678

Kv1 channels and neural processing in vestibular calyx afferents.

PubMed

Meredith, Frances L; Kirk, Matthew E; Rennie, Katherine J

2015-01-01

Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K(+) channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K(+) channels could help alleviate vestibular dysfunction on earth and in space.

[Study on teratogenic effect of potassium dichromate on Vicia faba root tip cells].

PubMed

Qian, Xiao-Wei

2004-05-01

We studied the aberrant effects of different concentrations of potassium dichromate on Vicia faba root tip cells. The micronucleus and chromosome aberration assay was conducted to determine the micronucleus rate and chromosome aberration rate of Vicia faba root tip cells induced by potassium dichromate. The result indicated that potassium dichromate could increase the micronucleus rate of Vicia faba root tip cells. Within certain range of concentration the rate of micronucleus was found to be increased with the increase of potassium dichromate concentration,but beyond this range the rate of micronucleus decreased with further increase of potassium dichromate concentration. The potassium dichromate at different concentrations could increase the cell mitosis index. Besides,it also caused various types of chromosome aberration,and the rates of chromosome aberration were always higher than that of the control group. The conclusion of this study was that potassium dichromate has obvious teratogenic effect on Vicia faba root tip cells.

Comparison of Chemical Extraction Methods for Determination of Soil Potassium in Different Soil Types

NASA Astrophysics Data System (ADS)

Zebec, V.; Rastija, D.; Lončarić, Z.; Bensa, A.; Popović, B.; Ivezić, V.

2017-12-01

Determining potassium supply of soil plays an important role in intensive crop production, since it is the basis for balancing nutrients and issuing fertilizer recommendations for achieving high and stable yields within economic feasibility. The aim of this study was to compare the different extraction methods of soil potassium from arable horizon of different types of soils with ammonium lactate method (KAL), which is frequently used as analytical method for determining the accessibility of nutrients and it is a common method used for issuing fertilizer recommendations in many Europe countries. In addition to the ammonium lactate method (KAL, pH 3.75), potassium was extracted with ammonium acetate (KAA, pH 7), ammonium acetate ethylenediaminetetraacetic acid (KAAEDTA, pH 4.6), Bray (KBRAY, pH 2.6) and with barium chloride (K_{BaCl_2 }, pH 8.1). The analyzed soils were extremely heterogeneous with a wide range of determined values. Soil pH reaction ( {pH_{H_2 O} } ) ranged from 4.77 to 8.75, organic matter content ranged from 1.87 to 4.94% and clay content from 8.03 to 37.07%. In relation to KAL method as the standard method, K_{BaCl_2 } method extracts 12.9% more on average of soil potassium, while in relation to standard method, on average KAA extracts 5.3%, KAAEDTA 10.3%, and KBRAY 27.5% less of potassium. Comparison of analyzed extraction methods of potassium from the soil is of high precision, and most reliable comparison was KAL method with KAAEDTA, followed by a: KAA, K_{BaCl_2 } and KBRAY method. Extremely significant statistical correlation between different extractive methods for determining potassium in the soil indicates that any of the methods can be used to accurately predict the concentration of potassium in the soil, and that carried out research can be used to create prediction model for concentration of potassium based on different methods of extraction.

Origin of heterogeneous spiking patterns from continuously distributed ion channel densities: a computational study in spinal dorsal horn neurons.

PubMed

Balachandar, Arjun; Prescott, Steven A

2018-05-01

Distinct spiking patterns may arise from qualitative differences in ion channel expression (i.e. when different neurons express distinct ion channels) and/or when quantitative differences in expression levels qualitatively alter the spike generation process. We hypothesized that spiking patterns in neurons of the superficial dorsal horn (SDH) of spinal cord reflect both mechanisms. We reproduced SDH neuron spiking patterns by varying densities of K V 1- and A-type potassium conductances. Plotting the spiking patterns that emerge from different density combinations revealed spiking-pattern regions separated by boundaries (bifurcations). This map suggests that certain spiking pattern combinations occur when the distribution of potassium channel densities straddle boundaries, whereas other spiking patterns reflect distinct patterns of ion channel expression. The former mechanism may explain why certain spiking patterns co-occur in genetically identified neuron types. We also present algorithms to predict spiking pattern proportions from ion channel density distributions, and vice versa. Neurons are often classified by spiking pattern. Yet, some neurons exhibit distinct patterns under subtly different test conditions, which suggests that they operate near an abrupt transition, or bifurcation. A set of such neurons may exhibit heterogeneous spiking patterns not because of qualitative differences in which ion channels they express, but rather because quantitative differences in expression levels cause neurons to operate on opposite sides of a bifurcation. Neurons in the spinal dorsal horn, for example, respond to somatic current injection with patterns that include tonic, single, gap, delayed and reluctant spiking. It is unclear whether these patterns reflect five cell populations (defined by distinct ion channel expression patterns), heterogeneity within a single population, or some combination thereof. We reproduced all five spiking patterns in a computational model by varying the densities of a low-threshold (K V 1-type) potassium conductance and an inactivating (A-type) potassium conductance and found that single, gap, delayed and reluctant spiking arise when the joint probability distribution of those channel densities spans two intersecting bifurcations that divide the parameter space into quadrants, each associated with a different spiking pattern. Tonic spiking likely arises from a separate distribution of potassium channel densities. These results argue in favour of two cell populations, one characterized by tonic spiking and the other by heterogeneous spiking patterns. We present algorithms to predict spiking pattern proportions based on ion channel density distributions and, conversely, to estimate ion channel density distributions based on spiking pattern proportions. The implications for classifying cells based on spiking pattern are discussed. © 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Free RCK arrangement in Kch, a putative escherichia coli potassium channel, as suggested by electron crystallography.

PubMed

Kuang, Qie; Purhonen, Pasi; Jegerschöld, Caroline; Koeck, Philip J B; Hebert, Hans

2015-01-06

The ligand-gated potassium channels are stimulated by various kinds of messengers. Previous studies showed that ligand-gated potassium channels containing RCK domains (the regulator of the conductance of potassium ion) form a dimer of tetramer structure through the RCK octameric gating ring in the presence of detergent. Here, we have analyzed the structure of Kch, a channel of this type from Escherichia coli, in a lipid environment using electron crystallography. By combining information from the 3D map of the transmembrane part of the protein and docking of an atomic model of a potassium channel, we conclude that the RCK domains face the solution and that an RCK octameric gating ring arrangement does not form under our crystallization condition. Our findings may be applied to other potassium channels that have an RCK gating ring arrangement. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

PubMed Central

Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

2012-01-01

Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

Angiotensin II and angiotensin II receptor blocker modulate the arrhythmogenic activity of pulmonary veins.

PubMed

Chen, Yi-Jen; Chen, Yao-Chang; Tai, Ching-Tai; Yeh, Hung-I; Lin, Cheng-I; Chen, Shih-Ann

2006-01-01

Angiotensin II receptor blockers (AIIRBs) have been shown to prevent atrial fibrillation. The pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The aim of this study was to evaluate whether angiotensin II or AIIRB may change the arrhythmogenic activity of the PVs. Conventional microelectrodes and whole-cell patch clamps were used to investigate the action potentials (APs) and ionic currents in isolated rabbit PV tissue and single cardiomyocytes before and after administering angiotensin II or losartan (AIIRB). In the tissue preparations, angiotensin II induced delayed after-depolarizations (1, 10, and 100 nM) and accelerated the automatic rhythm (10 and 100 nM). Angiotensin II (100 nM) prolonged the AP duration and increased the contractile force (10 and 100 nM). Losartan (1 and 10 microM) inhibited the automatic rhythm. Losartan (10 microM) prolonged the AP duration and reduced the contractile force (1 and 10 microM). Angiotensin II reduced the transient outward potassium current (I(to)) but increased the L-type calcium, delayed rectifier potassium (I(K)), transient inward (I(ti)), pacemaker, and Na(+)-Ca(2+) exchanger (NCX) currents in the PV cardiomyocytes. Losartan decreased the I(to), I(K), I(ti), and NCX currents. In conclusion, angiotensin II and AIIRB modulate the PV electrical activity, which may play a role in the pathophysiology of atrial fibrillation.

Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation.

PubMed

Yang, Baode; Li, Chenxing; Sun, Junyi; Wang, Xinghui; Liu, Xinling; Yang, Chun; Chen, Lina; Zhou, Jun; Hu, Hao

2017-05-01

Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5-50.0mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I Kv1.5 ) were markedly inhibited by 12.5-50.0mM ethanol in a concentration-dependent manner. Ethanol with 50.0mM could inhibit rapid delayed rectifier potassium currents (I hERG ). Ethanol under 6.25-50.0mM did not affect on inward rectifier potassium currents (I Kir2.1 ). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I Kv1.5 and I hERG , which contributed to preventing the development and duration of AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Sodium and potassium conductance changes during a membrane action potential

PubMed Central

Bezanilla, Francisco; Rojas, Eduardo; Taylor, Robert E.

1970-01-01

1. A method for turning a membrane potential control system on and off in less than 10 μsec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential. 2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential. 3. The total membrane conductance taken from these current—voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939). 4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin—Huxley equations. 5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential. PMID:5505231

Subdiaphragmatic vagotomy increases the sensitivity of lumbar Aδ primary afferent neurons along with voltage-dependent potassium channels in rats.

PubMed

Furuta, Sadayoshi; Watanabe, Lisa; Doi, Seira; Horiuchi, Hiroshi; Matsumoto, Kenjiro; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru

2012-02-01

Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz, which indicated that lumbar primary afferent Aδ sensitivity was enhanced in SDV rats. The whole-cell patch-clamp technique also revealed the hyper-excitability of acutely dissociated medium-sized lumbar dorsal root ganglion (DRG) neurons isolated from SDV rats. The contribution of changes in voltage-dependent potassium (Kv) channels was assessed, and transient A-type K(+) (I(A) ) current density was apparently decreased. Moreover, Kv4.3 immunoreactivity in medium-sized DRG neurons was significantly reduced in SDV rats compared to sham. These results indicate that SDV causes hyper-excitability of lumbar primary Aδ afferent neurons, which may be induced along with suppressing I(A) currents via the decreased expression of Kv4.3. Thus, peripheral Aδ neuroplasticity may contribute to the chronic lower limb pain caused by SDV. Copyright © 2011 Wiley Periodicals, Inc.

Slack, Slick, and Sodium-Activated Potassium Channels

PubMed Central

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

Electrochemical potassium-ion intercalation in NaxCoO2: a novel cathode material for potassium-ion batteries.

PubMed

Sada, Krishnakanth; Senthilkumar, Baskar; Barpanda, Prabeer

2017-07-27

Reversible electrochemical potassium-ion intercalation in P2-type Na x CoO 2 was examined for the first time. Hexagonal Na 0.84 CoO 2 platelets prepared by a solution combustion synthesis technique were found to work as an efficient host for K + intercalation. They deliver a high reversible capacity of 82 mA h g -1 , good rate capability and excellent cycling performance up to 50 cycles.

Electrochemical performance of potassium-doped wüstite nanoparticles supported on graphene as an anode material for lithium ion batteries

NASA Astrophysics Data System (ADS)

Jung, Dong-Won; Jeong, Jae-Hoon; Han, Sang-Wook; Oh, Eun-Suok

2016-05-01

A graphene composite with potassium-doped FeO nanoparticles (K-FeO/graphene) is synthesized by the thermal diffusion of potassium into Fe2O3/graphene using polyol reduction. This is applied as anode material in lithium ion batteries in order to enhance the electrochemical performance of conventional iron oxides (hematite or magnetite). Rhombohedral Fe2O3 crystals are transformed into face-centered cubic FeO crystals, which show a broad d-spacing (5.2 Å) between their (111) crystal planes, by the calcination of potassium-added Fe2O3/graphene. Because of its structural characteristics, the K-FeO/graphene composite demonstrates an excellent discharge capacity of 1776 mA h g-1 at the 50th cycle at a current of 100 mA h g-1 with stable capacity retention. Even with the very high current density of 18.56 A g-1, its capacity remains at 851 mA h g-1 after 800 cycles.

In vivo Expression of a Light-activatable Potassium Channel Using Unnatural Amino Acids

PubMed Central

Kang, Ji-Yong; Kawaguchi, Daichi; Coin, Irene; Xiang, Zheng; O’Leary, Dennis D. M.; Slesinger, Paul A.; Wang, Lei

2013-01-01

SUMMARY Optical control of protein function provides excellent spatial-temporal resolution for studying proteins in situ. Although light-sensitive exogenous proteins and ligands have been employed to manipulate neuronal activity, a method for optical control of neuronal proteins using unnatural amino acids (Uaa) in vivo is lacking. Here, we describe the genetic incorporation of a photoreactive Uaa into the pore of an inwardly-rectifying potassium channel Kir2.1. The Uaa occluded the pore, rendering the channel non-conducting, and upon brief light illumination, was released to permit outward K+ current. Expression of this photo-inducible inwardly rectifying potassium (PIRK) channel in rat hippocampal neurons created a light-activatable PIRK switch for suppressing neuronal firing. We also expressed PIRK channels in embryonic mouse neocortex in vivo and demonstrated a light-activated PIRK current in cortical neurons. The principles applied here to a potassium channel could be generally expanded to other proteins expressed in the brain to enable optical regulation. PMID:24139041

Bradykinin induced a positive chronotropic effect via stimulation of T- and L-type calcium currents in heart cells.

PubMed

El-Bizri, Nesrine; Bkaily, Ghassan; Wang, Shimin; Jacques, Danielle; Regoli, Domenico; D'Orléans-Juste, Pedro; Sukarieh, Rami

2003-03-01

Using Fluo-3 calcium dye confocal microscopy and spontaneously contracting embryonic chick heart cells, bradykinin (10(-10) M) was found to induce positive chronotropic effects by increasing the frequency of the transient increase of cytosolic and nuclear free Ca2+. Pretreatment of the cells with either B1 or B2 receptor antagonists (R126 and R817, respectively) completely prevented bradykinin (BK) induced positive chronotropic effects on spontaneously contracting single heart cells. Using the whole-cell voltage clamp technique and ionic substitution to separate the different ionic current species, our results showed that BK (10(-6) M) had no effect on fast Na+ inward current and delayed outward potassium current. However, both L- and T-type Ca2+ currents were found to be increased by BK in a dose-dependent manner (10(-10)-10(-7) M). The effects of BK on T- and L-type Ca2+ currents were partially blocked by the B1 receptor antagonist [Leu8]des-Arg9-BK (R592) (10(-7) M) and completely reversed by the B2 receptor antagonist D-Arg[Hyp3,D-Phe7,Leu8]BK (R-588) (10(-7) M) or pretreatment with pertussis toxin (PTX). These results demonstrate that BK induced a positive chronotropic effect via stimulation of T- and L-type Ca2+ currents in heart cells mainly via stimulation of B2 receptor coupled to PTX-sensitive G-proteins. The increase of both types of Ca2+ current by BK in heart cells may explain the positive inotropic and chronotropic effects of this hormone.

Cesium Uptake by Rice Roots Largely Depends Upon a Single Gene, HAK1, Which Encodes a Potassium Transporter.

PubMed

Rai, Hiroki; Yokoyama, Saki; Satoh-Nagasawa, Namiko; Furukawa, Jun; Nomi, Takiko; Ito, Yasuka; Fujimura, Shigeto; Takahashi, Hidekazu; Suzuki, Ryuichiro; Yousra, ELMannai; Goto, Akitoshi; Fuji, Shinichi; Nakamura, Shin-Ichi; Shinano, Takuro; Nagasawa, Nobuhiro; Wabiko, Hiroetsu; Hattori, Hiroyuki

2017-09-01

Incidents at the Fukushima and Chernobyl nuclear power stations have resulted in widespread environmental contamination by radioactive nuclides. Among them, 137cesium has a 30 year half-life, and its persistence in soil raises serious food security issues. It is therefore important to prevent plants, especially crop plants, from absorbing radiocesium. In Arabidopsis thaliana, cesium ions are transported into root cells by several different potassium transporters such as high-affinity K+ transporter 5 (AtHAK5). Therefore, the cesium uptake pathway is thought to be highly redundant, making it difficult to develop plants with low cesium uptake. Here, we isolated rice mutants with low cesium uptake and reveal that the Oryza sativa potassium transporter OsHAK1, which is expressed on the surfaces of roots, is the main route of cesium influx into rice plants, especially in low potassium conditions. During hydroponic cultivation with low to normal potassium concentrations (0-206 µM: the normal potassium level in soil), cesium influx in OsHAK1-knockout lines was no greater than one-eighth that in the wild type. In field experiments, knockout lines of O. sativa HAK1 (OsHAK1) showed dramatically reduced cesium concentrations in grains and shoots, but their potassium uptake was not greatly affected and their grain yields were similar to that of the wild type. Our results demonstrate that, in rice roots, potassium transport systems other than OsHAK1 make little or no contribution to cesium uptake. These results show that low cesium uptake rice lines can be developed for cultivation in radiocesium-contaminated areas. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The role of calsenilin/DREAM/KChIP3 in contextual fear conditioning.

PubMed

Alexander, Jon C; McDermott, Carmel M; Tunur, Tumay; Rands, Vicky; Stelly, Claire; Karhson, Debra; Bowlby, Mark R; An, W Frank; Sweatt, J David; Schrader, Laura A

2009-03-01

Potassium channel interacting proteins (KChIPs) are members of a family of calcium binding proteins that interact with Kv4 potassium (K(+)) channel primary subunits and also act as transcription factors. The Kv4 subunit is a primary K(+) channel pore-forming subunit, which contributes to the somatic and dendritic A-type currents throughout the nervous system. These A-type currents play a key role in the regulation of neuronal excitability and dendritic processing of incoming synaptic information. KChIP3 is also known as calsenilin and as the transcription factor, downstream regulatory element antagonist modulator (DREAM), which regulates a number of genes including prodynorphin. KChIP3 and Kv4 primary channel subunits are highly expressed in hippocampus, an area of the brain important for learning and memory. Through its various functions, KChIP3 may play a role in the regulation of synaptic plasticity and learning and memory. We evaluated the role of KChIP3 in a hippocampus-dependent memory task, contextual fear conditioning. Male KChIP3 knockout (KO) mice showed significantly enhanced memory 24 hours after training as measured by percent freezing. In addition, we found that membrane association and interaction with Kv4.2 of KChIP3 protein was significantly decreased and nuclear KChIP3 expression was increased six hours after the fear conditioning training paradigm with no significant change in KChIP3 mRNA. In addition, prodynorphin mRNA expression was significantly decreased six hours after fear conditioning training in wild-type (WT) but not in KO animals. These data suggest a role for regulation of gene expression by KChIP3/DREAM/calsenilin in consolidation of contextual fear conditioning memories.

The delayed rectifier, IKI, is the major conductance in type I vestibular hair cells across vestibular end organs

NASA Technical Reports Server (NTRS)

Ricci, A. J.; Rennie, K. J.; Correia, M. J.

1996-01-01

Hair cells were dissociated from the semicircular canal, utricle, lagena and saccule of white king pigeons. Type I hair cells were identified morphologically based on the ratios of neck width to cuticular plate width (NPR < 0.72) as well as neck width to cell body width (NBR < 0.64). The perforated patch variant of the whole-cell recording technique was used to measure electrical properties from type I hair cells. In voltage-clamp, the membrane properties of all identified type I cells were dominated by a predominantly outward potassium current, previously characterized in semicircular canal as IKI. Zero-current potential, activation, deactivation, slope conductance, pharmacologic and steady-state properties of the complex currents were not statistically different between type I hair cells of different vestibular end organs. The voltage dependence causes a significant proportion of this conductance to be active about the cell's zero-current potential. The first report of the whole-cell activation kinetics of the conductance is presented, showing a voltage dependence that could be best fit by an equation for a single exponential. Results presented here are the first data from pigeon dissociated type I hair cells from utricle, saccule and lagena suggesting that the basolateral conductances of a morphologically identified population of type I hair cells are conserved between functionally different vestibular end organs; the major conductance being a delayed rectifier characterized previously in semicircular canal hair cells as IKI.

Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion.

PubMed

Gaddam, Krishna K; Nishizaka, Mari K; Pratt-Ubunama, Monique N; Pimenta, Eduardo; Aban, Inmaculada; Oparil, Suzanne; Calhoun, David A

2008-06-09

Resistant hypertension is a common clinical problem and greatly increases the risk of target organ damage. We evaluated the characteristics of 279 consecutive patients with resistant hypertension (uncontrolled despite the use of 3 antihypertensive agents) and 53 control subjects (with normotension or hypertension controlled by using

Expression and distribution of Kv4 potassium channel subunits and potassium channel interacting proteins in subpopulations of interneurons in the basolateral amygdala.

PubMed

Dabrowska, J; Rainnie, D G

2010-12-15

The Kv4 potassium channel α subunits, Kv4.1, Kv4.2, and Kv4.3, determine some of the fundamental physiological properties of neurons in the CNS. Kv4 subunits are associated with auxiliary β-subunits, such as the potassium channel interacting proteins (KChIP1 - 4), which are thought to regulate the trafficking and gating of native Kv4 potassium channels. Intriguingly, KChIP1 is thought to show cell type-selective expression in GABA-ergic inhibitory interneurons, while other β-subunits (KChIP2-4) are associated with principal glutamatergic neurons. However, nothing is known about the expression of Kv4 family α- and β-subunits in specific interneurons populations in the BLA. Here, we have used immunofluorescence, co-immunoprecipitation, and Western Blotting to determine the relative expression of KChIP1 in the different interneuron subtypes within the BLA, and its co-localization with one or more of the Kv4 α subunits. We show that all three α-subunits of Kv4 potassium channel are found in rat BLA neurons, and that the immunoreactivity of KChIP1 closely resembles that of Kv4.3. Indeed, Kv4.3 showed almost complete co-localization with KChIP1 in the soma and dendrites of a distinct subpopulation of BLA neurons. Dual-immunofluorescence studies revealed this to be in BLA interneurons immunoreactive for parvalbumin, cholecystokin-8, and somatostatin. Finally, co-immunoprecipitation studies showed that KChIP1 was associated with all three Kv4 α subunits. Together our results suggest that KChIP1 is selectively expressed in BLA interneurons where it may function to regulate the activity of A-type potassium channels. Hence, KChIP1 might be considered as a cell type-specific regulator of GABAergic inhibitory circuits in the BLA. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

A low cost, high energy density, and long cycle life potassium-sulfur battery for grid-scale energy storage.

PubMed

Lu, Xiaochuan; Bowden, Mark E; Sprenkle, Vincent L; Liu, Jun

2015-10-21

A potassium-sulfur battery using K(+) -conducting beta-alumina as the electrolyte to separate a molten potassium metal anode and a sulfur cathode is presented. The results indicate that the battery can operate at as low as 150 °C with excellent performance. This study demonstrates a new type of high-performance metal-sulfur battery that is ideal for grid-scale energy-storage applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular physiology and modulation of somatodendritic A-type potassium channels.

PubMed

Jerng, Henry H; Pfaffinger, Paul J; Covarrubias, Manuel

2004-12-01

The somatodendritic subthreshold A-type K+ current (ISA) in nerve cells is a critical component of the ensemble of voltage-gated ionic currents that determine somatodendritic signal integration. The underlying K+ channel belongs to the Shal subfamily of voltage-gated K+ channels. Most Shal channels across the animal kingdom share a high degree of structural conservation, operate in the subthreshold range of membrane potentials, and exhibit relatively fast inactivation and recovery from inactivation. Mammalian Shal K+ channels (Kv4) undergo preferential closed-state inactivation with features that are generally inconsistent with the classical mechanisms of inactivation typical of Shaker K+ channels. Here, we review (1) the physiological and genetic properties of ISA, 2 the molecular mechanisms of Kv4 inactivation and its remodeling by a family of soluble calcium-binding proteins (KChIPs) and a membrane-bound dipeptidase-like protein (DPPX), and (3) the modulation of Kv4 channels by protein phosphorylation.

The ionic bases of the action potential in isolated mouse cardiac Purkinje cell.

PubMed

Vaidyanathan, Ravi; O'Connell, Ryan P; Deo, Makarand; Milstein, Michelle L; Furspan, Philip; Herron, Todd J; Pandit, Sandeep V; Musa, Hassan; Berenfeld, Omer; Jalife, José; Anumonwo, Justus M B

2013-01-01

Collecting electrophysiological and molecular data from the murine conduction system presents technical challenges. Thus, only little advantage has been taken of numerous genetically engineered murine models to study excitation through the cardiac conduction system of the mouse. To develop an approach for isolating murine cardiac Purkinje cells (PCs), to characterize major ionic currents and to use the data to simulate action potentials (APs) recorded from PCs. Light microscopy was used to isolate and identify PCs from apical and septal cells. Current and voltage clamp techniques were used to record APs and whole cell currents. We then simulated a PC AP on the basis of our experimental data. APs recorded from PCs were significantly longer than those recorded from ventricular cells. The prominent plateau phase of the PC AP was very negative (≈-40 mV). Spontaneous activity was observed only in PCs. The inward rectifier current demonstrated no significant differences compared to ventricular myocytes (VMs). However, sodium current density was larger, and the voltage-gated potassium current density was significantly less in PCs compared with myocytes. T-type Ca(2+) currents (I(Ca,T)) were present in PCs but not VMs. Computer simulations suggest that I(Ca,T) and cytosolic calcium diffusion significantly modulate AP profile recorded in PCs, as compared to VMs. Our study provides the first comprehensive ionic profile of murine PCs. The data show unique features of PC ionic mechanisms that govern its excitation process. Experimental data and numerical modeling results suggest that a smaller voltage-gated potassium current and the presence of I(Ca,T) are important determinants of the longer and relatively negative plateau phase of the APs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Genistein inhibition of OGD-induced brain neuron death correlates with its modulation of apoptosis, voltage-gated potassium and sodium currents and glutamate signal pathway.

PubMed

Ma, Xue-Ling; Zhang, Feng; Wang, Yu-Xiang; He, Cong-Cong; Tian, Kun; Wang, Hong-Gang; An, Di; Heng, Bin; Liu, Yan-Qiang

2016-07-25

In the present study, we established an in vitro model of hypoxic-ischemia via exposing primary neurons of newborn rats to oxygen-glucose deprivation (OGD) and observing the effects of genistein, a soybean isoflavone, on hypoxic-ischemic neuron viability, apoptosis, voltage-activated potassium (Kv) and sodium (Nav) currents, and glutamate receptor subunits. The results indicated that OGD exposure reduced the viability and increased the apoptosis of brain neurons. Meanwhile, OGD exposure caused changes in the current-voltage curves and current amplitude values of voltage-activated potassium and sodium currents; OGD exposure also decreased GluR2 expression and increased NR2 expression. However, genistein at least partially reversed the effects caused by OGD. The results suggest that hypoxic-ischemia-caused neuronal apoptosis/death is related to an increase in K(+) efflux, a decrease in Na(+) influx, a down-regulation of GluR2, and an up-regulation of NR2. Genistein may exert some neuroprotective effects via the modulation of Kv and Nav currents and the glutamate signal pathway, mediated by GluR2 and NR2. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus.

PubMed

Xiang, Yu-luan; He, Li; Xiao, Jun; Xia, Shuang; Deng, Song-bai; Xiu, Yun; She, Qiang

2012-03-01

Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM + TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg-1·day-1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

A High-Energy-Density Potassium Battery with a Polymer-Gel Electrolyte and a Polyaniline Cathode.

PubMed

Gao, Hongcai; Xue, Leigang; Xin, Sen; Goodenough, John B

2018-05-04

A safe, rechargeable potassium battery of high energy density and excellent cycling stability has been developed. The anion component of the electrolyte salt is inserted into a polyaniline cathode upon charging and extracted from it during discharging while the K + ion of the KPF 6 salt is plated/stripped on the potassium-metal anode. The use of a p-type polymer cathode increases the cell voltage. By replacing the organic-liquid electrolyte in a glass-fiber separator with a polymer-gel electrolyte of cross-linked poly(methyl methacrylate), a dendrite-free potassium anode can be plated/stripped, and the electrode/electrolyte interface is stabilized. The potassium anode wets the polymer, and the cross-linked architecture provides small pores of adjustable sizes to stabilize a solid-electrolyte interphase formed at the anode/electrolyte interface. This alternative electrolyte/cathode strategy offers a promising new approach to low-cost potassium batteries for the stationary storage of electric power. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ion Fluxes in Giant Excised Cardiac Membrane Patches Detected and Quantified with Ion-selective Microelectrodes

PubMed Central

Kang, Tong Mook; Markin, Vladislav S.; Hilgemann, Donald W.

2003-01-01

We have used ion-selective electrodes (ISEs) to quantify ion fluxes across giant membrane patches by measuring and simulating ion gradients on both membrane sides. Experimental conditions are selected with low concentrations of the ions detected on the membrane side being monitored. For detection from the cytoplasmic (bath) side, the patch pipette is oscillated laterally in front of an ISE. For detection on the extracellular (pipette) side, ISEs are fabricated from flexible quartz capillary tubing (tip diameters, 2–3 microns), and an ISE is positioned carefully within the patch pipette with the tip at a controlled distance from the mouth of the patch pipette. Transport activity is then manipulated by solution changes on the cytoplasmic side. Ion fluxes can be quantified by simulating the ion gradients with appropriate diffusion models. For extracellular (intrapatch pipette) recordings, ion diffusion coefficients can be determined from the time courses of concentration changes. The sensitivity and utility of the methods are demonstrated with cardiac membrane patches by measuring (a) potassium fluxes via ion channels, valinomycin, and Na/K pumps; (b) calcium fluxes mediated by Na/Ca exchangers; (c) sodium fluxes mediated by gramicidin and Na/K pumps; and (d) proton fluxes mediated by an unknown electrogenic mechanism. The potassium flux-to-current ratio for the Na/K pump is approximately twice that determined for potassium channels and valinomycin, as expected for a 3Na/2K pump stoichiometery (i.e., 2K/charge moved). For valinomycin-mediated potassium currents and gramicidin-mediated sodium currents, the ion fluxes calculated from diffusion models are typically 10–15% smaller than expected from the membrane currents. As presently implemented, the ISE methods allow reliable detection of calcium and proton fluxes equivalent to monovalent cation currents <1 pA in magnitude, and they allow detection of sodium and potassium fluxes equivalent to <5 pA currents. The capability to monitor ion fluxes, independent of membrane currents, should facilitate studies of both electrogenic and electroneutral ion–coupled transporters in giant patches. PMID:12668735

Serum potassium and the racial disparity in diabetes risk: the Atherosclerosis Risk in Communities (ARIC) Study1234

PubMed Central

Chatterjee, Ranee; Yeh, Hsin-Chieh; Shafi, Tariq; Anderson, Cheryl; Pankow, James S; Miller, Edgar R; Levine, David; Selvin, Elizabeth; Brancati, Frederick L

2011-01-01

Background: Low serum potassium appears to be independently associated with incident type 2 diabetes, and low dietary potassium is more common in African Americans than in whites. Objective: We hypothesized that low serum potassium contributes to the excess risk of diabetes in African Americans. Design: We analyzed data collected from 1987 to 1996 from the Atherosclerosis Risk in Communities (ARIC) Study. At baseline, we identified 2716 African American and 9493 white participants without diabetes. We used multivariate Cox models to estimate the relative hazards (RHs) of incident diabetes related to baseline serum potassium during 9 y of follow-up. Results: Mean serum potassium concentrations were lower in African Americans than in whites at baseline (4.2 compared with 4.5 mEq/L; P < 0.01), and African Americans had a greater incidence of diabetes than did whites (26 compared with 13 cases/1000 person-years). The adjusted RHs (95% CI) of incident diabetes for those with serum potassium concentrations of <4.0, 4.0–4.4, and 4.5–4.9 mEq/L, compared with those with serum potassium concentrations of 5.0–5.5 mEq/L (referent), were 2.28 (1.21, 4.28), 1.97 (1.06, 3.65), and 1.85 (0.99, 3.47) for African Americans and 1.53 (1.14, 2.05), 1.49 (1.19, 1.87), and 1.27 (1.02, 1.58) for whites, respectively. Racial differences in serum potassium appeared to explain 18% of the excess risk of diabetes in African Americans, which is comparable with the percentage of risk explained by racial differences in body mass index (22%). Conclusions: Low serum potassium concentrations in African Americans may contribute to their excess risk of type 2 diabetes relative to whites. Whether interventions to increase serum potassium concentrations in African Americans might reduce their excess risk deserves further study. The ARIC Study is registered at clinicaltrials.gov as NCT00005131. PMID:21367942

Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Baode; Li, Chenxing

Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5–50.0 mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I{submore » Kv1.5}) were markedly inhibited by 12.5–50.0 mM ethanol in a concentration-dependent manner. Ethanol with 50.0 mM could inhibit rapid delayed rectifier potassium currents (I{sub hERG}). Ethanol under 6.25–50.0 mM did not affect on inward rectifier potassium currents (I{sub Kir2.1}). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I{sub Kv1.5} and I{sub hERG}, which contributed to preventing the development and duration of AF. - Highlights: • Moderate ethanol prevented the development of AF in animal models. • Moderate ethanol prolonged APD in guinea pig atrial myocytes. • Moderate ethanol inhibited Kv1.5 currents.« less

A new method of auxiliary purification for motor vehicle exhaust.

PubMed

Li, Dingqi

2018-07-01

As a result of the limitations of current purification technologies, purification efficiency is relatively low, particularly during startup or in the case of other abnormal automobile exhaust. Therefore, a new method of auxiliary purification is proposed in this paper. The acidic solution of potassium permanganate can oxidize carbon monoxide, nitrogen oxides and sulfur dioxide at relatively high temperatures and the alkaline solution of potassium permanganate can selectively absorb nitrogen oxide and sulfur dioxide. Therefore, we carried out the experiment using a solution of potassium permanganate and sulfuric acid as well as a solution of sodium carbonate and potassium permanganate, which served as the reagents for the auxiliary purification. The results of the test showed that after auxiliary purification by the acidic solution of potassium permanganate and the alkaline solution of potassium permanganate, the concentrations of carbon monoxide, hydrocarbons, nitrogen oxides and solid particles in the emissions were considerably lower than the concentrations prior to purification. It is possible to reduce the motor vehicle exhaust by the auxiliary purification of the solutions.

Kcne2 deletion impairs insulin secretion and causes type 2 diabetes mellitus.

PubMed

Lee, Soo Min; Baik, Jasmine; Nguyen, Dara; Nguyen, Victoria; Liu, Shiwei; Hu, Zhaoyang; Abbott, Geoffrey W

2017-06-01

Type 2 diabetes mellitus (T2DM) represents a rapidly increasing threat to global public health. T2DM arises largely from obesity, poor diet, and lack of exercise, but it also involves genetic predisposition. Here we report that the KCNE2 potassium channel transmembrane regulatory subunit is expressed in human and mouse pancreatic β cells. Kcne2 deletion in mice impaired glucose tolerance as early as 5 wk of age in pups fed a Western diet, ultimately causing diabetes. In adult mice fed normal chow, skeletal muscle expression of insulin receptor β and insulin receptor substrate 1 were down-regulated 2-fold by Kcne2 deletion, characteristic of T2DM. Kcne2 deletion also caused extensive pancreatic transcriptome changes consistent with facets of T2DM, including endoplasmic reticulum stress, inflammation, and hyperproliferation. Kcne2 deletion impaired β-cell insulin secretion in vitro up to 8-fold and diminished β-cell peak outward K + current at positive membrane potentials, but also left-shifted its voltage dependence and slowed inactivation. Interestingly, we also observed an aging-dependent reduction in β-cell outward currents in both Kcne2 +/+ and Kcne2 - / - mice. Our results demonstrate that KCNE2 is required for normal β-cell electrical activity and insulin secretion, and that Kcne2 deletion causes T2DM. KCNE2 may regulate multiple K + channels in β cells, including the T2DM-linked KCNQ1 potassium channel α subunit.-Lee, S. M., Baik, J., Nguyen, D., Nguyen, V., Liu, S., Hu, Z., Abbott, G. W. Kcne2 deletion impairs insulin secretion and causes type 2 diabetes mellitus. © FASEB.

Inward rectifier potassium current IKir promotes intrinsic pacemaker activity of thalamocortical neurons.

PubMed

Amarillo, Yimy; Tissone, Angela I; Mato, Germán; Nadal, Marcela S

2018-06-01

Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (<4 Hz), which are the physiological oscillations during non-rapid eye movement sleep or pathological oscillations during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that upregulation of the small and neglected inward rectifier potassium current I Kir induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mouse TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explains how the unique properties of I Kir enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage- and time-dependent interaction of I Kir and hyperpolarization-activated cationic current I h that endows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. Bifurcation analysis of conductance-based models of increasing complexity demonstrates that I Kir induces bistability of the membrane potential at the same time that it induces sustained oscillations in combination with I h and increases the robustness of low threshold-activated calcium current I T -mediated oscillations. NEW & NOTEWORTHY The strong inwardly rectifying potassium current I Kir of thalamocortical neurons displays a region of negative slope conductance in the current-voltage relationship that generates potassium currents activated by hyperpolarization. Bifurcation analysis shows that I Kir induces bistability of the membrane potential; generates sustained subthreshold oscillations by interacting with the hyperpolarization-activated cationic current I h ; and increases the robustness of oscillations mediated by the low threshold-activated calcium current I T . Upregulation of I Kir in thalamocortical neurons induces repetitive burst firing at slow and delta frequency bands (<4 Hz).

Effects of cell volume changes on membrane ionic permeabilities and sodium transport in frog skin (Rana ridibunda).

PubMed

Costa, P M; Fernandes, P L; Ferreira, H G; Ferreira, K T; Giraldez, F

1987-12-01

1. Membrane potential and conductances and short-circuit current were continuously measured with microelectrodes and conventional electrophysiological techniques in a stripped preparation of frog skin epithelium. The effects of the removal of chloride or sodium ions and the concentration or dilution of the serosal (inner) bathing solution were studied. 2. Chloride- or sodium-free solutions produced a cell depolarization of about 30 mV in parallel with a fall in the short-circuit current. Mucosal and serosal membrane conductances both decreased and the sodium permeability of the mucosal barrier was calculated to fall to about one-half its value in standard Ringer solution. The observed decrease in the short-circuit current is probably related to the combined effect of the decrease in sodium permeability and the decrease in the driving force across the mucosal membrane. 3. The removal of chloride or sodium ions reduced the depolarization caused by serosal perfusion with high-potassium solutions (50 mM-KCl). The ratio of the change in cell membrane potential under short-circuit conditions to the change in the potassium equilibrium potential (delta Ec(s.c.)/delta EK), was 0.59 in standard Ringer solution and 0.26 and 0.24 after the removal of chloride or sodium respectively. The depolarizing effect of barium-containing solutions (2 mM-BaCl2) was also markedly reduced in chloride- or sodium-free solutions, suggesting a decrease of the potassium selectivity of the serosal membrane in these conditions. 4. Increasing the osmolality of the serosal bathing solution produced similar effects, i.e. cell depolarization, fall in the short-circuit current and membrane conductances and reduction of the depolarizing effect of high-potassium and barium solutions. On the contrary, dilution of the serosal bath produced the opposite effects, consistent with an increase in the serosal permeability to potassium. 5. The effects of chloride- or sodium-free solutions were reversed by the dilution of the serosal bath. Cells repolarized when exposed to low-osmolality solutions after being in the absence of serosal chloride or sodium. The repolarization ran in parallel with the restoration of the short-circuit current and the potassium selectivity of the serosal membrane. 6. The results show that the effects produced by the removal of sodium or chloride ions from the serosal bathing solution are most probably mediated by a reduction in cell volume. Cell volume changes would lead to changes in the serosal membrane selectivity to potassium and thus to changes in cell membrane potential and sodium transport.(ABSTRACT TRUNCATED AT 400 WORDS)

Sustainable Potassium-Ion Battery Anodes Derived from Waste-Tire Rubber

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yunchao; Adams, Ryan A.; Arora, Anjela

The recycling of waste-tire rubber is of critical importance since the discarded tires pose serious environmental and health hazards to our society. Here, we report a new application for hard-carbon materials derived from waste-tires as anodes in potassium-ion batteries. The sustainable tire-derived carbons show good reversible potassium insertion at relatively high rates. Long-term stability tests exhibit capacities of 155 and 141 mAh g –1 for carbon pyrolyzed at 1100°C and 1600°C, respectively, after 200 cycles at current rate of C/2. As a result, this study provides an alternative solution for inexpensive and environmental benign potassium-ion battery anode materials.

Sustainable Potassium-Ion Battery Anodes Derived from Waste-Tire Rubber

DOE PAGES

Li, Yunchao; Adams, Ryan A.; Arora, Anjela; ...

2017-04-13

The recycling of waste-tire rubber is of critical importance since the discarded tires pose serious environmental and health hazards to our society. Here, we report a new application for hard-carbon materials derived from waste-tires as anodes in potassium-ion batteries. The sustainable tire-derived carbons show good reversible potassium insertion at relatively high rates. Long-term stability tests exhibit capacities of 155 and 141 mAh g –1 for carbon pyrolyzed at 1100°C and 1600°C, respectively, after 200 cycles at current rate of C/2. As a result, this study provides an alternative solution for inexpensive and environmental benign potassium-ion battery anode materials.

A Disease Mutation Causing Episodic Ataxia Type I in the S1 Links Directly to the Voltage Sensor and the Selectivity Filter in Kv Channels.

PubMed

Petitjean, Dimitri; Kalstrup, Tanja; Zhao, Juan; Blunck, Rikard

2015-09-02

The mutation F184C in Kv1.1 leads to development of episodic ataxia type I (EA1). Although the mutation has been said to alter activation kinetics and to lower expression, we show here that the underlying molecular mechanisms may be more complex. Although F184 is positioned in the "peripheral" S1 helix, it occupies a central position in the 3D fold. We show in cut-open oocyte voltage-clamp recordings of gating and ionic currents of the Shaker Kv channel expressed in Xenopus oocytes that F184 not only interacts directly with the gating charges of the S4, but also creates a functional link to the selectivity filter of the neighboring subunit. This link leads to impaired fast and slow inactivation. The effect on fast inactivation is of an allosteric nature considering that fast inactivation is caused by a linked cytosolic ball peptide. The extensive effects of F184C provide a new mechanism underlying EA. Episodic ataxia (EA) is an inherited disease that leads to occasional loss of motor control in combination with variable other symptoms such as vertigo or migraine. EA type I (EA1), studied here, is caused by mutations in a voltage-gated potassium channel that contributes to the generation of electrical signals in the brain. The mechanism by which mutations in voltage-gated potassium channels lead to EA is still unknown and there is no consistent pharmacological treatment. By studying in detail one disease-causing mutation in Kv1.1, we describe a novel molecular mechanism distinct from mechanisms described previously. This mechanism contributes to the understanding of potassium channel function in general and might lead to a better understanding of how EA develops. Copyright © 2015 the authors 0270-6474/15/3512198-09$15.00/0.

Dietary Impact of Adding Potassium Chloride to Foods as a Sodium Reduction Technique.

PubMed

van Buren, Leo; Dötsch-Klerk, Mariska; Seewi, Gila; Newson, Rachel S

2016-04-21

Potassium chloride is a leading reformulation technology for reducing sodium in food products. As, globally, sodium intake exceeds guidelines, this technology is beneficial; however, its potential impact on potassium intake is unknown. Therefore, a modeling study was conducted using Dutch National Food Survey data to examine the dietary impact of reformulation (n = 2106). Product-specific sodium criteria, to enable a maximum daily sodium chloride intake of 5 grams/day, were applied to all foods consumed in the survey. The impact of replacing 20%, 50% and 100% of sodium chloride from each product with potassium chloride was modeled. At baseline median, potassium intake was 3334 mg/day. An increase in the median intake of potassium of 453 mg/day was seen when a 20% replacement was applied, 674 mg/day with a 50% replacement scenario and 733 mg/day with a 100% replacement scenario. Reformulation had the largest impact on: bread, processed fruit and vegetables, snacks and processed meat. Replacement of sodium chloride by potassium chloride, particularly in key contributing product groups, would result in better compliance to potassium intake guidelines (3510 mg/day). Moreover, it could be considered safe for the general adult population, as intake remains compliant with EFSA guidelines. Based on current modeling potassium chloride presents as a valuable, safe replacer for sodium chloride in food products.

Loss of Functional A-Type Potassium Channels in the Dendrites of CA1 Pyramidal Neurons from a Mouse Model of Fragile X Syndrome

PubMed Central

Routh, Brandy N.; Johnston, Daniel

2013-01-01

Despite the critical importance of voltage-gated ion channels in neurons, very little is known about their functional properties in Fragile X syndrome: the most common form of inherited cognitive impairment. Using three complementary approaches, we investigated the physiological role of A-type K+ currents (IKA) in hippocampal CA1 pyramidal neurons from fmr1-/y mice. Direct measurement of IKA using cell-attached patch-clamp recordings revealed that there was significantly less IKA in the dendrites of CA1 neurons from fmr1-/y mice. Interestingly, the midpoint of activation for A-type K+ channels was hyperpolarized for fmr1-/y neurons compared with wild-type, which might partially compensate for the lower current density. Because of the rapid time course for recovery from steady-state inactivation, the dendritic A-type K+ current in CA1 neurons from both wild-type and fmr1-/y mice is likely mediated by KV4 containing channels. The net effect of the differences in IKA was that back-propagating action potentials had larger amplitudes producing greater calcium influx in the distal dendrites of fmr1-/y neurons. Furthermore, CA1 pyramidal neurons from fmr1-/y mice had a lower threshold for LTP induction. These data suggest that loss of IKA in hippocampal neurons may contribute to dendritic pathophysiology in Fragile X syndrome. PMID:24336711

Developing strategies for predicting hyperkalemia in potassium-increasing drug-drug interactions.

PubMed

Eschmann, Emmanuel; Beeler, Patrick Emanuel; Schneemann, Markus; Blaser, Jürg

2017-01-01

To compare different strategies predicting hyperkalemia (serum potassium level ≥5.5 mEq/l) in hospitalized patients for whom medications triggering potassium-increasing drug-drug interactions (DDIs) were ordered. We investigated 5 strategies that combined prediction triggered at onset of DDI versus continuous monitoring and taking into account an increasing number of patient parameters. The considered patient parameters were identified using generalized additive models, and the thresholds of the prediction strategies were calculated by applying Youden's J statistic to receiver operation characteristic curves. Half of the data served as the calibration set, half as the validation set. We identified 132 incidences of hyperkalemia induced by 8413 potentially severe potassium-increasing DDIs among 76 467 patients. The positive predictive value (PPV) of those strategies predicting hyperkalemia at the onset of DDI ranged from 1.79% (undifferentiated anticipation of hyperkalemia due to the DDI) to 3.02% (additionally considering the baseline serum potassium) and 3.10% (including further patient parameters). Continuous monitoring significantly increased the PPV to 8.25% (considering the current serum potassium) and 9.34% (additional patient parameters). Continuous monitoring of the risk for hyperkalemia based on current potassium level shows a better predictive power than predictions triggered at the onset of DDI. This contrasts with efforts to improve DDI alerts by taking into account more patient parameters at the time of ordering. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dietary Protein and Potassium, Diet-Dependent Net Acid Load, and Risk of Incident Kidney Stones.

PubMed

Ferraro, Pietro Manuel; Mandel, Ernest I; Curhan, Gary C; Gambaro, Giovanni; Taylor, Eric N

2016-10-07

Protein and potassium intake and the resulting diet-dependent net acid load may affect kidney stone formation. It is not known whether protein type or net acid load is associated with risk of kidney stones. We prospectively examined intakes of protein (dairy, nondairy animal, and vegetable), potassium, and animal protein-to-potassium ratio (an estimate of net acid load) and risk of incident kidney stones in the Health Professionals Follow-Up Study ( n =42,919), the Nurses' Health Study I ( n =60,128), and the Nurses' Health Study II ( n =90,629). Multivariable models were adjusted for age, body mass index, diet, and other factors. We also analyzed cross-sectional associations with 24-hour urine ( n =6129). During 3,108,264 person-years of follow-up, there were 6308 incident kidney stones. Dairy protein was associated with lower risk in the Nurses' Health Study II (hazard ratio for highest versus lowest quintile, 0.84; 95% confidence interval, 0.73 to 0.96; P value for trend <0.01). The hazard ratios for nondairy animal protein were 1.15 (95% confidence interval, 0.97 to 1.36; P value for trend =0.04) in the Health Professionals Follow-Up Study and 1.20 (95% confidence interval, 0.99 to 1.46; P value for trend =0.06) in the Nurses' Health Study I. Potassium intake was associated with lower risk in all three cohorts (hazard ratios from 0.44 [95% confidence interval, 0.36 to 0.53] to 0.67 [95% confidence interval, 0.57 to 0.78]; P values for trend <0.001). Animal protein-to-potassium ratio was associated with higher risk ( P value for trend =0.004), even after adjustment for animal protein and potassium. Higher dietary potassium was associated with higher urine citrate, pH, and volume ( P values for trend <0.002). Kidney stone risk may vary by protein type. Diets high in potassium or with a relative abundance of potassium compared with animal protein could represent a means of stone prevention. Copyright © 2016 by the American Society of Nephrology.

Dietary Protein and Potassium, Diet–Dependent Net Acid Load, and Risk of Incident Kidney Stones

PubMed Central

Mandel, Ernest I.; Curhan, Gary C.; Gambaro, Giovanni; Taylor, Eric N.

2016-01-01

Background and objectives Protein and potassium intake and the resulting diet–dependent net acid load may affect kidney stone formation. It is not known whether protein type or net acid load is associated with risk of kidney stones. Design, setting, participants, & measurements We prospectively examined intakes of protein (dairy, nondairy animal, and vegetable), potassium, and animal protein-to-potassium ratio (an estimate of net acid load) and risk of incident kidney stones in the Health Professionals Follow-Up Study (n=42,919), the Nurses’ Health Study I (n=60,128), and the Nurses’ Health Study II (n=90,629). Multivariable models were adjusted for age, body mass index, diet, and other factors. We also analyzed cross-sectional associations with 24-hour urine (n=6129). Results During 3,108,264 person-years of follow-up, there were 6308 incident kidney stones. Dairy protein was associated with lower risk in the Nurses’ Health Study II (hazard ratio for highest versus lowest quintile, 0.84; 95% confidence interval, 0.73 to 0.96; P value for trend <0.01). The hazard ratios for nondairy animal protein were 1.15 (95% confidence interval, 0.97 to 1.36; P value for trend =0.04) in the Health Professionals Follow-Up Study and 1.20 (95% confidence interval, 0.99 to 1.46; P value for trend =0.06) in the Nurses’ Health Study I. Potassium intake was associated with lower risk in all three cohorts (hazard ratios from 0.44 [95% confidence interval, 0.36 to 0.53] to 0.67 [95% confidence interval, 0.57 to 0.78]; P values for trend <0.001). Animal protein-to-potassium ratio was associated with higher risk (P value for trend =0.004), even after adjustment for animal protein and potassium. Higher dietary potassium was associated with higher urine citrate, pH, and volume (P values for trend <0.002). Conclusions Kidney stone risk may vary by protein type. Diets high in potassium or with a relative abundance of potassium compared with animal protein could represent a means of stone prevention. PMID:27445166

Stimulation of Slack K(+) Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex.

PubMed

Fleming, Matthew R; Brown, Maile R; Kronengold, Jack; Zhang, Yalan; Jenkins, David P; Barcia, Gulia; Nabbout, Rima; Bausch, Anne E; Ruth, Peter; Lukowski, Robert; Navaratnam, Dhasakumar S; Kaczmarek, Leonard K

2016-08-30

Human mutations in the cytoplasmic C-terminal domain of Slack sodium-activated potassium (KNa) channels result in childhood epilepsy with severe intellectual disability. Slack currents can be increased by pharmacological activators or by phosphorylation of a Slack C-terminal residue by protein kinase C. Using an optical biosensor assay, we find that Slack channel stimulation in neurons or transfected cells produces loss of mass near the plasma membrane. Slack mutants associated with intellectual disability fail to trigger any change in mass. The loss of mass results from the dissociation of the protein phosphatase 1 (PP1) targeting protein, Phactr-1, from the channel. Phactr1 dissociation is specific to wild-type Slack channels and is not observed when related potassium channels are stimulated. Our findings suggest that Slack channels are coupled to cytoplasmic signaling pathways and that dysregulation of this coupling may trigger the aberrant intellectual development associated with specific childhood epilepsies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Stimulation of Slack K+ channels alters mass at the plasma membrane by triggering dissociation of a phosphatase-regulatory complex

PubMed Central

Fleming, Matthew R.; Brown, Maile R.; Kronengold, Jack; Zhang, Yalan; Jenkins, David P.; Barcia, Gulia; Nabbout, Rima; Bausch, Anne E.; Ruth, Peter; Lukowski, Robert; Navaratnam, Dhasakumar S.; Kaczmarek, Leonard K.

2016-01-01

Summary Human mutations in the cytoplasmic C-terminal domain of Slack sodium-activated potassium (KNa) channels result in childhood epilepsy with severe intellectual disability. Slack currents can be increased by pharmacological activators or by phosphorylation of a Slack C-terminal residue by protein kinase C. Using an optical biosensor assay, we find that Slack channel stimulation in neurons or transfected cells produces loss of mass near the plasma membrane. Slack mutants associated with intellectual disability fail to trigger any change in mass. The loss of mass results from the dissociation of the protein phosphatase 1 (PP1) targeting protein, Phactr-1, from the channel. Phactr1 dissociation is specific to wild-type Slack channels and is not observed when related potassium channels are stimulated. Our findings suggest that Slack channels are coupled to cytoplasmic signaling pathways, and that dysregulation of this coupling may trigger the aberrant intellectual development associated with specific childhood epilepsies. PMID:27545877

Effect of tyrphostin AG879 on Kv4.2 and Kv4.3 potassium channels

PubMed Central

Yu, Haibo; Zou, Beiyan; Wang, Xiaoliang; Li, Min

2015-01-01

Background and Purpose A-type potassium channels (IA) are important proteins for modulating neuronal membrane excitability. The expression and activity of Kv4.2 channels are critical for neurological functions and pharmacological inhibitors of Kv4.2 channels may have therapeutic potential for Fragile X syndrome. While screening various compounds, we identified tyrphostin AG879, a tyrosine kinase inhibitor, as a Kv4.2 inhibitor from. In the present study we characterized the effect of AG879 on cloned Kv4.2/Kv channel-interacting protein 2 (KChIP2) channels. Experimental Approach To screen the library of pharmacologically active compounds, the thallium flux assay was performed on HEK-293 cells transiently-transfected with Kv4.2 cDNA using the Maxcyte transfection system. The effects of AG879 were further examined on CHO-K1 cells expressing Kv4.2/KChIP2 channels using a whole-cell patch-clamp technique. Key Results Tyrphostin AG879 selectively and dose-dependently inhibited Kv4.2 and Kv4.3 channels. In Kv4.2/KChIP2 channels, AG879 induced prominent acceleration of the inactivation rate, use-dependent block and slowed the recovery from inactivation. AG879 induced a hyperpolarizing shift in the voltage-dependence of the steady-state inactivation of Kv4.2 channels without apparent effect on the V1/2 of the voltage-dependent activation. The blocking effect of AG879 was enhanced as channel inactivation increased. Furthermore, AG879 significantly inhibited the A-type potassium currents in the cultured hippocampus neurons. Conclusion and Implications AG879 was identified as a selective and potent inhibitor the Kv4.2 channel. AG879 inhibited Kv4.2 channels by preferentially interacting with the open state and further accelerating their inactivation. PMID:25752739

Effect of tyrphostin AG879 on Kv 4.2 and Kv 4.3 potassium channels.

PubMed

Yu, Haibo; Zou, Beiyan; Wang, Xiaoliang; Li, Min

2015-07-01

A-type potassium channels (IA) are important proteins for modulating neuronal membrane excitability. The expression and activity of Kv 4.2 channels are critical for neurological functions and pharmacological inhibitors of Kv 4.2 channels may have therapeutic potential for Fragile X syndrome. While screening various compounds, we identified tyrphostin AG879, a tyrosine kinase inhibitor, as a Kv 4.2 inhibitor from. In the present study we characterized the effect of AG879 on cloned Kv 4.2/Kv channel-interacting protein 2 (KChIP2) channels. To screen the library of pharmacologically active compounds, the thallium flux assay was performed on HEK-293 cells transiently-transfected with Kv 4.2 cDNA using the Maxcyte transfection system. The effects of AG879 were further examined on CHO-K1 cells expressing Kv 4.2/KChIP2 channels using a whole-cell patch-clamp technique. Tyrphostin AG879 selectively and dose-dependently inhibited Kv 4.2 and Kv 4.3 channels. In Kv 4.2/KChIP2 channels, AG879 induced prominent acceleration of the inactivation rate, use-dependent block and slowed the recovery from inactivation. AG879 induced a hyperpolarizing shift in the voltage-dependence of the steady-state inactivation of Kv 4.2 channels without apparent effect on the V1/2 of the voltage-dependent activation. The blocking effect of AG879 was enhanced as channel inactivation increased. Furthermore, AG879 significantly inhibited the A-type potassium currents in the cultured hippocampus neurons. AG879 was identified as a selective and potent inhibitor the Kv 4.2 channel. AG879 inhibited Kv 4.2 channels by preferentially interacting with the open state and further accelerating their inactivation. © 2015 The British Pharmacological Society.

The relation of potassium and sodium intakes to diet cost among U.S. adults.

PubMed

Drewnowski, A; Rehm, C D; Maillot, M; Monsivais, P

2015-01-01

The 2010 Dietary Guidelines recommended that Americans increase potassium and decrease sodium intakes to reduce the burden of hypertension. One reason why so few Americans meet the recommended potassium or sodium goals may be perceived or actual food costs. This study explored the monetary costs associated with potassium and sodium intakes using national food prices and a representative sample of US adults. Dietary intake data from the 2001-2002 National Health and Nutrition Examination Survey were merged with a national food prices database. In a population of 4744 adults, the association between the energy-adjusted sodium and potassium intakes, and the sodium-to-potassium ratio (Na:K) and energy-adjusted diet cost was evaluated. Diets that were more potassium-rich or had lower Na:K ratios were associated with higher diet costs, while sodium intakes were not related to cost. The difference in diet cost between extreme quintiles of potassium intakes was $1.49 (95% confidence interval: 1.29, 1.69). A food-level analysis showed that beans, potatoes, coffee, milk, bananas, citrus juices and carrots are frequently consumed and low-cost sources of potassium. Based on existing dietary data and current American eating habits, a potassium-dense diet was associated with higher diet costs, while sodium was not. Price interventions may be an effective approach to improve potassium intakes and reduce the Na:K ratio of the diet. The present methods helped identify some alternative low-cost foods that were effective in increasing potassium intakes. The identification and promotion of lower-cost foods to help individuals meet targeted dietary recommendations could accompany future dietary guidelines.

Calcium-activated potassium channels in insect pacemaker neurons as unexpected target site for the novel fumigant dimethyl disulfide.

PubMed

Gautier, Hélène; Auger, Jacques; Legros, Christian; Lapied, Bruno

2008-01-01

Dimethyl disulfide (DMDS), a plant-derived insecticide, is a promising fumigant as a substitute for methyl bromide. To further understand the mode of action of DMDS, we examined its effect on cockroach octopaminergic neurosecretory cells, called dorsal unpaired median (DUM) neurons, using whole-cell patch-clamp technique, calcium imaging and antisense oligonucleotide strategy. At low concentration (1 microM), DMDS modified spontaneous regular spike discharge into clear bursting activity associated with a decrease of the amplitude of the afterhyperpolarization. This effect led us to suspect alterations of calcium-activated potassium currents (IKCa) and [Ca(2+)](i) changes. We showed that DMDS reduced amplitudes of both peak transient and sustained components of the total potassium current. IKCa was confirmed as a target of DMDS by using iberiotoxin, cadmium chloride, and pSlo antisense oligonucleotide. In addition, we showed that DMDS induced [Ca(2+)](i) rise in Fura-2-loaded DUM neurons. Using calcium-free solution, and (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxy-phenyl)ethyl]-acetamide (LOE 908) [an inhibitor of transient receptor potential (TRP)gamma], we demonstrated that TRPgamma initiated calcium influx. By contrast, omega-conotoxin GVIA (an inhibitor of N-type high-voltage-activated calcium channels), did not affect the DMDS-induced [Ca(2+)](i) rise. Finally, the participation of the calcium-induced calcium release mechanism was investigated using thapsigargin, caffeine, and ryanodine. Our study revealed that DMDS-induced elevation in [Ca(2+)](i) modulated IKCa in an unexpected bell-shaped manner via intracellular calcium. In conclusion, DMDS affects multiple targets, which could be an effective way to improve pest control efficacy of fumigation.

Dietary Approach to Recurrent or Chronic Hyperkalaemia in Patients with Decreased Kidney Function

PubMed Central

Cupisti, Adamasco; Kovesdy, Csaba P.; D’Alessandro, Claudia

2018-01-01

Whereas the adequate intake of potassium is relatively high in healthy adults, i.e., 4.7 g per day, a dietary potassium restriction of usually less than 3 g per day is recommended in the management of patients with reduced kidney function, especially those who tend to develop hyperkalaemia including patients who are treated with angiotensin pathway modulators. Most potassium-rich foods are considered heart-healthy nutrients with high fibre, high anti-oxidant vitamins and high alkali content such as fresh fruits and vegetables; hence, the main challenge of dietary potassium management is to maintain high fibre intake and a low net fixed-acid load, because constipation and metabolic acidosis are per se major risk factors for hyperkalaemia. To achieve a careful reduction of dietary potassium load without a decrease in alkali or fibre intake, we recommend the implementation of certain pragmatic dietary interventions as follows: Improving knowledge and education about the type of foods with excess potassium (per serving or per unit of weight); identifying foods that are needed for healthy nutrition in renal patients; classification of foods based on their potassium content normalized per unit of dietary fibre; education about the use of cooking procedures (such as boiling) in order to achieve effective potassium reduction before eating; and attention to hidden sources of potassium, in particular additives in preserved foods and low-sodium salt substitutes. The present paper aims to review dietary potassium handling and gives information about practical approaches to limit potassium load in chronic kidney disease patients at risk of hyperkalaemia. PMID:29495340

Investigation of new hypergol scrubber technology

NASA Technical Reports Server (NTRS)

Glasscock, Barbara H.

1994-01-01

The ultimate goal of this work is to minimize the liquid waste generated from the scrubbing of hypergolic vent gases. In particular, nitrogen tetroxide, a strong oxidizer used in hypergolic propellant systems, is currently scrubbed with a sodium hydroxide solution resulting in a hazardous liquid waste. This study investigated the use of a solution of potassium hydroxide and hydrogen peroxide for the nitrogen textroxide vent scrubber system. The potassium nitrate formed would be potentially usable as a fertilizer. The hydrogen peroxide is added to convert the potassium nitrite that is formed into more potassium nitrate. Smallscale laboratory tests were conducted to establish the stability of hydrogen peroxide in the proposed scrubbing solution and to evaluate the effectiveness of hydrogen peroxide in converting nitrite to nitrate.

Method for providing uranium articles with a corrosion resistant anodized coating

DOEpatents

Waldrop, Forrest B.; Washington, Charles A.

1982-01-01

Uranium articles are provided with anodized oxide coatings in an aqueous solution of an electrolyte selected from the group consisting of potassium phosphate, potassium hydroxide, ammonium hydroxide, and a mixture of potassium tetraborate and boric acid. The uranium articles are anodized at a temperature greater than about 75.degree. C. with a current flow of less than about 0.036 A/cm.sup.2 of surface area while the pH of the solution is maintained in a range of about 2 to 11.5. The pH values of the aqueous solution and the low current density utilized during the electrolysis prevent excessive dissolution of the uranium and porosity in the film or watering. The relatively high temperature of the electrolyte bath inhibits hydration and the attendant deleterious pitting so as to enhance corrosion resistance of the anodized coating.

Nicotine depresses the functions of multiple cardiac potassium channels.

PubMed

Wang, H; Shi, H; Wang, Z

1999-01-01

Nicotine is the main constituent of tobacco smoke responsible for the elevated risk of the cardiovascular disease and sudden coronary death associated with smoking, presumably by provoking cardiac arrhythmias. The cellular mechanisms may be related to the ability of nicotine to prolong action potentials and to depolarize membrane potential. However, the underlying ionic mechanisms remained unknown. We showed here that nicotine blocked multiple types of K+ currents, including the native currents in canine ventricular myocytes and the cloned channels expressed in Xenopus oocytes: A-type K+ currents (I(to)/Kv4.3), delayed rectifier K+ currents (I(Kr)/HERG) and inward rectifier K+ currents (I(K1)/Kir2.1). Most noticeably, nicotine at a concentration as low as of 10 nM significantly suppressed I(to) and Kv4.3 by approximately 20%. The effects of nicotine were independent of nicotinic receptor simulation or catecholamine release. Our results indicate that nicotine is a non-specific blocker of K+ channels and the inhibitory effects are the consequence of direct interactions between nicotine molecules and the channel proteins. Our study provided for the first time the evidence for the direct inhibition of cardiac K+ channels by nicotine and established a novel aspect of nicotine pharmacology.

Tonic dopamine induces persistent changes in the transient potassium current through translational regulation

PubMed Central

Rodgers, EW; Krenz, W-D; Baro, DJ

2012-01-01

Neuromodulatory effects can vary with their mode of transmission. Phasic release produces local and transient increases in dopamine (DA) up to micromolar concentrations. Additionally, since DA is released from open synapses and reuptake mechanisms are not nearby, tonic nanomolar DA exists in the extracellular space. Do phasic and tonic transmissions similarly regulate voltage dependent ionic conductances in a given neuron? It was previously shown that DA could immediately alter the transient potassium current (IA) of identified neurons in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. Here we show that DA can also persistently alter IA, and that DA’s immediate and persistent effects oppose one another. The lateral pyloric neuron (LP) exclusively expresses type 1 DA receptors (D1Rs). Micromolar DA produces immediate depolarizing shifts in the voltage dependence of LP IA, whereas tonic nanomolar DA produces a persistent increase in LP IA maximal conductance (Gmax) through a translation dependent mechanism involving target of rapamycin (TOR). The pyloric dilator neuron (PD) exclusively expresses type 2 DA receptors (D2Rs). Micromolar DA produces an immediate hyperpolarizing shift in PD IA voltage dependence of activation, whereas tonic DA persistently decreases PD IA Gmax through a translation dependent mechanism not involving TOR. The persistent effects on IA Gmax do not depend on LP or PD activity. These data suggest a role for tonic modulators in the regulation of voltage gated ion channel number; and furthermore, that dopaminergic systems may be organized to limit the amount of change they can impose on a circuit. PMID:21917788

Amoxicillin-potassium clavulanate: a novel beta-lactamase inhibitor.

PubMed

Smith, B R; LeFrock, J L

1985-06-01

Potassium clavulanate is a novel beta-lactamase inhibitor, which, in combination, expands the spectrum of amoxicillin to include many amoxicillin-resistant organisms. Potassium clavulanate is excreted 30-50 percent unchanged renally and its plasma time-course parallels that of amoxicillin. Several studies suggest that an increased incidence of gastrointestinal side effects may occur with this combination. In the current oral formulation, its greatest utility may be in pediatric infections due to beta-lactamase-producing Haemophilus influenzae and B. cattarhalis. In adults, the combination has not been adequately studied against other effective antibiotics.

Accumulation of K+ in the synaptic cleft modulates activity by influencing both vestibular hair cell and calyx afferent in the turtle

PubMed Central

Contini, Donatella; Price, Steven D.

2016-01-01

Key points In the synaptic cleft between type I hair cells and calyceal afferents, K+ ions accumulate as a function of activity, dynamically altering the driving force and permeation through ion channels facing the synaptic cleft.High‐fidelity synaptic transmission is possible due to large conductances that minimize hair cell and afferent time constants in the presence of significant membrane capacitance.Elevated potassium maintains hair cells near a potential where transduction currents are sufficient to depolarize them to voltages necessary for calcium influx and synaptic vesicle fusion.Elevated potassium depolarizes the postsynaptic afferent by altering ion permeation through hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels, and contributes to depolarizing the afferent to potentials where a single EPSP (quantum) can generate an action potential.With increased stimulation, hair cell depolarization increases the frequency of quanta released, elevates [K+]cleft and depolarizes the afferent to potentials at which smaller and smaller EPSPs would be sufficient to trigger APs. Abstract Fast neurotransmitters act in conjunction with slower modulatory effectors that accumulate in restricted synaptic spaces found at giant synapses such as the calyceal endings in the auditory and vestibular systems. Here, we used dual patch‐clamp recordings from turtle vestibular hair cells and their afferent neurons to show that potassium ions accumulating in the synaptic cleft modulated membrane potentials and extended the range of information transfer. High‐fidelity synaptic transmission was possible due to large conductances that minimized hair cell and afferent time constants in the presence of significant membrane capacitance. Increased potassium concentration in the cleft maintained the hair cell near potentials that promoted the influx of calcium necessary for synaptic vesicle fusion. The elevated potassium concentration also depolarized the postsynaptic neuron by altering ion permeation through hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels. This depolarization enabled the afferent to reliably generate action potentials evoked by single AMPA‐dependent EPSPs. Depolarization of the postsynaptic afferent could also elevate potassium in the synaptic cleft, and would depolarize other hair cells enveloped by the same neuritic process increasing the fidelity of neurotransmission at those synapses as well. Collectively, these data demonstrate that neuronal activity gives rise to potassium accumulation, and suggest that potassium ion action on HCN channels can modulate neurotransmission, preserving the fidelity of high‐speed synaptic transmission by dynamically shifting the resting potentials of both presynaptic and postsynaptic cells. PMID:27633787

Depolarization of the Internal Membrane System in the Activation of Frog Skeletal Muscle

PubMed Central

Costantin, L. L.; Podolsky, R. J.

1967-01-01

"Skinned" muscle fibers, single fibers from the frog semitendinosus muscle in which the sarcolemma had been removed, could be reversibly activated by electrical stimulation. Electrical responsiveness was abolished when the skinned fiber was prepared from a muscle exposed to a cardiac glycoside, and the development of responsiveness was delayed when the muscle was bathed in high potassium solution. The findings were taken as evidence that active sodium-potassium exchange across the internal membranes restored electrical excitability, after the sarcolemma had been removed, by establishing a potential gradient across the internal membranes. In general, the contractions were graded with the strength of the applied current. On occasion, however, "all-or-none" type responses were seen, raising the possibility that the internal membranes were capable of an electrically regenerative response. Activation could also be produced by an elevation of the intracellular chloride ion concentration or a decrease in the intracellular potassium, ion concentration, suggesting that depolarization of some element of the internal membrane system, that is, a decrease in the potential of the lumen of the internal membrane system relative to the potential of the myofibrillar space, was responsible for activation in these experiments. The distribution of both the electrically induced contractions and those produced by changes in the intracellular ion concentrations indicated that the responsive element of the internal membrane system was electrically continuous over many sarcomeres. PMID:6033576

Estrogens and human papilloma virus oncogenes regulate human ether-à-go-go-1 potassium channel expression.

PubMed

Díaz, Lorenza; Ceja-Ochoa, Irais; Restrepo-Angulo, Iván; Larrea, Fernando; Avila-Chávez, Euclides; García-Becerra, Rocío; Borja-Cacho, Elizabeth; Barrera, David; Ahumada, Elías; Gariglio, Patricio; Alvarez-Rios, Elizabeth; Ocadiz-Delgado, Rodolfo; Garcia-Villa, Enrique; Hernández-Gallegos, Elizabeth; Camacho-Arroyo, Ignacio; Morales, Angélica; Ordaz-Rosado, David; García-Latorre, Ethel; Escamilla, Juan; Sánchez-Peña, Luz Carmen; Saqui-Salces, Milena; Gamboa-Dominguez, Armando; Vera, Eunice; Uribe-Ramírez, Marisela; Murbartián, Janet; Ortiz, Cindy Sharon; Rivera-Guevara, Claudia; De Vizcaya-Ruiz, Andrea; Camacho, Javier

2009-04-15

Ether-à-go-go-1 (Eag1) potassium channels are potential tools for detection and therapy of numerous cancers. Here, we show human Eag1 (hEag1) regulation by cancer-associated factors. We studied hEag1 gene expression and its regulation by estradiol, antiestrogens, and human papillomavirus (HPV) oncogenes (E6/E7). Primary cultures from normal placentas and cervical cancer tissues; tumor cell lines from cervix, choriocarcinoma, keratinocytes, and lung; and normal cell lines from vascular endothelium, keratinocytes, and lung were used. Reverse transcription-PCR (RT-PCR) experiments and Southern blot analysis showed Eag1 expression in all of the cancer cell types, normal trophoblasts, and vascular endothelium, in contrast to normal keratinocytes and lung cells. Estradiol and antiestrogens regulated Eag1 in a cell type-dependent manner. Real-time RT-PCR experiments in HeLa cells showed that Eag1 estrogenic regulation was strongly associated with the expression of estrogen receptor-alpha. Eag1 protein was detected by monoclonal antibodies in normal placenta and placental blood vessels. Patch-clamp recordings in normal trophoblasts treated with estradiol exhibited potassium currents resembling Eag1 channel activity. Eag1 gene expression in keratinocytes depended either on cellular immortalization or the presence of HPV oncogenes. Eag1 protein was found in keratinocytes transfected with E6/E7 HPV oncogenes. Cell proliferation of E6/E7 keratinocytes was decreased by Eag1 antibodies inhibiting channel activity and by the nonspecific Eag1 inhibitors imipramine and astemizole; the latter also increased apoptosis. Our results propose novel oncogenic mechanisms of estrogen/antiestrogen use and HPV infection. We also suggest Eag1 as an early indicator of cell proliferation leading to malignancies and a therapeutic target at early stages of cellular hyperproliferation.

Vertebrate rod photoreceptors express both BK and IK calcium-activated potassium channels, but only BK channels are involved in receptor potential regulation.

PubMed

Pelucchi, Bruna; Grimaldi, Annalisa; Moriondo, Andrea

2008-01-01

In salamander rods, Ca(2+)-activated K(+) current (I(KCa)) provides an effective "clamp" of the dark membrane potential to its normal resting level. By a combination of electrophysiological, pharmacological, and immunohistochemical approaches, we show that salamander rods functionally express large-conductance Ca(2+)- and voltage-dependent potassium (BK) channel and intermediate-conductance Ca(2+)-dependent potassium (IK) channel, but not small-conductance Ca(2+)-dependent potassium channel (SK) subtypes. Application of 100 nM iberiotoxin and 100 nM clotrimazole reduced net I(KCa) to 36% and 63%, respectively, whereas the current was unaffected by application of 1 microM apamin. Consistently, anti- SK1, -SK2, and -SK3 antibodies were unable to stain rod photoreceptors, whereas both anti-BK and -SK4/ IK1 antibodies heavily stained the ellipsoid region of the inner segments of the rods. Moreover, by using current-clamp experiments, it was clearly seen that the strong clamping effect of the total I(KCa) was lost when IbTx, but not CLTZ, was applied to the bath. This behavior strongly suggests that of BK and IK channels, only the former are responsible for the clamping effect on the photoreceptor membrane potential.

Phase Segregation in Potassium-Doped Lead Halide Perovskites from 39K Solid-State NMR at 21.1 T.

PubMed

Kubicki, Dominik J; Prochowicz, Daniel; Hofstetter, Albert; Zakeeruddin, Shaik M; Grätzel, Michael; Emsley, Lyndon

2018-06-13

Organic-inorganic lead halide perovskites are a promising family of light absorbers for a new generation of solar cells, with reported efficiencies currently exceeding 22%. A common problem of solar cells fabricated using these materials is that their efficiency depends on their cycling history, an effect known as current-voltage ( J- V) hysteresis. Potassium doping has recently emerged as a universal way to overcome this adverse phenomenon. While the atomistic origins of J- V hysteresis are still not fully understood, it is essential to rationalize the atomic-level effect of protocols that lead to its suppression. Here, using 39 K MAS NMR at 21.1 T we provide for the first time atomic-level characterization of the potassium-containing phases that are formed upon KI doping of multication and multianion lead halide perovskites. We find no evidence of potassium incorporation into 3D perovskite lattices of the recently reported materials. Instead, we observe formation of a mixture of potassium-rich phases and unreacted KI. In the case of Br-containing lead halide perovskites doped with KI, a mixture of KI and KBr ensues, leading to a change in the Br/I ratio in the perovskite phase with respect to the undoped perovskite. Simultaneous Cs and K doping leads to the formation of nonperovskite Cs/K lead iodide phases.

Crystal Structure of the Potassium Importing KdpFABC Membrane Complex

PubMed Central

Huang, Ching-Shin; Pedersen, Bjørn Panyella; Stokes, David Lloyd

2017-01-01

Cellular potassium import systems play a fundamental role in osmoregulation, pH homeostasis and membrane potential in all domains of life. In bacteria, the kdp operon encodes a four subunit potassium pump that maintains intracellular homeostasis as well as cell shape and turgor under conditions where potassium is limiting1. This membrane complex, called KdpFABC, has one channel-like subunit (KdpA) belonging to the Superfamily of Potassium Transporters and another pump-like subunit (KdpB) belonging to the Superfamily of P-type ATPases. Although there is considerable structural and functional information about members from both superfamilies, the mechanism by which uphill potassium transport through KdpA is coupled with ATP hydrolysis by KdpB remains poorly understood. Here we report the 2.9 Å X-ray structure of the complete Escherichia coli KdpFABC complex with a potassium ion within the selectivity filter of KdpA as well as a water molecule at a canonical cation site in the transmembrane domain of KdpB. The structure also reveals two structural elements that appear to mediate the coupling between these two subunits. Specifically, a protein-embedded tunnel runs between these potassium and water sites and a helix controlling the cytoplasmic gate of KdpA is linked to the phosphorylation domain of KdpB. Based on these observations, we propose an unprecedented mechanism that repurposes protein channel architecture for active transport across biomembranes. PMID:28636601

Potential New Agents for the Management of Hyperkalemia.

PubMed

Packham, David K; Kosiborod, Mikhail

2016-02-01

Hyperkalemia is a common electrolyte disturbance with multiple potential etiologies. It is usually observed in the setting of reduced renal function. Mild to moderate hyperkalemia is usually asymptomatic, but is associated with poor prognosis. When severe, hyperkalemia may cause serious acute cardiac arrhythmias and conduction abnormalities, and may result in sudden death. The rising prevalence of conditions associated with hyperkalemia (heart failure, chronic kidney disease, and diabetes) and broad use of renin-angiotensin-aldosterone system (RAAS) inhibitors and mineralocorticoid receptor antagonists (MRAs), which improve patient outcomes but increase the risk of hyperkalemia, have led to a significant rise in hyperkalemia-related hospitalizations and deaths. Current non-invasive therapies for hyperkalemia either do not remove excess potassium or have poor efficacy and tolerability. There is a clear need for safer, more effective potassium-lowering therapies suitable for both acute and chronic settings. Patiromer sorbitex calcium and sodium zirconium cyclosilicate (ZS-9) are two new potassium-lowering compounds currently in development. Although they have not yet been approved by the US FDA, both have demonstrated efficacy and safety in recent trials. Patiromer sorbitex calcium is a polymer resin and sorbitol complex that binds potassium in exchange for calcium; ZS-9, a non-absorbed, highly selective inorganic cation exchanger, traps potassium in exchange for sodium and hydrogen. This review discusses the merits of both novel drugs and how they may help optimize the future management of patients with hyperkalemia.

Evaluation of eddy-current proximity devices for measuring thin potassium film thicknesses

NASA Technical Reports Server (NTRS)

Asadourian, A. S.

1972-01-01

Two eddy current proximity probe systems were tested over a range of 0 to 508 micrometers (0 to 20 mils) of simulated potassium film thicknesses for simulated temperatures of 66 C (150 F), 232 C (450 F), and 666 C (1230 F). The results of short time calibration tests are presented. Instrument drift was a problem throughout the testing and, without correction, may limit the use of such systems to short periods of time. Additional development will be required prior to their being usable as practical instrumentation systems.

Synaptic calcium regulation in hair cells of the chicken basilar papilla.

PubMed

Im, Gi Jung; Moskowitz, Howard S; Lehar, Mohammed; Hiel, Hakim; Fuchs, Paul Albert

2014-12-10

Cholinergic inhibition of hair cells occurs by activation of calcium-dependent potassium channels. A near-membrane postsynaptic cistern has been proposed to serve as a store from which calcium is released to supplement influx through the ionotropic ACh receptor. However, the time and voltage dependence of acetylcholine (ACh)-evoked potassium currents reveal a more complex relationship between calcium entry and release from stores. The present work uses voltage steps to regulate calcium influx during the application of ACh to hair cells in the chicken basilar papilla. When calcium influx was terminated at positive membrane potential, the ACh-evoked potassium current decayed exponentially over ∼100 ms. However, at negative membrane potentials, this current exhibited a secondary rise in amplitude that could be eliminated by dihydropyridine block of the voltage-gated calcium channels of the hair cell. Calcium entering through voltage-gated channels may transit through the postsynaptic cistern, since ryanodine and sarcoendoplasmic reticulum calcium-ATPase blockers altered the time course and magnitude of this secondary, voltage-dependent contribution to ACh-evoked potassium current. Serial section electron microscopy showed that efferent and afferent synaptic structures are juxtaposed, supporting the possibility that voltage-gated influx at afferent ribbon synapses influences calcium homeostasis during long-lasting cholinergic inhibition. In contrast, spontaneous postsynaptic currents ("minis") resulting from stochastic efferent release of ACh were made briefer by ryanodine, supporting the hypothesis that the synaptic cistern serves primarily as a calcium barrier and sink during low-level synaptic activity. Hypolemmal cisterns such as that at the efferent synapse of the hair cell can play a dynamic role in segregating near-membrane calcium for short-term and long-term signaling. Copyright © 2014 the authors 0270-6474/14/3416688-10$15.00/0.

Synaptic Calcium Regulation in Hair Cells of the Chicken Basilar Papilla

PubMed Central

Im, Gi Jung; Moskowitz, Howard S.; Lehar, Mohammed; Hiel, Hakim

2014-01-01

Cholinergic inhibition of hair cells occurs by activation of calcium-dependent potassium channels. A near-membrane postsynaptic cistern has been proposed to serve as a store from which calcium is released to supplement influx through the ionotropic ACh receptor. However, the time and voltage dependence of acetylcholine (ACh)-evoked potassium currents reveal a more complex relationship between calcium entry and release from stores. The present work uses voltage steps to regulate calcium influx during the application of ACh to hair cells in the chicken basilar papilla. When calcium influx was terminated at positive membrane potential, the ACh-evoked potassium current decayed exponentially over ∼100 ms. However, at negative membrane potentials, this current exhibited a secondary rise in amplitude that could be eliminated by dihydropyridine block of the voltage-gated calcium channels of the hair cell. Calcium entering through voltage-gated channels may transit through the postsynaptic cistern, since ryanodine and sarcoendoplasmic reticulum calcium-ATPase blockers altered the time course and magnitude of this secondary, voltage-dependent contribution to ACh-evoked potassium current. Serial section electron microscopy showed that efferent and afferent synaptic structures are juxtaposed, supporting the possibility that voltage-gated influx at afferent ribbon synapses influences calcium homeostasis during long-lasting cholinergic inhibition. In contrast, spontaneous postsynaptic currents (“minis”) resulting from stochastic efferent release of ACh were made briefer by ryanodine, supporting the hypothesis that the synaptic cistern serves primarily as a calcium barrier and sink during low-level synaptic activity. Hypolemmal cisterns such as that at the efferent synapse of the hair cell can play a dynamic role in segregating near-membrane calcium for short-term and long-term signaling. PMID:25505321

[Effect of substance P on the potassium and calcium currents of colonic smooth muscle cells].

PubMed

Tang, Qincai; Luo, Hesheng; Quan, Xiaojing; Fan, Han; Yu, Guang

2015-08-11

To investigate the effect of substance P(SP) on the spontaneous contractile activity of smooth muscle cells,the large-conductance calcium-activated potassium channel currents (IBKCa) and the L-type calcium channel currents (ICaL) in rat smooth muscle cells of the proximal colon. A total of 24 healthy male Wista rats were used in this test. The change of smooth muscle strips spontaneous contraction of rat proximal colon after adding SP was recorded by a physiological signal stystem (RM6240). The IBKCa and ICaL were measured via the whole cell patch-clamp technique. The longitudinal muscle contraction was obviously increased concentration-dependently after adding different concentrations of SP (10(-7)-10(-6) mol/L), so as the circular muscle while adding SP(10(-8)-10(-6) mol/L) (all P<0.05). Compared with the control group, IBKCa was decreased after adding SP(10(-6) mol/L). Under the stimulating voltage of 60 mV, the IBKCa current density was (11.71±1.65) pA/pF, which was significantly lower compared with the control group (14.42±2.89) pA/pF (P<0.05). The ICaL) was apparently increased. Under the stimulating voltage of 0 mV, the ICaL) currents density was (-5.04±0.67) pA/pF, compared with the control group (-4.25±0.46) pA/pF, which was significantly increased (P<0.01). SP can promote the spontaneous contractile activity of colon smooth muscle of rats in vitro.And SP decrease IBKCa representatively while apparently increase ICaL). That is probably one of the mechanism SP regulate the gastrointestinal motility.

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

PubMed

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.

Gastrodin Inhibits Allodynia and Hyperalgesia in Painful Diabetic Neuropathy Rats by Decreasing Excitability of Nociceptive Primary Sensory Neurons

PubMed Central

Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

2012-01-01

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients’ quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I NaT) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I NaT and a decrease of potassium currents, especially slowly inactivating potassium currents (I AS); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I NaT and total potassium current as well as I AS currents induced by STZ were normalized by GAS. This study provides a clear cellular basis for the peripheral analgesic action of gastrodin for the treatment of chronic pain, including PDN. PMID:22761855

Low serum potassium level is associated with nonalcoholic fatty liver disease and its related metabolic disorders.

PubMed

Sun, Kan; Lu, Jieli; Jiang, Yiran; Xu, Min; Xu, Yu; Zhang, Jie; Xu, Baihui; Sun, Jichao; Sun, Wanwan; Ren, Chenxi; Liu, Jianmin; Wang, Weiqing; Bi, Yufang; Ning, Guang

2014-03-01

Subjects with nonalcoholic fatty liver disease (NAFLD) have a high risk of developing type 2 diabetes and cardiovascular diseases. Low serum potassium concentration or low dietary potassium intake can result in metabolic disorders. Our objective was to evaluate the association between low serum potassium level and prevalence of NAFLD in a Chinese population. A population-based cross-sectional study. We conducted a community-based study in 8592 subjects to investigate the association of serum potassium with the risk of prevalent NAFLD. NAFLD was diagnosed by hepatic ultrasonography. The prevalence rate of NAFLD was 30·3% in this population and gradually decreased across serum potassium quartiles. With the reduction in serum potassium level, participants have larger waist circumference (WC) and more severe insulin resistance. The correlations hold also in multivariate linear regression analysis. In logistic regression analysis, compared with subjects in the highest quartile of serum potassium level, the adjusted odds ratios (ORs) in the lowest quartile was 1·33 [95% confidence interval (CI), 1·11-1·60] for NAFLD, 1·81 (95% CI, 1·49-2·19) for insulin resistance and 1·58 (95% CI, 1·30-1·93) for central obesity. In subgroup analysis after multiple adjustments, significant relation between serum potassium level and prevalent NAFLD was detected in women, younger subjects, those with insulin resistance and those with central obesity, respectively. Low serum potassium level significantly associated with prevalence of NAFLD in middle-aged and elderly Chinese. © 2013 John Wiley & Sons Ltd.

Countercurrent Chromatographic Separation of Proteins Using an Eccentric Coiled Column with Synchronous and Nonsynchronous Type-J Planetary Motions

PubMed Central

SHINOMIYA, Kazufusa; YOSHIDA, Kazunori; TOKURA, Koji; TSUKIDATE, Etsuhiro; YANAGIDAIRA, Kazuhiro; ITO, Yoichiro

2015-01-01

Protein separation was performed using the high-speed counter-current chromatograph (HSCCC) at both synchronous and nonsynchronous type-J planetary motions. The partition efficiency was evaluated with two different column configurations, eccentric coil and toroidal coil, on the separation of a set of stable protein samples including cytochrome C, myoglobin and lysozyme with a polymer phase system composed of 12.5% (w/w) polyethylene glycol 1000 and 12.5% (w/w) dibasic potassium phosphate. Better peak resolution was obtained by the eccentric coil than by the toroidal coil using either lower or upper phase as the mobile phase. The peak resolution was further improved using the eccentric coil by the nonsynchronous type-J planetary motion with the combination of 1066 rpm of column rotation and 1000 rpm of revolution. PMID:25765276

Atrial cellular electrophysiological changes in patients with ventricular dysfunction may predispose to AF

PubMed Central

Workman, Antony J; Pau, Davide; Redpath, Calum J; Marshall, Gillian E; Russell, Julie A; Norrie, John; Kane, Kathleen A; Rankin, Andrew C

2009-01-01

Background Left ventricular systolic dysfunction (LVSD) is a risk factor for atrial fibrillation (AF), but the atrial cellular electrophysiological mechanisms in humans are unclear. Objective To investigate whether LVSD in patients who are in sinus rhythm (SR) is associated with atrial cellular electrophysiological changes which could predispose to AF. Methods Right atrial myocytes were obtained from 214 consenting patients in SR who were undergoing cardiac surgery. Action potentials or ion currents were measured using the whole-cell-patch clamp technique. Results The presence of moderate or severe LVSD was associated with a shortened atrial cellular effective refractory period, ERP (209±8 ms; 52 cells, 18 patients vs 233±7 ms; 134 cells, 49 patients; P<0.05); confirmed by multiple linear regression analysis. The LV ejection fraction (LVEF) was markedly lower in patients with moderate or severe LVSD (36±4%, n=15) than in those without LVSD (62±2%, n=31; P<0.05). In cells from patients with LVEF≤45%, the ERP and action potential duration at 90% repolarisation were shorter than in those from patients with LVEF>45%, by 24 and 18%, respectively. The LVEF and ERP were positively correlated (r=0.65, P<0.05). The L-type calcium ion current, inward rectifier potassium ion current, and sustained outward ion current was unaffected by LVSD. The transient outward potassium ion current was decreased by 34%, with a positive shift in its activation voltage, and no change in its decay kinetics. Conclusion LVSD in patients in SR is independently associated with a shortening of the atrial cellular ERP, which may be expected to contribute to a predisposition to AF. PMID:19324301

Functional analysis of potassium channels in Kv7.2 G271V mutant causing early onset familial epilepsy.

PubMed

Wang, Juanjuan; Li, Yuan; Hui, Zhiyan; Cao, Min; Shi, Ruiming; Zhang, Wei; Geng, Limeng; Zhou, Xihui

2015-08-07

Kv7 (KCNQ) channels underlying a class of voltage-gated K+ current are best known for regulating neuronal excitability. The first glycine (G) residue in the pore helix of Kv7.2 (KCNQ2) subunit is highly conserved among different classes of Kv7 channel family. A missense mutation causing the replacement of the corresponding G residues with a valine (p.G271V) in Kv7.2 was found in a large, four-generation pedigree. Here, we set out to examine the molecular pathomechanism of G271V mutants using patch clamp technology combined with biochemical and immunocytochemical techniques in transiently transfected human embryonic kidney (HEK) 293 cells. The expression of Kv7.2 protein had the same intensity for both wild type (WT) and G271V. In transfected HEK cells, G271V mutants induced large depolarizing shifts of the conductance-voltage relationships and marked slowing of current activation kinetics compared to WT. In addition, G271V mutants abolished currents in homomeric channels, and resulted in about 50% reduction of current in Kv7.2/G271V/Kv7.3 heteromultimeric condition, indicating a more severe functional defect. To test for G271V mutant channel expression in surface membrane, we performed fluorescence confocal microscopy imaging, which revealed no differences between the mutant and WT, suggesting that G271V channels fail to open in response to depolarization even though they are present in the membrane. Furthermore, pharmacologic intervention experiments revealed that upon specific incubation of transfected HEK 293 cells expressing G271V heteromultimeric channels in presence of Kv7 channel enhancer retigabine (ezogabine), the potassium currents increased significantly, suggesting the potential of retigabine as gene-specific therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Method for providing uranium articles with a corrosion-resistant anodized coating

DOEpatents

Waldrop, F.B.; Washington, C.A.

1981-01-07

Uranium articles are provided with anodized oxide coatings in an aqueous solution of an electrolyte selected from the group consisting of potassium phosphate, potassium hydroxide, ammonium hydroxide, and a mixture of potassium tetraborate and boric acid. The uranium articles are anodized at a temperature greater than about 75/sup 0/C with a current flow of less than about 0.036 A/cm/sup 2/ of surface area while the pH of the solution is maintained in a range of about 2 to 11.5. The pH values of the aqueous solution and the low current density utilized during the electrolysis prevent excessive dissolution of the uranium and porosity in the film or watering. The relatively high temperature of the electrolyte bath inhibits hydration and the attendant deleterious pitting so as to enhance corrosion resistance of the anodized coating.

Diabetic ketoacidosis producing extreme hyperkalemia in a patient with type 1 diabetes on hemodialysis.

PubMed

Yamada, Hodaka; Funazaki, Shunsuke; Kakei, Masafumi; Hara, Kazuo; Ishikawa, San-E

2017-01-01

Diabetic ketoacidosis (DKA) is a critical complication of type 1 diabetes associated with water and electrolyte disorders. Here, we report a case of DKA with extreme hyperkalemia (9.0 mEq/L) in a patient with type 1 diabetes on hemodialysis. He had a left frontal cerebral infarction resulting in inability to manage his continuous subcutaneous insulin infusion pump. Electrocardiography showed typical changes of hyperkalemia, including absent P waves, prolonged QRS interval and tented T waves. There was no evidence of total body water deficit. After starting insulin and rapid hemodialysis, the serum potassium level was normalized. Although DKA may present with hypokalemia, rapid hemodialysis may be necessary to resolve severe hyperkalemia in a patient with renal failure. Patients with type 1 diabetes on hemodialysis may develop ketoacidosis because of discontinuation of insulin treatment.Patients on hemodialysis who develop ketoacidosis may have hyperkalemia because of anuria.Absolute insulin deficit alters potassium distribution between the intracellular and extracellular space, and anuria abolishes urinary excretion of potassium.Rapid hemodialysis along with intensive insulin therapy can improve hyperkalemia, while fluid infusions may worsen heart failure in patients with ketoacidosis who routinely require hemodialysis.

Properties of the cromakalim-induced potassium conductance in smooth muscle cells isolated from the rabbit portal vein.

PubMed Central

Beech, D. J.; Bolton, T. B.

1989-01-01

1. Single smooth muscle cells were isolated freshly from the rabbit portal vein and membrane currents were recorded by the whole-cell or excised patch configurations of the patch-clamp technique at room temperature. 2. Cromakalim (Ckm, 10 microM) induced a potassium current (ICkm) that showed no pronounced voltage-dependence and had low current noise. 3. This current, ICkm, was inhibited by (in order of potency): phencyclidine greater than quinidine greater than 4-aminopyridine greater than tetraethylammonium ions (TEA). These drugs inhibited the delayed rectifier current, IdK, which is activated by depolarization of the cell, with the same order of potency. 4. Large conductance calcium-activated potassium channels (LKCa) in isolated membrane patches were blocked by (in order of potency) quinidine greater than TEA approximately phencyclidine. 4-Aminopyridine was ineffective. A similar order of potency was found for block of spontaneous transient outward currents thought to represent bursts of openings of LKCa channels. 5. The low current noise of ICkm at positive potentials, and its susceptibility to inhibitors indicated that it was not carried by LKCa channels, and that it may be carried by channels which underlie IdK. It was observed that when ICkm was activated, IdK was reduced. However, in two experiments, ICkm was much more susceptible to glibenclamide than IdK; possible reasons for this are discussed. PMID:2590772

78 FR 40695 - Persulfates From the People's Republic of China: Final Results of Expedited Third Sunset Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

..., potassium, and sodium persulfates. The chemical formula for these persulfates are, respectively, (NH 4 ) 2 S 2 O 8 , K 2 S 2 O 8 , and Na 2 S 2 O 8 . Potassium persulfates are currently classifiable under...

Control of Phasic Firing by a Background Leak Current in Avian Forebrain Auditory Neurons

PubMed Central

Dagostin, André A.; Lovell, Peter V.; Hilscher, Markus M.; Mello, Claudio V.; Leão, Ricardo M.

2015-01-01

Central neurons express a variety of neuronal types and ion channels that promote firing heterogeneity among their distinct neuronal populations. Action potential (AP) phasic firing, produced by low-threshold voltage-activated potassium currents (VAKCs), is commonly observed in mammalian brainstem neurons involved in the processing of temporal properties of the acoustic information. The avian caudomedial nidopallium (NCM) is an auditory area analogous to portions of the mammalian auditory cortex that is involved in the perceptual discrimination and memorization of birdsong and shows complex responses to auditory stimuli We performed in vitro whole-cell patch-clamp recordings in brain slices from adult zebra finches (Taeniopygia guttata) and observed that half of NCM neurons fire APs phasically in response to membrane depolarizations, while the rest fire transiently or tonically. Phasic neurons fired APs faster and with more temporal precision than tonic and transient neurons. These neurons had similar membrane resting potentials, but phasic neurons had lower membrane input resistance and time constant. Surprisingly phasic neurons did not express low-threshold VAKCs, which curtailed firing in phasic mammalian brainstem neurons, having similar VAKCs to other NCM neurons. The phasic firing was determined not by VAKCs, but by the potassium background leak conductances, which was more prominently expressed in phasic neurons, a result corroborated by pharmacological, dynamic-clamp, and modeling experiments. These results reveal a new role for leak currents in generating firing diversity in central neurons. PMID:26696830

The changes of potassium currents in rabbit ventricle with healed myocardial infarction.

PubMed

Liu, Nian; Niu, Huiyan; Li, Yang; Zhang, Cuntai; Zhou, Qiang; Ruan, Yanfei; Pu, Jun; Lu, Zaiying

2004-01-01

To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (Ito), delayed rectifier potassium current (IK) and inward rectifier potassium current (IK1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, Ito, IK, and IK1 of ventricular myocytes in non-infarcted zone. Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of Ito, I(K, tail), and IK1 were reduced significantly in HMI group, from 6.72 +/- 0.42 pA/pF, 1.54 +/- 0.13 pA/pF and 25.6 +/- 2.6 pA/pF in sham-operated group to 4.03 +/- 0.33 pA/pF, 1.14 +/- 0.11 pA/pF and 17.6 +/- 2.3 pA/pF, respectively. It is concluded that the reduced densities of Ito, I(K, tail) and IK1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.

Reduction of electron accumulation at InN(0001) surfaces via saturation of surface states by potassium and oxygen as donor- or acceptor-type adsorbates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eisenhardt, A.; Reiß, S.; Krischok, S., E-mail: stefan.krischok@tu-ilmenau.de

2014-01-28

The influence of selected donor- and acceptor-type adsorbates on the electronic properties of InN(0001) surfaces is investigated implementing in-situ photoelectron spectroscopy. The changes in work function, surface band alignment, and chemical bond configurations are characterized during deposition of potassium and exposure to oxygen. Although an expected opponent charge transfer characteristic is observed with potassium donating its free electron to InN, while dissociated oxygen species extract partial charge from the substrate, a reduction of the surface electron accumulation occurs in both cases. This observation can be explained by adsorbate-induced saturation of free dangling bonds at the InN resulting in the disappearancemore » of surface states, which initially pin the Fermi level and induce downward band bending.« less

Dietary salt consumption and the knowledge, attitudes and behavior of healthy adults: a cross-sectional study from Jordan.

PubMed

Alawwa, Izzat; Dagash, Rajaa; Saleh, Akram; Ahmad, Abdelaziz

2018-12-01

High dietary sodium is recognized as a silent killer responsible for 2.3 million deaths worldwide in 2010 predominantly secondary to hypertension and its complications. Although high salt consumption is considered a worldwide public health problem, its magnitude is highly variable among different communities; therefore, it is important to study locally. This study aimed to evaluate habitual salt consumption, its important correlations, as well as the knowledge, attitude, and behavior of healthy Jordanian citizens. As potassium consumption is highly correlated and important we aimed to study both jointly. In this descriptive cross-sectional study we enrolled 103 healthy adult Jordanian citizens. All participants were interviewed for questionnaire filling, physical examination, and instructed on proper 24-hour urine collection procedure. We measured sodium and potassium concentration in the provided controlled 24-hour urine collection samples, as it is presently considered the gold standard for evaluating daily intake. The results showed an average sodium intake of 179 mmol (4.1 g) per day [higher in males at 186 mmol (4.3 g) vs. 173 mmol (4.0 g) for females], significantly above the current WHO recommendations, though only 8% regularly add salt to food. Ironically, most participants (82%) believe their salt consumption was appropriate and only 29% thought they may benefit from reducing salt intake. On the other hand, potassium intake is far below the current WHO recommendations. High sodium and low potassium intake have synergistic adverse effects on public health that is not currently addressed in Jordan. We conclude that Jordanian citizens currently consume high sodium and low potassium diet and are mostly unaware of its negative impact on their health. Hence, it is crucial for healthcare providers to intervene and adopt long-term strategies to control salt intake to reduce its negative effects in Jordan and elsewhere.

Functional role of A-type potassium currents in rat presympathetic PVN neurones

PubMed Central

Sonner, Patrick M; Stern, Javier E

2007-01-01

Despite the fact that paraventricular nucleus (PVN) neurones innervating the rostral ventrolateral medulla (RVLM) play important roles in the control of sympathetic function both in physiological and pathological conditions, the precise mechanisms controlling their activity are still incompletely understood. In the present study, we evaluated whether the transient outward potassium current IA is expressed in PVN-RVLM neurones, characterized its biophysical and pharmacological properties, and determined its role in shaping action potentials and firing discharge in these neurones. Patch-clamp recordings obtained from retrogradely labelled, PVN-RVLM neurones indicate that a 4-AP sensitive, TEA insensitive current, with biophysical properties consistent with IA, is present in these neurones. Pharmacological blockade of IA depolarized resting Vm and prolonged Na+ action potential duration, by increasing its width and by slowing down its decay time course. Interestingly, blockade of IA either increased or decreased the firing activity of PVN-RVLM neurones, supporting the presence of subsets of PVN-RVLM neurones differentially modulated by IA. In all cases, the effects of IA on firing activity were prevented by a broad spectrum Ca2+ channel blocker. Immunohistochemical studies suggest that IA in PVN-RVLM neurons is mediated by Kv1.4 and/or Kv4.3 channel subunits. Overall, our results demonstrate the presence of IA in PVN-RVLM neurones, which actively modulates their action potential waveform and firing activity. These studies support IA as an important intrinsic mechanism controlling neuronal excitability in this central presympathetic neuronal population. PMID:17525115

Monitoring of urea and potassium by reverse iontophoresis in vitro.

PubMed

Wascotte, Valentine; Delgado-Charro, M Begoña; Rozet, Eric; Wallemacq, Pierre; Hubert, Philippe; Guy, Richard H; Préat, Véronique

2007-06-01

Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined. In vitro experiments were performed to test (a) a series of subdermal urea and potassium concentrations typical of the pathophysiologic range, and (b) a decreasing profile of urea and potassium subdermal concentrations to mimic those which are observed during hemodialysis. (a) After 60-120 min of iontophoresis, linear relationships (p < 0.05) were established between both urea and potassium fluxes and their respective subdermal concentrations. The determination coefficients were above 0.9 after 1 h of current passage using sodium as an internal standard. (b) Reverse iontophoretic fluxes of urea and K(+) closely paralleled the decay of the respective concentrations in the subdermal compartment, as would occur during a hemodialysis session. These in vitro experiments demonstrate that urea and potassium can be quantitatively and proportionately extracted by reverse iontophoresis, even when the subdermal concentrations of the analytes are varying with time. These results suggest the non-invasive monitoring of urea and potassium to diagnose renal failure and during hemodialysis is feasible, and that in vivo measurements are warranted.

Reference Atmosphere for Mercury

NASA Technical Reports Server (NTRS)

Killen, Rosemary M.

2002-01-01

We propose that Ar-40 measured in the lunar atmosphere and that in Mercury's atmosphere is due to current diffusion into connected pore space within the crust. Higher temperatures at Mercury, along with more rapid loss from the atmosphere will lead to a smaller column abundance of argon at Mercury than at the Moon, given the same crustal abundance of potassium. Because the noble gas abundance in the Hermean atmosphere represents current effusion, it is a direct measure of the crustal potassium abundance. Ar-40 in the atmospheres of the planets is a measure of potassium abundance in the interiors, since Ar-40 is a product of radiogenic decay of K-40 by electron capture with the subsequent emission of a 1.46 eV gamma-ray. Although the Ar-40 in the Earth's atmosphere is expected to have accumulated since the late bombardment, Ar-40 in the atmospheres of Mercury and the Moon is eroded quickly by photoionization and electron impact ionization. Thus, the argon content in the exospheres of the Moon and Mercury is representative of current effusion rather than accumulation over the lifetime of the planet.

Sodium-to-Potassium Ratio and Blood Pressure, Hypertension, and Related Factors12

PubMed Central

Perez, Vanessa; Chang, Ellen T.

2014-01-01

The potential cost-effectiveness and feasibility of dietary interventions aimed at reducing hypertension risk are of considerable interest and significance in public health. In particular, the effectiveness of restricted sodium or increased potassium intake on mitigating hypertension risk has been demonstrated in clinical and observational research. The role that modified sodium or potassium intake plays in influencing the renin-angiotensin system, arterial stiffness, and endothelial dysfunction remains of interest in current research. Up to the present date, no known systematic review has examined whether the sodium-to-potassium ratio or either sodium or potassium alone is more strongly associated with blood pressure and related factors, including the renin-angiotensin system, arterial stiffness, the augmentation index, and endothelial dysfunction, in humans. This article presents a systematic review and synthesis of the randomized controlled trials and observational research related to this issue. The main findings show that, among the randomized controlled trials reviewed, the sodium-to-potassium ratio appears to be more strongly associated with blood pressure outcomes than either sodium or potassium alone in hypertensive adult populations. Recent data from the observational studies reviewed provide additional support for the sodium-to-potassium ratio as a superior metric to either sodium or potassium alone in the evaluation of blood pressure outcomes and incident hypertension. It remains unclear whether this is true in normotensive populations and in children and for related outcomes including the renin-angiotensin system, arterial stiffness, the augmentation index, and endothelial dysfunction. Future study in these populations is warranted. PMID:25398734

Patient- and physician-related risk factors for hyperkalaemia in potassium-increasing drug-drug interactions.

PubMed

Eschmann, Emmanuel; Beeler, Patrick E; Kaplan, Vladimir; Schneemann, Markus; Zünd, Gregor; Blaser, Jürg

2014-02-01

Hyperkalaemia due to potassium-increasing drug-drug interactions (DDIs) is a clinically important adverse drug event. The purpose of this study was to identify patient- and physician-related risk factors for the development of hyperkalaemia. The risk for adult patients hospitalised in the University Hospital Zurich between 1 December 2009 and 31 December 2011 of developing hyperkalaemia was correlated with patient characteristics, number, type and duration of potassium-increasing DDIs and frequency of serum potassium monitoring. The 76,467 patients included in this study were prescribed 8,413 potentially severe potassium-increasing DDIs. Patient-related characteristics associated with the development of hyperkalaemia were pulmonary allograft [relative risk (RR) 5.1; p < 0.0001), impaired renal function (RR 2.7; p < 0.0001), diabetes mellitus (RR 1.6; p = 0.002) and female gender (RR 1.5; p = 0.007). Risk factors associated with medication were number of concurrently administered potassium-increasing drugs (RR 3.3 per additional drug; p < 0.0001) and longer duration of the DDI (RR 4.9 for duration ≥6 days; p < 0.0001). Physician-related factors associated with the development of hyperkalaemia were undetermined or elevated serum potassium level before treatment initiation (RR 2.2; p < 0.001) and infrequent monitoring of serum potassium during a DDI (interval >48 h: RR 1.6; p < 0.01). Strategies for reducing the risk of hyperkalaemia during potassium-increasing DDIs should consider both patient- and physician-related risk factors.

Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes.

PubMed

Bekar, Lane K; Loewen, Matthew E; Cao, Kun; Sun, Xianfeng; Leis, Jerome; Wang, Rui; Forsyth, George W; Walz, Wolfgang

2005-03-01

Voltage-gated potassium channels are well established as critical for setting action potential frequency, membrane potential, and neurotransmitter release in neurons. However, their role in the "nonexcitable" glial cell type is yet to be fully understood. We used whole cell current kinetics, pharmacology, immunocytochemistry, and RT-PCR to characterize A-type current in hippocampal astrocyte cultures to better understand its function. Pharmacological analysis suggests that approximately 70, 10, and <5% of total A current is associated with Kv4, Kv3, and Kv1 channels, respectively. In addition, pharmacology and kinetics provide evidence for a significant contribution of KChIP accessory proteins to astrocytic A-channel composition. Localization of the Shaw Kv3.4 channel to astrocytic processes and the Shal Kv4.3 channel to soma suggest that these channels serve a specific function. Given this complex A-type channel expression pattern, we assessed the role of A currents in membrane voltage oscillations in response to current injections. Although TEA-sensitive delayed-rectifying currents are involved in the extent of repolarization, 4-AP-sensitive A currents serve to increase the rate. As in neurons, this effect may enable astrocytes to respond rapidly to high-frequency synaptic events. Our results indicate that hippocampal astrocytes in vitro express multiple A-type Kv channel alpha-subunits with accessory, possibly Ca(2+)-sensitive, cytoplasmic subunits that appear to be specifically localized to subcellular membrane compartments. Function of these channels remains to be determined in a physiological setting. However, this study suggests that they enable astrocytes to respond rapidly with membrane voltage oscillations to high-frequency incoming signals, possibly synchronizing astrocyte function to neuronal activity.

[Effects of nitrogen application rates and straw returning on nutrient balance and grain yield of late sowing wheat in rice-wheat rotation].

PubMed

Zhang, Shan; Shi, Zu-liang; Yang, Si-jun; Gu, Ke-jun; Dai, Ting-bo; Wang, Fei; Li, Xiang; Sun, Ren-hua

2015-09-01

Field experiments were conducted to study the effects of nitrogen application rates and straw returning on grain yield, nutrient accumulation, nutrient release from straw and nutrient balance in late sowing wheat. The results showed that straw returning together with appropriate application of nitrogen fertilizer improved the grain yield. Dry matter, nitrogen, phosphorus and potassium accumulation increased significantly as the nitrogen application rate increased. At the same nitrogen application rate (270 kg N · hm(-2)), the dry matter, phosphorus and potassium accumulation of the treatment with straw returning were higher than that without straw returning, but the nitrogen accumulation was lower. Higher-rate nitrogen application promoted straw decomposition and nutrient release, and decreased the proportion of the nutrient released from straw after jointing. The dry matter, phosphorus and potassium release from straw showed a reverse 'N' type change with the wheat growing, while nitrogen release showed a 'V' type change. The nutrient surplus increased significantly with the nitrogen application rate. At the nitrogen application rate for the highest grain yield, nitrogen and potassium were surplus significantly, and phosphorus input could keep balance. It could be concluded that as to late sowing wheat with straw returning, applying nitrogen at 257 kg · hm(-2) and reducing potassium fertilizer application could improve grain yield and reduce nutrients loss.

Determination of mixing state and sources of wintertime organic aerosol in Paris using single particle mass spectrometry

NASA Astrophysics Data System (ADS)

Healy, R. M.; Sciare, J.; Poulain, L.; Wiedensohler, A.; Jeong, C.; McGuire, M.; Evans, G. J.; McGillicuddy, E.; O'Connor, I. P.; Sodeau, J. R.; Wenger, J.

2012-12-01

The size-resolved chemical composition of single particles at an urban background site in Paris, France, was determined using an Aerosol Time-Of-Flight Mass Spectrometer (ATOFMS) as part of the MEGAPOLI winter campaign in January/February 2010. A variety of mixing states were identified for organic aerosol by mass spectral clustering and apportioned to both fossil fuel and biomass burning sources. The ATOFMS data were scaled in order to produce mass concentration estimates for each organic aerosol particle type identified. Potassium-containing organic aerosol internally mixed with nitrate, associated with local wood burning, was observed to dominate during periods characterised by marine air masses. Sulfate-rich potassium-containing organic aerosol, associated with transboundary transport of biomass burning emissions, dominated during periods influenced by continental air masses. The scaled total mass concentration for potassium-containing particles was well correlated (R2 = 0.79) with concurrent measurements of potassium mass concentration measured with a Particle-Into-Liquid-Sampler (PILS). Another organic particle type, also containing potassium but rich in trimethylamine and sulfate, was detected exclusively during continental air mass events. These particles are postulated to have accumulated gas phase trimethylamine through heterogeneous reaction before arriving at the sampling site. Potential source regions for transboundary organic aerosols have been investigated using the potential source contribution function (PSCF). Comparison with aerosol mass spectrometer (AMS) measurements will also be discussed.

76 FR 28419 - Persulfates From the People's Republic of China: Final Results of the 2009-2010 Antidumping Duty...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-17

... ammonium, potassium, and sodium persulfates. The chemical formula for these persulfates are, respectively, (NH 4 ) 2 S 2 O 8 , K 2 S 2 O 8 , and Na 2 S 2 O 8 . Potassium persulfates are currently classifiable...

Bartter's syndrome with type 2 diabetes mellitus.

PubMed

See, Ting-Ting; Lee, Siu-Pak

2009-02-01

We report a rare case of Bartter's syndrome in a 35-year-old woman with type 2 diabetes mellitus. The patient presented with leg weakness, fatigue, polyuria and polydipsia. Hypokalemia, metabolic alkalosis, and high renin and aldosterone concentrations were present, but the patient was normotensive. Gitelman's syndrome was excluded because of the presence of hypercalciuria, secondary hyperparathyroidism and bilateral nephrocalcinosis. The patients condition improved upon administration of a prostaglandin synthetase inhibitor (acemetacin), oral potassium chloride and potassium-sparing diuretics. Five months later, the patient discontinued acemetacin because of epigastric discomfort; at the same time, severe hypokalemia and hyperglycemia developed. Glucagon stimulation and water deprivation tests were performed. Type 2 diabetes mellitus with nephrogenic diabetes insipidus was diagnosed. To avoid further gastrointestinal complications, the patient was treated with celecoxib, a selective cyclooxygenase 2 inhibitor. This case serves as a reminder that Bartter's syndrome is associated with various metabolic derangements including nephrogenic diabetes insipidus, nephrocalcinosis and diabetes mellitus. When treating Bartter's syndrome, it is also prudent to remember that the long-term use of nonsteroidal anti-inflammatory drugs and potassium-sparing diuretics may result in serious adverse reactions.

LGI1 tunes intrinsic excitability by regulating the density of axonal Kv1 channels.

PubMed

Seagar, Michael; Russier, Michael; Caillard, Olivier; Maulet, Yves; Fronzaroli-Molinieres, Laure; De San Feliciano, Marina; Boumedine-Guignon, Norah; Rodriguez, Léa; Zbili, Mickael; Usseglio, Fabrice; Formisano-Tréziny, Christine; Youssouf, Fahamoe; Sangiardi, Marion; Boillot, Morgane; Baulac, Stéphanie; Benitez, María José; Garrido, Juan-José; Debanne, Dominique; El Far, Oussama

2017-07-18

Autosomal dominant epilepsy with auditory features results from mutations in leucine-rich glioma-inactivated 1 (LGI1), a soluble glycoprotein secreted by neurons. Animal models of LGI1 depletion display spontaneous seizures, however, the function of LGI1 and the mechanisms by which deficiency leads to epilepsy are unknown. We investigated the effects of pure recombinant LGI1 and genetic depletion on intrinsic excitability, in the absence of synaptic input, in hippocampal CA3 neurons, a classical focus for epileptogenesis. Our data indicate that LGI1 is expressed at the axonal initial segment and regulates action potential firing by setting the density of the axonal Kv1.1 channels that underlie dendrotoxin-sensitive D-type potassium current. LGI1 deficiency incurs a >50% down-regulation of the expression of Kv1.1 and Kv1.2 via a posttranscriptional mechanism, resulting in a reduction in the capacity of axonal D-type current to limit glutamate release, thus contributing to epileptogenesis.

Inhibitory effects of pimozide on cloned and native voltage-gated potassium channels.

PubMed

Zhang, Zhi-Hao; Lee, Yan T; Rhodes, Kenneth; Wang, Kewei; Argentieri, Thomas M; Wang, Qiang

2003-07-04

The primary goal of this study was to use the cloned neuronal Kv channels to test if pimozide (PMZD), an antipsychotic drug, modulates the activity of Kv channels. In CHO cells, PMZD blocked Kv2.1, a major neuronal delayed rectifier, in a manner that depends upon time and concentration. The estimated IC50 was 4.2 microM at +50 mV. Tail current analysis shows that PMZD reduced the amplitude of the currents, with no effect on the steady-state activation curve (V(1/2) from 14.1 to 11.1 mV) or the slope (16.7 vs. 14.0 mV). From -120 to -20 mV, PMZD did not impact the deactivation kinetics of Kv2.1. PMZD also blocked Kv1.1, another neuronal delayed rectifier, with 16.1 microM of IC50. When Kv1.1 was co-expressed with Kvbeta1, approximately 50% of the Kv1.1 were converted into an inactivating A-type current and the Kv1.1/Kvbeta1 A-type currents were insensitive to PMZD. PMZD (10 microM) had minimal effect on Kv1.4, and had no effect on the M-current candidates, KCNQ2 and KCNQ3 when co-expressed in Xenopus oocytes. In hippocampal neurons, PMZD inhibited the delayed rectifiers by approximately 60%, and A-type currents were insensitive to PMZD. The results suggest that PMZD inhibits certain neuronal Kv channels in heterologous expression systems and in hippocampal neurons. PMZD was less effective on A-type currents, presumably because its ability to block requires a prolonged opening of the K channels. It is thus conceivable that the time-dependent and/or subunit-specific inhibition of Kv channels may increase the release of neurotransmitters such as serotonin and glutamate.

Study on Self-start up of Polymer Electrolyte Fuel Cell Stack at Subzero Temperature

NASA Astrophysics Data System (ADS)

Shirato, Hiroyasu; Hoshina, Hideo; Yamakoshi, Yukiyasu; Tomita, Kazuhiko; Oka, Yoshiaki

This paper aims to boot up polymer electrolyte fuel cells at subzero temperature without energy from outside and compass the conditions. Visualization tests of water drainage and voltage-current density characteristics provided the selection of a serpentine type as a channel of a fuel cell separator for cold region. The successful start-up of the cell at subzero temperature requires suitable current densities corresponding to the ambient temperature since the lower the temperature is, the lower the cell voltage soon after the start-up is. Suitable amount of exhausted energy is also necessary for the successful self start-up. Humidification using potassium acetate 30 mass% solution provides increased impedance of the cell and inhibits the water freezing owing to its dispersal to the electrode compared to no humidification. A stack laminated 25 sheets of the serpentine type separators enables stabilized power generation at normal temperature. The stack is also bootable with no energy from outside at 263K.

Laser-induced breakdown spectroscopy (LIBS) for rapid analysis of ash, potassium and magnesium in gluten free flours.

PubMed

Markiewicz-Keszycka, Maria; Casado-Gavalda, Maria P; Cama-Moncunill, Xavier; Cama-Moncunill, Raquel; Dixit, Yash; Cullen, Patrick J; Sullivan, Carl

2018-04-01

Gluten free (GF) diets are prone to mineral deficiency, thus effective monitoring of the elemental composition of GF products is important to ensure a balanced micronutrient diet. The objective of this study was to test the potential of laser-induced breakdown spectroscopy (LIBS) analysis combined with chemometrics for at-line monitoring of ash, potassium and magnesium content of GF flours: tapioca, potato, maize, buckwheat, brown rice and a GF flour mixture. Concentrations of ash, potassium and magnesium were determined with reference methods and LIBS. PCA analysis was performed and presented the potential for discrimination of the six GF flours. For the quantification analysis PLSR models were developed; R 2 cal were 0.99 for magnesium and potassium and 0.97 for ash. The study revealed that LIBS combined with chemometrics is a convenient method to quantify concentrations of ash, potassium and magnesium and present the potential to classify different types of flours. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of female steroid hormones on A-type K+ currents in murine colon.

PubMed

Beckett, Elizabeth A H; McCloskey, Conor; O'Kane, Neil; Sanders, Kenton M; Koh, Sang Don

2006-06-01

Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K(+) channels serve to set the excitability of colonic muscles. We investigated regulation of Kv 4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv 4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause.

BK Channels Are Required for Multisensory Plasticity in the Oculomotor System.

PubMed

Nelson, Alexandra B; Faulstich, Michael; Moghadam, Setareh; Onori, Kimberly; Meredith, Andrea; du Lac, Sascha

2017-01-04

Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium-activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually evoked eye movements rapidly restore oculomotor function in wild-type mice but are profoundly impaired in BK channel-null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits. Copyright © 2017 Elsevier Inc. All rights reserved.

A heteromeric potassium channel involved in the modulation of the plasma membrane potential is essential for the survival of African trypanosomes.

PubMed

Steinmann, Michael E; González-Salgado, Amaia; Bütikofer, Peter; Mäser, Pascal; Sigel, Erwin

2015-08-01

Discovery of novel drug targets may lead to improved treatment of trypanosomiasis. We characterize here 2 gene products of Trypanosoma brucei that are essential for the growth of bloodstream form (BSF) parasites, as shown by RNA interference (RNAi)-mediated down-regulation of the individual mRNAs. The primary sequences of the 2 proteins--protein encoded by gene Tb927.1.4450 (TbK1) and protein encoded by gene Tb927.9.4820 (TbK2)--indicate that both belong to the family of putative, Ca(2+)-activated potassium channels. The proteins were expressed in Xenopus laevis oocytes and their functions investigated by use of electrophysiological techniques. Only combined expression of TbK1 and TbK2 results in the formation of sizeable currents, indicating that these proteins probably assemble into a heteromeric ion channel. The current mediated by this channel shows little time and voltage dependence and displays a permeability ratio of K(+)/Na(+) of >20. The known potassium channel blocker barium inhibits this channel with a half-maximal inhibitory concentration (IC50) of 98 ± 15 μM. The membrane potential of trypanosomes was measured with a fluorescent dye. Individual RNAi-mediated down-regulation of TbK1 or TbK2 eliminates a potassium conductance in the plasma membrane of BSF. Thus, this heteromeric potassium channel is involved in the modulation of the plasma membrane potential and represents a novel drug target in T. brucei. © FASEB.

Functional significance of M-type potassium channels in nociceptive cutaneous sensory endings

PubMed Central

Passmore, Gayle M.; Reilly, Joanne M.; Thakur, Matthew; Keasberry, Vanessa N.; Marsh, Stephen J.; Dickenson, Anthony H.; Brown, David A.

2012-01-01

M-channels carry slowly activating potassium currents that regulate excitability in a variety of central and peripheral neurons. Functional M-channels and their Kv7 channel correlates are expressed throughout the somatosensory nervous system where they may play an important role in controlling sensory nerve activity. Here we show that Kv7.2 immunoreactivity is expressed in the peripheral terminals of nociceptive primary afferents. Electrophysiological recordings from single afferents in vitro showed that block of M-channels by 3 μM XE991 sensitized Aδ- but not C-fibers to noxious heat stimulation and induced spontaneous, ongoing activity at 32°C in many Aδ-fibers. These observations were extended in vivo: intraplantar injection of XE991 selectively enhanced the response of deep dorsal horn (DH) neurons to peripheral mid-range mechanical and higher range thermal stimuli, consistent with a selective effect on Aδ-fiber peripheral terminals. These results demonstrate an important physiological role of M-channels in controlling nociceptive Aδ-fiber responses and provide a rationale for the nocifensive behaviors that arise following intraplantar injection of the M-channel blocker XE991. PMID:22593734

Interaction of the scorpion toxin discrepin with Kv4.3 channels and A-type K(+) channels in cerebellum granular cells.

PubMed

Picco, Cristiana; Corzo, Gerardo; Possani, Lourival D; Prestipino, Gianfranco

2014-09-01

The peptide discrepin from the α-KTx15 subfamily of scorpion toxins preferentially affects transient A-type potassium currents, which regulate many aspects of neuronal function in the central nervous system. However, the specific Kv channel targeted by discrepin and the molecular mechanism of interaction are still unknown. Different variant peptides of discrepin were chemically synthesized and their effects were studied using patch clamp technique on rat cerebellum granular cells (CGC) and HEK cells transiently expressing Kv4.3 channels. Functional analysis indicated that nanomolar concentrations of native discrepin blocked Kv4.3 expressed channels, as previously observed in CGC. Similarly, the apparent affinities of all mutated peptides for Kv4.3 expressed channels were analogous to those found in CGC. In particular, in the double variant [V6K, D20K] the apparent affinity increased about 10-fold, whereas in variants carrying a deletion (ΔK13) or substitution (K13A) at position K13, the blockage was removed and the apparent affinity decreased more than 20-fold. These results indicate that Kv4.3 is likely the target of discrepin and highlight the importance of the basic residue K13, located in the α-helix of the toxin, for current blockage. We report the first example of a Kv4 subfamily potassium channel blocked by discrepin and identify the amino acid residues responsible for the blockage. The availability of discrepin variant peptides stimulates further research on the functions and pharmacology of neuronal Kv4 channels and on their possible roles in neurodegenerative disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Reduction of potassium content of green bean pods and chard by culinary processing. Tools for chronic kidney disease.

PubMed

Martínez-Pineda, Montserrat; Yagüe-Ruiz, Cristina; Caverni-Muñoz, Alberto; Vercet-Tormo, Antonio

2016-01-01

In order to prevent a possible hyperkalemia, chronic renal patients, especially in advanced stages, must follow a low potassium diet. So dietary guidelines for chronic kidney disease recommend limiting the consumption of many vegetables, as well as to apply laborious culinary techniques to maximize the reduction of potassium. The aim of this work is to analyze potassium content from several vegetable, fresh products, frozen and preserved, as well as check and compare the effectiveness in potassium reduction of different culinary processes, some of them recommended in dietary guidelines such as soaking or double cooking. Sample potassium content was analyzed by triplicate using flamephotometry. The results showed significant reductions in potassium content in all culinary processes studied. The degree of loss varied depending on the type of vegetable and processing applied. Frozen products achieved greater reductions than the fresh ones, obtaining in some cases losses greater than 90%. In addition, it was observed how in many cases the single application of a normal cooking reached potassium reductions to acceptable levels for its inclusion in renal patient diet. The results shown in this study are very positive because they provide tools for professionals who deal with this kind of patients. They allow them to adapt more easily to the needs and preferences of their patients and increase dietary variety. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Serum and Dietary Potassium and Risk of Incident Type 2 Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Chatterjee, Ranee; Yeh, Hsin-Chieh; Shafi, Tariq; Selvin, Elizabeth; Anderson, Cheryl; Pankow, James S.; Miller, Edgar; Brancati, Frederick

2012-01-01

Background Serum potassium levels affect insulin secretion by pancreatic beta-cells, and hypokalemia associated with diuretic use has been associated with dysglycemia. We hypothesized that adults with lower serum potassium levels and lower dietary potassium intake are at higher risk for incident diabetes, independent of diuretic use. Methods We analyzed data from 12,209 participants from the Atherosclerosis Risk in Communities (ARIC) Study, an on-going prospective cohort study beginning in 1986, with 9 years of in-person follow-up and 17 years of telephone follow-up. Using multivariate Cox proportional hazard models, we estimated the relative hazard (RH) of incident diabetes associated with baseline serum potassium levels. Results During 9 years of in-person follow-up, 1475 participants developed incident diabetes. In multivariate analyses, we found an inverse association between serum potassium and risk of incident diabetes. Compared to those with a high-normal serum potassium (5.0-5.5 mEq/l), adults with serum potassium levels of < 4.0, 4.0-<4.5, and 4.5-<5.0, (mEq/L) had adjusted relative hazards (RH) (95% CI) of incident diabetes of 1.64 (1.29-2.08), 1.64 (1.34-2.01), and 1.39 (1.14-1.71) respectively. An increased risk persisted during an additional 8 years of telephone follow-up based on self-report with RHs of 1.2-1.3 for those with a serum potassium less than 5.0 mEq/L. Dietary potassium intake was significantly associated with risk of incident diabetes in unadjusted models but not in multivariate models. Conclusions Serum potassium is an independent predictor of incident diabetes in this cohort. Further study is needed to determine if modification of serum potassium could reduce the subsequent risk of diabetes. PMID:20975023

Serum and dietary potassium and risk of incident type 2 diabetes mellitus: The Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Chatterjee, Ranee; Yeh, Hsin-Chieh; Shafi, Tariq; Selvin, Elizabeth; Anderson, Cheryl; Pankow, James S; Miller, Edgar; Brancati, Frederick

2010-10-25

Serum potassium levels affect insulin secretion by pancreatic β-cells, and hypokalemia associated with diuretic use has been associated with dysglycemia. We hypothesized that adults with lower serum potassium levels and lower dietary potassium intake are at higher risk for incident diabetes mellitus (DM), independent of diuretic use. We analyzed data from 12 209 participants from the Atherosclerosis Risk in Communities (ARIC) Study, an ongoing prospective cohort study, beginning in 1986, with 9 years of in-person follow-up and 17 years of telephone follow-up. Using multivariate Cox proportional hazard models, we estimated the hazard ratio (HR) of incident DM associated with baseline serum potassium levels. During 9 years of in-person follow-up, 1475 participants developed incident DM. In multivariate analyses, we found an inverse association between serum potassium and risk of incident DM. Compared with those with a high-normal serum potassium level (5.0-5.5 mEq/L), adults with serum potassium levels lower than 4.0 mEq/L, 4.0 to lower than 4.5 mEq/L, and 4.5 to lower than 5.0 mEq/L had an adjusted HR (95% confidence interval [CI]) of incident DM of 1.64 (95% CI, 1.29-2.08), 1.64 (95% CI, 1.34-2.01), and 1.39 (95% CI, 1.14-1.71), respectively. An increased risk persisted during an additional 8 years of telephone follow-up based on self-report with HRs of 1.2 to 1.3 for those with a serum potassium level lower than 5.0 mEq/L. Dietary potassium intake was significantly associated with risk of incident DM in unadjusted models but not in multivariate models. Serum potassium level is an independent predictor of incident DM in this cohort. Further study is needed to determine if modification of serum potassium could reduce the subsequent risk of DM.

Butanolysis: Comparison of potassium hydroxide and potassium tert-butoxide as catalyst for biodiesel preparing from rapeseed oil.

PubMed

Musil, Martin; Skopal, Frantisek; Hájek, Martin; Vavra, Ales

2018-07-15

Biodiesel is a mixture of esters of fatty acids (most often palmitic, stearic and oleic) and lower alcohols (in our work butanol) produced by transesterification. It is a renewable source of energy, prepared from triacylglycerides, which are contained in vegetable oils and animal fats. This work focuses on alkaline catalyzed transesterification of rapeseed oil with butanol and comparison of two catalysts (potassium hydroxide and potassium tert-butoxide). In industry is usually transesterification of rapeseed oil carried out like reaction catalyzed by potassium hydroxide. Potassium hydroxide have high content of K 2 CO 3 , KHCO 3 and water. Moreover water is formed by neutralization of potassium hydroxide with free fatty acids contained in oil. In cause of tert-butoxide catalyzed reaction, it is not possible because tert-butoxide have not a OH - aniont, which is needed for water forming. The influence of various conditions (addition of water, temperature of separation, intensity of stirring and type of catalyst) on butanolysis process was studied for both catalysts. For both catalysts dependence of conversions on time were plotted. When tert-butoxide was used, satisfactory phase separation was not achieved. The only way was separation of hot crude reaction mixture without adding water. Ester formed by this method had high content of free glycerol and soaps, but reached higher conversion. The best results were obtained with KOH and subsequent separation of cold crude reaction mixture with the addition of water and slow stirring. The difference between reactions catalyzed by potassium hydroxide and potassium tert-butoxide was described. Copyright © 2018 Elsevier Ltd. All rights reserved.

Managing Hyperkalemia: Stepping Into a New Frontier.

PubMed

Pham, Antony Q; Sexton, Jessica; Wimer, Dexter; Rana, Isha; Nguyen, Timothy

2017-10-01

Maintaining potassium balance in the body is essential for cellular function. Even a slight increase in normal serum potassium levels (3.5-5.0 mEq/L) can interfere with metabolism, electrical action potentials, and cellular processes. Hyperkalemia is commonly seen in patients with chronic kidney disease (CKD) and in patients on renin-angiotensin-aldosterone system (RAAS) inhibitors. Sodium polystyrene sulfonate (SPS), diuretics, and hemodialysis are currently available methods for removing potassium from the body; however, these options have their limitations. Patiromer (Veltassa) and sodium zirconium cyclosilicate are 2 new therapeutic options that can potentially lead a new frontier in the management of hyperkalemia. This article will review these novel treatments.

Effect of potassium fertilizer application on the yield and quality of current sugarcane varieties in Louisiana

USDA-ARS?s Scientific Manuscript database

For many sugarcane producers in Louisiana the only fertilizer that is routinely applied to their crop is nitrogen that is side-dressed in the spring. This is due, primarily to the high cost of potassium and phosphorus fertilizers. Recent cooperative research conducted between the USDA/ARS Sugarcane ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Ching-Shin; Pedersen, Bjørn Panyella; Stokes, David L.

Cellular potassium import systems play a fundamental role in osmoregulation, pH homeostasis and membrane potential in all domains of life. In bacteria, the kdp operon encodes a four-subunit potassium pump that maintains intracellular homeostasis, cell shape and turgor under conditions in which potassium is limiting1. This membrane complex, called KdpFABC, has one channel-like subunit (KdpA) belonging to the superfamily of potassium transporters and another pump-like subunit (KdpB) belonging to the superfamily of P-type ATPases. Although there is considerable structural and functional information about members of both superfamilies, the mechanism by which uphill potassium transport through KdpA is coupled with ATPmore » hydrolysis by KdpB remains poorly understood. Here we report the 2.9 Å X-ray structure of the complete Escherichia coli KdpFABC complex with a potassium ion within the selectivity filter of KdpA and a water molecule at a canonical cation site in the transmembrane domain of KdpB. The structure also reveals two structural elements that appear to mediate the coupling between these two subunits. Specifically, a protein-embedded tunnel runs between these potassium and water sites and a helix controlling the cytoplasmic gate of KdpA is linked to the phosphorylation domain of KdpB. On the basis of these observations, we propose a mechanism that repurposes protein channel architecture for active transport across biomembranes.« less

The effect of use of dates on serum potassium in nondiabetic hemodialysis patients.

PubMed

Siddiqi, Nauman; El Shahat, Osama; Bokhari, Ebtisam; Roujouleh, Haytham; Hamid, M Hisham; Sheikh, Iftikhar; El-Sayed, Hassan; Saleh, Ayman; Seddik, Ayman

2009-11-01

Hyperkalemia is common in patients with ESRD and may contribute to mortality. Dates have been reported to be high in potassium content. One of the concerns on hemodialysis (HD) is convincing patients to give up ingestion of dates as a part of their diet. To determine the effect of dates on serum potassium on patients, we studied 9 (M: F, 6:3, mean age 47.6) non diabetic patients on chronic hemodialysis, without evidence of hyperkalemia on monthly labs. Nearly all the patients had been on dialysis for an average of four years. The average monthly potassium was 4.6 mmol/L. The patients ingested 100 gm of dates (Rothana and Sukari) on two separate dialysis sessions. Serum potassium was measured at two and four hours post ingestion along with ECG monitoring. The patients underwent their regular dialysis as scheduled. The patients acted as their own controls and underwent the same protocol with 20meq of KCl on a separate session. The potassium levels did not change significantly over the four hours with either variety of dates or with potassium solution. Combining the two types of dates resulted in a trend towards higher potassium levels than with KCl, but it did not reach statistical significance. We conclude that in selected HD patients without hyperkalemia, ingestion of a few dates does not cause significant hyperkalemia and could be allowed on days of dialysis prior to their dialysis sessions.

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

PubMed

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.

Ionic mechanism of a two-component cholinergic inhibition in Aplysia neurones

PubMed Central

Kehoe, Jacsue

1972-01-01

1. A two-component inhibition, consisting of a rapid and slow i.p.s.p., has been observed in the medial cells of the pleural ganglion of Aplysia. Each i.p.s.p. has been shown to be mediated by a distinct cholinergic receptor. The ionic mechanisms of the two components of the inhibitory response (whether elicited synaptically or by ACh injection) are analysed in this paper. 2. The inversion potential (typically -60 mV) of the rapid i.p.s.p. and of the rapid response to ACh injection is selectively altered by an intracellular injection of chloride or by partial substitution of the external chloride by impermeant anions. The shift caused by this last procedure is similar to that predicted for the chloride equilibrium potential (ECl) by the Nernst equation. 3. The slow i.p.s.p. and the slow response to ACh injection (both of which invert around -80 mV) are insensitive to changes in either internal or external chloride concentrations; on the contrary, with alterations of the concentration of potassium in the external medium, the inversion potential of the slow responses is altered in a way similar to that expected for the potassium equilibrium potential (EK). 4. It is concluded that the rapid i.p.s.p. and the corresponding ACh potential are due to a change in chloride permeability of the post-synaptic membrane, whereas the slow responses are due to a selective change in potassium permeability. 5. Additional data suggest that the fast, `chloride' channel is impermeable to sulphate and methylsulphate, but slightly permeable to propionate and isethionate. The slow, `potassium' channel is impermeable to caesium ions, whereas its permeability to rubidium ions is half that to potassium. 6. The potassium permeability of both the non-synaptic and synaptic membrane is markedly reduced by an intracellular injection of either tetraethylammonium (TEA) or caesium. These ions not only block the cholinergic potassium currents (whether inward or outward) but likewise block the potassium currents activated in the same cells by an iontophoretic injection of dopamine. 7. The potassium dependent synaptic potentials are also selectively affected by manipulations known to block the electrogenic sodium pump. In the presence of ouabain or in sea water in which sodium has been replaced by lithium, there is an apparent reduction of these potentials which was shown to be simply a reflexion of the movement of EK towards a less polarized level. This shift in inversion potential was not seen for the potassium dependent response to ACh iontophoretic injection. These results are interpreted in terms of accumulation of potassium ions assumed to occur in the extracellular spaces of the neuropile, but not in the thoroughly dissected somatic region. 8. Cooling was shown to eliminate, selectively, the synaptic and ACh potential changes caused by an increase in potassium permeability. PMID:4679686

Recent developments in nickel electrode analysis

NASA Technical Reports Server (NTRS)

Whiteley, Richard V.; Daman, M. E.; Kaiser, E. Q.

1991-01-01

Three aspects of nickel electrode analysis for Nickel-Hydrogen and Nickel-Cadmium battery cell applications are addressed: (1) the determination of active material; (2) charged state nickel (as NiOOH + CoOOH); and (3) potassium ion content in the electrode. Four deloading procedures are compared for completeness of active material removal, and deloading conditions for efficient active material analyses are established. Two methods for charged state nickel analysis are compared: the current NASA procedure and a new procedure based on the oxidation of sodium oxalate by the charged material. Finally, a method for determining potassium content in an electrode sample by flame photometry is presented along with analytical results illustrating differences in potassium levels from vendor to vendor and the effects of stress testing on potassium content in the electrode. The relevance of these analytical procedures to electrode performance is reviewed.

Resonance Properties of Class I and Class II Neurons Differentially Modulated by Channel Noise

NASA Astrophysics Data System (ADS)

Wang, Lei

2018-01-01

Resonance properties of two different neuron types (Class I and Class II) induced by channel noise are investigated in this study. It is found that for Class I neuron, spiking activity is enhanced when certain noise intensity is presented, especially under weak current stimuli -- a typical phenomenon of stochastic resonance (SR); while for Class II neuron, in addition to perform the SR, certain noise intensity would inhibit neuronal activity under some current stimuli -- a typical phenomenon of inverse stochastic resonance (ISR). Moreover, we show that only sodium channel noise or potassium channel noise variation can achieve the similar phenomena. Consequently, the model results suggest that channel noise may exert differential roles in modulating the resonance properties of Class I and Class II neurons.

A kinetic study on the catalysis of KCl, K2SO4, and K2CO3 during oxy-biomass combustion.

PubMed

Deng, Shuanghui; Wang, Xuebin; Zhang, Jiaye; Liu, Zihan; Mikulčić, Hrvoje; Vujanović, Milan; Tan, Houzhang; Duić, Neven

2018-07-15

Biomass combustion under the oxy-fuel conditions (Oxy-biomass combustion) is one of the approaches achieving negative CO 2 emissions. KCl, K 2 CO 3 and K 2 SO 4 , as the major potassium species in biomass ash, can catalytically affect biomass combustion. In this paper, the catalysis of the representative potassium salts on oxy-biomass combustion was studied using a thermogravimetric analyzer (TGA). Effects of potassium salt types (KCl, K 2 CO 3 and K 2 SO 4 ), loading concentrations (0, 1, 3, 5, 8 wt%), replacing N 2 by CO 2 , and O 2 concentrations (5, 20, 30 vol%) on the catalysis degree were discussed. The comparison between TG-DTG curves of biomass combustion before and after water washing in both the 20%O 2 /80%N 2 and 20%O 2 /80%CO 2 atmospheres indicates that the water-soluble minerals in biomass play a role in promoting the devolatilization and accelerating the char-oxidation; and the replacement of N 2 by CO 2 inhibits the devolatilization and char-oxidation processes during oxy-biomass combustion. In the devolatilization stage, the catalysis degree of potassium monotonously increases with the increase of potassium salt loaded concentration. The catalysis degree order of the studied potassium salts is K 2 CO 3  > KCl > K 2 SO 4 . In the char-oxidation stage, with the increase of loading concentration the three kinds of potassium salts present inconsistent change tendencies of the catalysis degree. In the studied loading concentrations from 0 to 8 wt%, there is an optimal loading concentration for KCl and K 2 CO 3 , at 3 and 5 wt%, respectively; while for K 2 SO 4 , the catalysis degree on char-oxidation monotonically increases with the loading potassium concentration. For most studied conditions, regardless of the potassium salt types or the loading concentrations or the combustion stages, the catalysis degree in the O 2 /CO 2 atmosphere is stronger than that in the O 2 /N 2 atmosphere. The catalysis degree is also affected by the O 2 concentrations, and the lowest catalysis degree is generally around 20 vol% O 2 concentration. The kinetic parameters under the different studied conditions are finally obtained. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

ERIC Educational Resources Information Center

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…

Drug utilization review of potassium chloride injection formulations available in a private hospital in kuching, sarawak, malaysia.

PubMed

Melissa, Mohammad Hirman; Azmi, Sarriff

2013-07-01

The concentrated potassium chloride injection is a high-alert medication and replacing it with a pre-mixed formulation can reduce the risks associated with its use. The aim of this study was to determine the clinical characteristics of patients receiving different potassium chloride formulations available at a private institution. The study also assessed the effectiveness and safety of pre-mixed formulations in the correction of hypokalaemia. This was a retrospective observational study consisting of 296 cases using concentrated and pre-mixed potassium chloride injections in 2011 in a private hospital in Kuching, Sarawak, Malaysia. There were 135 (45.6%) cases that received concentrated potassium chloride, and 161 (54.4%) cases that received pre-mixed formulations. The patients' clinical characteristics that were significantly related to the utilization of the different formulations were diagnosis (P < 0.001), potassium serum blood concentration (P < 0.05), and fluid overload risk (P < 0.05). The difference observed for the cases that achieved or maintained normokalaemia was statistically insignificant (P = 0.172). Infusion-related adverse effects were seen more in pre-mixes compared to concentrated formulations (6.8% versus 2.2%, P < 0.05). This study provides insight into the utilization of potassium chloride injections at this specific institution. The results support current recommendations to use pre-mixed formulations whenever possible.

Inward Rectifier Potassium Channels Control Rotor Frequency in Ventricular Fibrillation

PubMed Central

Jalife, José

2009-01-01

Summary Ventricular fibrillation (VF) is the most important cause of sudden cardiac death. While traditionally thought to result from random activation of the ventricles by multiple independent wavelets, recent evidence suggests that VF may be determined by the sustained activation of a relatively small number of reentrant sources. In addition, recent experimental data in various species as well as computer simulations have provided important clues about its ionic and molecular mechanisms, particularly in regards to the role of potassium currents in such mechanisms. The results strongly argue that the inward rectifier current, Ik1, is an important current during functional reentry because it mediates the electrotonic interactions between the unexcited core and its immediate surroundings. In addition, IK1 is a stabilizer of reentry due to its ability to shorten action potential duration and reducing conduction velocity near the center of rotation. Increased I K1 prevents wavefront-wavetail interactions and thus averts rotor destabilization and breakup. Other studies have shown that while the slow component of the delayed rectifier potassium current, IKs, does not significantly modify rotor frequency or stability, it plays a major role in post-repolarization refractoriness and wavebreak formation. Therefore, the interplay between IK1 and the rapid sodium inward current (INa) is a major factor in the control of cardiac excitability and therefore the stability and frequency of reentry while IKs is an important determinant of fibrillatory conduction. PMID:19880073

Volume Measurements of Laser-generated Pits for in Situ Geochronology Using KArLE (Potassium-Argon Laser Experiment)

NASA Technical Reports Server (NTRS)

French, R. A.; Cohen, B. A.; Miller, J. S.

2014-01-01

KArLE (Potassium-­-Argon Laser Experiment) has been developed for in situ planetary geochronology using the K - Ar (potassium-­-argon) isotope system, where material ablated by LIBS (Laser-­-Induced Breakdown Spectroscopy) is used to calculate isotope abundances. We are determining the accuracy and precision of volume measurements of these pits using stereo and laser microscope data to better understand the ablation process for isotope abundance calculations. If a characteristic volume can be determined with sufficient accuracy and precision for specific rock types, KArLE will prove to be a useful instrument for future planetary rover missions.

Enhanced capacity of chemically bonded phosphorus/carbon composite as an anode material for potassium-ion batteries

NASA Astrophysics Data System (ADS)

Wu, Xuan; Zhao, Wei; Wang, Hong; Qi, Xiujun; Xing, Zheng; Zhuang, Quanchao; Ju, Zhicheng

2018-02-01

Potassium-ion batteries are attracting great attention as a promising alternative to lithium-ion batteries due to the abundance and low price of potassium. Herein, the phosphorus/carbon composite, obtained by a simple ball-milling of 20 wt% commercial red phosphorus and 80 wt% graphite, is studied as a novel anode for potassium-ion batteries. Considering the high theoretical specific capacity of phosphorus and formation of stable phosphorus-carbon bond, which can alleviate the volume expansion efficiently, the phosphorus/carbon composite exhibits a high charge capacity of 323.5 mA h g-1 after 50 cycles at a current density of 50 mA g-1 with moderate rate capability and cycling stability. By the X-ray diffraction analysis, the alloying-dealloying mechanism of phosphorus is proposed to form a KP phase. Meanwhile, prepotassiation treatment is conducted to improve the low initial coulomb efficiency.

Solid state electrochemical current source

DOEpatents

Potanin, Alexander Arkadyevich; Vedeneev, Nikolai Ivanovich

2002-04-30

A cathode and a solid state electrochemical cell comprising said cathode, a solid anode and solid fluoride ion conducting electrolyte. The cathode comprises a metal oxide and a compound fluoride containing at least two metals with different valences. Representative compound fluorides include solid solutions of bismuth fluoride and potassium fluoride; and lead fluoride and potassium fluoride. Representative metal oxides include copper oxide, lead oxide, manganese oxide, vanadium oxide and silver oxide.

An ALS-Associated Mutant SOD1 Rapidly Suppresses KCNT1 (Slack) Na+-Activated K+ Channels in Aplysia Neurons.

PubMed

Zhang, Yalan; Ni, Weiming; Horwich, Arthur L; Kaczmarek, Leonard K

2017-02-22

Mutations that alter levels of Slack (KCNT1) Na + -activated K + current produce devastating effects on neuronal development and neuronal function. We now find that Slack currents are rapidly suppressed by oligomers of mutant human Cu/Zn superoxide dismutase 1 (SOD1), which are associated with motor neuron toxicity in an inherited form of amyotrophic lateral sclerosis (ALS). We recorded from bag cell neurons of Aplysia californica , a model system to study neuronal excitability. We found that injection of fluorescent wild-type SOD1 (wt SOD1YFP) or monomeric mutant G85R SOD1YFP had no effect on net ionic currents measured under voltage clamp. In contrast, outward potassium currents were significantly reduced by microinjection of mutant G85R SOD1YFP that had been preincubated at 37°C or of cross-linked dimers of G85R SOD1YFP. Reduction of potassium current was also seen with multimeric G85R SOD1YFP of ∼300 kDa or >300 kDa that had been cross-linked. In current clamp recordings, microinjection of cross-linked 300 kDa increased excitability by depolarizing the resting membrane potential, and decreasing the latency of action potentials triggered by depolarization. The effect of cross-linked 300 kDa on potassium current was reduced by removing Na + from the bath solution, or by knocking down levels of Slack using siRNA. It was also prevented by pharmacological inhibition of ASK1 (apoptosis signal-regulating kinase 1) or of c-Jun N-terminal kinase, but not by an inhibitor of p38 mitogen-activated protein kinase. These results suggest that soluble mutant SOD1 oligomers rapidly trigger a kinase pathway that regulates the activity of Na + -activated K + channels in neurons. SIGNIFICANCE STATEMENT Slack Na + -activated K + channels (KCNT1, K Na 1.1) regulate neuronal excitability but are also linked to cytoplasmic signaling pathways that control neuronal protein translation. Mutations that alter the amplitude of these currents have devastating effects on neuronal development and function. We find that injection of oligomers of mutant superoxide dismutase 1 (SOD1) into the cytoplasm of invertebrate neurons rapidly suppresses these Na + -activated K + currents and that this effect is mediated by a MAP kinase cascade, including ASK1 and c-Jun N-terminal kinase. Because amyotrophic lateral sclerosis is a fatal adult-onset neurodegenerative disease produced by mutations in SOD1 that cause the enzyme to form toxic oligomers, our findings suggest that suppression of Slack channels may be an early step in the progression of the disease. Copyright © 2017 the authors 0270-6474/17/372258-08$15.00/0.

A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability

PubMed Central

Flourakis, Matthieu; Kula-Eversole, Elzbieta; Hutchison, Alan L.; Han, Tae Hee; Aranda, Kimberly; Moose, Devon L.; White, Kevin P.; Dinner, Aaron R.; Lear, Bridget C.; Ren, Dejian; Diekman, Casey O.; Raman, Indira M.; Allada, Ravi

2015-01-01

Summary Circadian clocks regulate membrane excitability in master pacemaker neurons to control daily rhythms of sleep and wake. Here we find that two distinctly timed electrical drives collaborate to impose rhythmicity on Drosophila clock neurons. In the morning, a voltage-independent sodium conductance via the NA/NALCN ion channel depolarizes these neurons. This current is driven by the rhythmic expression of NCA localization factor-1, linking the molecular clock to ion channel function. In the evening, basal potassium currents peak to silence clock neurons. Remarkably, daily antiphase cycles of sodium and potassium currents also drive mouse clock neuron rhythms. Thus, we reveal an evolutionarily ancient strategy for the neural mechanisms that govern daily sleep and wake. PMID:26276633

Use of airborne gamma-ray spectrometry for kaolin exploration

NASA Astrophysics Data System (ADS)

Tourlière, B.; Perrin, J.; Le Berre, P.; Pasquet, J. F.

2003-08-01

Airborne gamma-ray spectrometry was used to define targets with kaolin potential in the Armorican Massif of Brittany, France. This exploration method is based on the principle that kaolinite, an aluminosilicate clay mineral constituting kaolin, is formed by the hydrolysis of potash feldspar with the elimination of potassium. Therefore, potassium contrast between favourable host-rock such as a leucogranite and kaolin occurrence is likely a significant pathfinder. As the relationship between the potassium-40 recorded by an airborne gamma-ray spectrometer and total potassium is constant, such data provide us a direct measurement of the potassium content of the ground flown over. Our study tested this by calculating, for each geological unit, the difference between the measured and average potassium content calculated for a given geological formation. The study was based on (i) a recent (1998) high-definition airborne geophysical survey over the Armorican Massif undertaken on behalf of the French Government, and (ii) new geological compilation maps covering the same region. Depleted zones, where the measured potassium is less than the average potassium content calculated target areas with high potential of containing kaolin, provided that the unit was originally rich in potash feldspar. By applying this method to the entire Armorican Massif, it was possible to identify 150 potassium-depleted zones, including 115 that were subjected to rapid field checks and 36 that contained kaolin (21 new discoveries). This method, which is both safe for the environment and easy to use, is therefore a good tool for rapidly defining targets with kaolin potential at a regional scale. The method may also have possibilities in exploring for other types of deposit characterised by an enrichment or depletion in U, K and/or Th.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bean, Bruce Palmer

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 themore » 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.« less

Use of vitreous carbon as a working electrode in coulometric titration of potassium hydrogen phthalate.

PubMed

Jennings, V J; Dodson, A; Tedds, G

1973-07-01

The use of a vitreous carbon electrode as a cathode in the amperostatic coulometric titration of aqueous potassium hydrogen phthalate solution is described. It is shown that 10 mg of the phthalate can be titrated with a precision better than 0.5%. Current-voltage curves for platinum and vitreous carbon cathodes show that there is an overpotential on the latter relative to the former.

The two-pore domain potassium channel, TWIK-1, has a role in the regulation of heart rate and atrial size.

PubMed

Christensen, Alex Hørby; Chatelain, Franck C; Huttner, Inken G; Olesen, Morten Salling; Soka, Magdalena; Feliciangeli, Sylvain; Horvat, Claire; Santiago, Celine F; Vandenberg, Jamie I; Schmitt, Nicole; Olesen, Søren-Peter; Lesage, Florian; Fatkin, Diane

2016-08-01

The two-pore domain potassium (K(+)) channel TWIK-1 (or K2P1.1) contributes to background K(+) conductance in diverse cell types. TWIK-1, encoded by the KCNK1 gene, is present in the human heart with robust expression in the atria, however its physiological significance is unknown. To evaluate the cardiac effects of TWIK-1 deficiency, we studied zebrafish embryos after knockdown of the two KCNK1 orthologues, kcnk1a and kcnk1b. Knockdown of kcnk1a or kcnk1b individually caused bradycardia and atrial dilation (p<0.001 vs. controls), while ventricular stroke volume was preserved. Combined knockdown of both kcnk1a and kcnk1b resulted in a more severe phenotype, which was partially reversed by co-injection of wild-type human KCNK1 mRNA, but not by a dominant negative variant of human KCNK1 mRNA. To determine whether genetic variants in KCNK1 might cause atrial fibrillation (AF), we sequenced protein-coding regions in two independent cohorts of patients (373 subjects) and identified three non-synonymous variants, p.R171H, p.I198M and p.G236S, that were all located in highly conserved amino acid residues. In transfected mammalian cells, zebrafish and wild-type human TWIK-1 channels had a similar cellular distribution with predominant localization in the endosomal compartment. Two-electrode voltage-clamp experiments using Xenopus oocytes showed that both zebrafish and wild-type human TWIK-1 channels produced K(+) currents that are sensitive to external K(+) concentration as well as acidic pH. There were no effects of the three KCNK1 variants on cellular localization, current amplitude or reversal potential at pH7.4 or pH6. Our data indicate that TWIK-1 has a highly conserved role in cardiac function and is required for normal heart rate and atrial morphology. Despite the functional importance of TWIK-1 in the atrium, genetic variation in KCNK1 is not a common primary cause of human AF. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regulation of Cardiac ATP-sensitive Potassium Channel Surface Expression by Calcium/Calmodulin-dependent Protein Kinase II*

PubMed Central

Sierra, Ana; Zhu, Zhiyong; Sapay, Nicolas; Sharotri, Vikas; Kline, Crystal F.; Luczak, Elizabeth D.; Subbotina, Ekaterina; Sivaprasadarao, Asipu; Snyder, Peter M.; Mohler, Peter J.; Anderson, Mark E.; Vivaudou, Michel; Zingman, Leonid V.; Hodgson-Zingman, Denice M.

2013-01-01

Cardiac ATP-sensitive potassium (KATP) channels are key sensors and effectors of the metabolic status of cardiomyocytes. Alteration in their expression impacts their effectiveness in maintaining cellular energy homeostasis and resistance to injury. We sought to determine how activation of calcium/calmodulin-dependent protein kinase II (CaMKII), a central regulator of calcium signaling, translates into reduced membrane expression and current capacity of cardiac KATP channels. We used real-time monitoring of KATP channel current density, immunohistochemistry, and biotinylation studies in isolated hearts and cardiomyocytes from wild-type and transgenic mice as well as HEK cells expressing wild-type and mutant KATP channel subunits to track the dynamics of KATP channel surface expression. Results showed that activation of CaMKII triggered dynamin-dependent internalization of KATP channels. This process required phosphorylation of threonine at 180 and 224 and an intact 330YSKF333 endocytosis motif of the KATP channel Kir6.2 pore-forming subunit. A molecular model of the μ2 subunit of the endocytosis adaptor protein, AP2, complexed with Kir6.2 predicted that μ2 docks by interaction with 330YSKF333 and Thr-180 on one and Thr-224 on the adjacent Kir6.2 subunit. Phosphorylation of Thr-180 and Thr-224 would favor interactions with the corresponding arginine- and lysine-rich loops on μ2. We concluded that calcium-dependent activation of CaMKII results in phosphorylation of Kir6.2, which promotes endocytosis of cardiac KATP channel subunits. This mechanism couples the surface expression of cardiac KATP channels with calcium signaling and reveals new targets to improve cardiac energy efficiency and stress resistance. PMID:23223335

Urologic laser types and instrumentation.

PubMed

Natalin, Ricardo A; Phillips, Courtney K; Clayman, Ralph V; Landman, Jaime

2008-11-01

Though the primary role of lasers in urology has always been in the treatment of urolithiasis, there are several other indications for their use. There are many different types of lasers currently available, each with unique properties conducive to treating certain disorders. As such, it is critical that today's urologist understands each laser's characteristics in order to optimize patient selection and treatment. The lasers which are primarily used in urologic applications include the carbon dioxide (CO2) laser; the Neodymium:Yttrium-Aluminum-Garnet (Nd:YAG); the Potassium Titanyl Phosphate (KTP) laser and the Holmium:YAG (Ho:YAG) laser. This review focuses on the unique characteristics of each of these lasers as well as the instrumentation needed utilize and deploy these tools in the urinary tract.

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction.

PubMed

Cho, Jae Hyung; Zhang, Rui; Kilfoil, Peter J; Gallet, Romain; de Couto, Geoffrey; Bresee, Catherine; Goldhaber, Joshua I; Marbán, Eduardo; Cingolani, Eugenio

2017-11-21

Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression. After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats ( P <0.001 versus controls). The arrhythmogenicity index was increased ( P <0.001) and the corrected QT interval on ECG was prolonged ( P <0.001) in HFpEF rats. Optical mapping of HFpEF hearts demonstrated prolonged action potentials ( P <0.05) and multiple reentry circuits during induced VA. Single-cell recordings of cardiomyocytes isolated from HFpEF rats confirmed a delay of repolarization ( P =0.001) and revealed downregulation of transient outward potassium current ( I to ; P <0.05). The rapid components of the delayed rectifier potassium current ( I Kr ) and the inward rectifier potassium current ( I K1 ) were also downregulated ( P <0.05), but the current densities were much lower than for I to . In accordance with the reduction of I to , both Kcnd3 transcript and Kv4.3 protein levels were decreased in HFpEF rat hearts. Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QT prolongation, delayed repolarization from downregulation of potassium currents, and multiple reentry circuits during VA. Our findings are consistent with the hypothesis that potassium current downregulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death. © 2017 American Heart Association, Inc.

Alterations of sodium and potassium channels of RGCs in RCS rat with the development of retinal degeneration.

PubMed

Chen, Zhongshan; Song, Yanping; Yao, Junping; Weng, Chuanhuang; Yin, Zheng Qin

2013-11-01

All know that retinitis pigmentosa (RP) is a group of hereditary retinal degenerative diseases characterized by progressive dysfunction of photoreceptors and associated with progressive cells loss; nevertheless, little is known about how rods and cones loss affects the surviving inner retinal neurons and networks. Retinal ganglion cells (RGCs) process and convey visual information from retina to visual centers in the brain. The healthy various ion channels determine the normal reception and projection of visual signals from RGCs. Previous work on the Royal College of Surgeons (RCS) rat, as a kind of classical RP animal model, indicated that, at late stages of retinal degeneration in RCS rat, RGCs were also morphologically and functionally affected. Here, retrograde labeling for RGCs with Fluorogold was performed to investigate the distribution, density, and morphological changes of RGCs during retinal degeneration. Then, patch clamp recording, western blot, and immunofluorescence staining were performed to study the channels of sodium and potassium properties of RGCs, so as to explore the molecular and proteinic basis for understanding the alterations of RGCs membrane properties and firing functions. We found that the resting membrane potential, input resistance, and capacitance of RGCs changed significantly at the late stage of retinal degeneration. Action potential could not be evoked in a part of RGCs. Inward sodium current and outward potassium current recording showed that sodium current was impaired severely but only slightly in potassium current. Expressions of sodium channel protein were impaired dramatically at the late stage of retinal degeneration. The results suggested that the density of RGCs decreased, process ramification impaired, and sodium ion channel proteins destructed, which led to the impairment of electrophysiological functions of RGCs and eventually resulted in the loss of visual function.

Sodium Zirconium Cyclosilicate (ZS-9): A Novel Agent for the Treatment of Hyperkalemia.

PubMed

Linder, Kristin E; Krawczynski, Michelle A; Laskey, Dayne

2016-08-01

Hyperkalemia is a potentially life-threatening electrolyte abnormality that may be caused by select medications, underlying organ dysfunction, or alterations in potassium homeostasis. Treatment for this condition has remained largely unchanged since the release of sodium polystyrene sulfonate (SPS) in 1958. Despite its widespread use, the safety and efficacy of SPS remains controversial. Two novel potassium-binding resins have emerged in recent years. Patiromer was the first of these to receive U.S. Food and Drug Administration approval for the treatment of hyperkalemia in October 2015. A second potassium-binding resin, a zirconium cyclosilicate currently known as ZS-9, may provide yet another alternative to the archetypal treatment with SPS. ZS-9 is an orally administered nonabsorbed inorganic compound that selectively binds potassium ions in vivo. Two phase III multicenter, randomized, placebo-controlled, double-blind trials have evaluated ZS-9 for the treatment of acute hyperkalemia. In this review, we discuss the pharmacology, clinical efficacy, safety, and potential place in therapy of ZS-9 for the enhanced elimination of potassium in the setting of hyperkalemia. © 2016 Pharmacotherapy Publications, Inc.

Advances in treatment of hyperkalemia in chronic kidney disease.

PubMed

Sarafidis, Pantelis A; Georgianos, Panagiotis I; Bakris, George L

2015-01-01

Hyperkalemia is a frequent electrolyte disorder associated with life-threatening cardiac arrhythmias and sudden death. Patients prone to hyperkalemia have chronic kidney disease (CKD) either alone or in conjunction with diabetes or heart failure (HF). Although agents inhibiting the renin-angiotensin-aldosterone-system (RAAS) are currently the first-line treatments toward cardio- and nephroprotection, their administration often leads to potassium elevation in such patients and results in high rates of treatment discontinuation. This article provides an overview of factors interfering with potassium homeostasis and discusses emerging potassium-lowering therapies for long-term management of hyperkalemia. In recent randomized clinical studies, two new oral potassium-exchanging compounds, patiromer and sodium zirconium cyclosilicate, were shown to effectively normalize elevated serum potassium and chronically maintain potassium homeostasis in hyperkalemic patients treated with RAAS blockers. Both agents exhibit good tolerability and were not associated with serious adverse effects. Although additional research is required, these drugs are promising for lowering the risk of incident hyperkalemia associated with RAAS blockade use in people with diabetes or HF who have CKD. They also provide the opportunity to test whether patients who could not previously receive RAAS blockade may benefit from their cardio- and renoprotective effects.

Fludrocortisone therapy for persistent hyperkalaemia.

PubMed

Dobbin, S J H; Petrie, J R; Lean, M E J; McKay, G A

2017-07-01

Type 4 renal tubular acidosis causes hyperkalaemia, for which diabetes and medications commonly used in this patient group are aetiological factors. Here we describe the novel use of fludrocortisone in this difficult condition. A 55-year-old woman with complex co-morbidities, including Type 2 diabetes (HbA 1c 37 mmol/mol 5.5%), was admitted with renal failure. Bloods on admission: eGFR 25 ml/min, creatinine 184 ?mol/L, urea 35.9 mmol/L, sodium 128 mmol/L, potassium 5.6 mmol/L, bicarbonate 15 mmol/L, and albumin 30 g/L. Her admission was prolonged, complicated by hospital-acquired sepsis (lower respiratory tract, urinary tract, and infected leg ulcers), poor venous access and severe depression. She had recurrent hyperkalaemia and deteriorating renal function, from presumed Type 4 renal tubular acidosis and excessive fluid losses from leg ulcers. Her renal function recurrently deteriorated, despite conventional treatment methods. After 69 days, she was commenced on fludrocortisone 50 mcg/day. Her renal function and serum potassium stabilized and she was discharged with potassium 4.3 mmol/L, eGFR 42 ml/min, and bicarbonate 23 mmol/L. She has remained stable on this treatment, without requiring further hospital admission for over 6 months, with eGFR 40 ml/min, and potassium 5.5 mmol/L, and albumin 26 g/L. This woman was presumed to have Type 4 renal tubular acidosis and recurrent hyperkalaemia due to renal insufficiency, in the context of underlying diabetes and chronic kidney disease, which was poorly responsive to conventional management. There is limited evidence for using fludrocortisone in this setting. Our case suggests that fludrocortisone might offer a novel therapeutic strategy when conventional management is not working. © 2017 Diabetes UK.

Photobiomodulation partially rescues visual cortical neurons from cyanide-induced apoptosis.

PubMed

Liang, H L; Whelan, H T; Eells, J T; Meng, H; Buchmann, E; Lerch-Gaggl, A; Wong-Riley, M

2006-05-12

Near-infrared light via light-emitting diode treatment has documented therapeutic effects on neurons functionally inactivated by tetrodotoxin or methanol intoxication. Light-emitting diode pretreatment also reduced potassium cyanide-induced cell death, but the mode of death via the apoptotic or necrotic pathway was unclear. The current study tested our hypothesis that light-emitting diode rescues neurons from apoptotic cell death. Primary neuronal cultures from postnatal rat visual cortex were pretreated with light-emitting diode for 10 min at a total energy density of 30 J/cm2 before exposing to potassium cyanide for 28 h. With 100 or 300 microM potassium cyanide, neurons died mainly via the apoptotic pathway, as confirmed by electron microscopy, Hoechst 33258, single-stranded DNA, Bax, and active caspase-3. In the presence of caspase inhibitor I, the percentage of apoptotic cells in 300microM potassium cyanide was significantly decreased. Light-emitting diode pretreatment reduced apoptosis from 36% to 17.9% (100 microM potassium cyanide) and from 58.9% to 39.6% (300 microM potassium cyanide), representing a 50.3% and 32.8% reduction, respectively. Light-emitting diode pretreatment significantly decreased the expression of caspase-3 elicited by potassium cyanide. It also reversed the potassium cyanide-induced increased expression of Bax and decreased expression of Bcl-2 to control levels. Moreover, light-emitting diode decreased the intensity of 5-(and -6) chloromethy-2', 7-dichlorodihydrofluorescein diacetate acetyl ester, a marker of reactive oxygen species, in neurons exposed to 300 microM potassium cyanide. These results indicate that light-emitting diode pretreatment partially protects neurons against cyanide-induced caspase-mediated apoptosis, most likely by decreasing reactive oxygen species production, down-regulating pro-apoptotic proteins and activating anti-apoptotic proteins, as well as increasing energy metabolism in neurons as reported previously.

Effects of protein-protein interactions and ligand binding on the ion permeation in KCNQ1 potassium channel.

PubMed

Jalily Hasani, Horia; Ganesan, Aravindhan; Ahmed, Marawan; Barakat, Khaled H

2018-01-01

The voltage-gated KCNQ1 potassium ion channel interacts with the type I transmembrane protein minK (KCNE1) to generate the slow delayed rectifier (IKs) current in the heart. Mutations in these transmembrane proteins have been linked with several heart-related issues, including long QT syndromes (LQTS), congenital atrial fibrillation, and short QT syndrome. Off-target interactions of several drugs with that of KCNQ1/KCNE1 ion channel complex have been known to cause fatal cardiac irregularities. Thus, KCNQ1/KCNE1 remains an important avenue for drug-design and discovery research. In this work, we present the structural and mechanistic details of potassium ion permeation through an open KCNQ1 structural model using the combined molecular dynamics and steered molecular dynamics simulations. We discuss the processes and key residues involved in the permeation of a potassium ion through the KCNQ1 ion channel, and how the ion permeation is affected by (i) the KCNQ1-KCNE1 interactions and (ii) the binding of chromanol 293B ligand and its derivatives into the complex. The results reveal that interactions between KCNQ1 with KCNE1 causes a pore constriction in the former, which in-turn forms small energetic barriers in the ion-permeation pathway. These findings correlate with the previous experimental reports that interactions of KCNE1 dramatically slows the activation of KCNQ1. Upon ligand-binding onto the complex, the energy-barriers along ion permeation path are more pronounced, as expected, therefore, requiring higher force in our steered-MD simulations. Nevertheless, pulling the ion when a weak blocker is bound to the channel does not necessitate high force in SMD. This indicates that our SMD simulations have been able to discern between strong and week blockers and reveal their influence on potassium ion permeation. The findings presented here will have some implications in understanding the potential off-target interactions of the drugs with the KCNQ1/KCNE1 channel that lead to cardiotoxic effects.

Hyperkalemia of the blood-primed ECLS circuit does not result in post-initiation hyperkalemia in infants < 10 kg.

PubMed

Fleming, Geoffrey M; Remenapp, Robert T; Bartlett, Robert H; Annich, Gail M

2006-05-01

To assess the risk of hyperkalemia with blood-primed extracorporeal life support (ECLS) circuits in infants < 10 kg. Retrospective cohort study of all neonatal and pediatric patients < 10 kg placed on ECLS from May 1998 to April 2001. Data collection including patient weight, patient potassium levels pre- and post-initiation of ECLS, potassium level of the primed ECLS circuit, age of the packed red blood cell (PRBC) unit, type of preservative, and preservative reduction status. Seventy-six circuits were available for the analysis. The age of the PRBC unit and preservative reduction status significantly affected the potassium level of the primed ECLS circuit. Multivariate linear regression analysis showed no significant effect on the post-ECLS initiation patient potassium level with respect to the PRBC age, the preservative reduction status, the patient potassium level prior to ECLS initiation, and the potassium level of the primed ECLS circuit. Initiation of ECLS in infants < 10 kg should not be delayed unnecessarily to perform preservative reduction or to utilize PRBC units of a specific age, as hyperkalemia of the primed ECLS circuit is not associated with systemic hyperkalemia in the patient post-initiation of ECLS.

Age-dependent axonal expression of potassium channel proteins during development in mouse hippocampus.

PubMed

Prüss, Harald; Grosse, Gisela; Brunk, Irene; Veh, Rüdiger W; Ahnert-Hilger, Gudrun

2010-03-01

The development of the hippocampal network requires neuronal activity, which is shaped by the differential expression and sorting of a variety of potassium channels. Parallel to their maturation, hippocampal neurons undergo a distinct development of their ion channel profile. The age-dependent dimension of ion channel occurrence is of utmost importance as it is interdependently linked to network formation. However, data regarding the exact temporal expression of potassium channels during postnatal hippocampal development are scarce. We therefore studied the expression of several voltage-gated potassium channel proteins during hippocampal development in vivo and in primary cultures, focusing on channels that were sorted to the axonal compartment. The Kv1.1, Kv1.2, Kv1.4, and Kv3.4 proteins showed a considerable temporal variation of axonal localization among neuronal subpopulations. It is possible, therefore, that hippocampal neurons possess cell type-specific mechanisms for channel compartmentalization. Thus, age-dependent axonal sorting of the potassium channel proteins offers a new approach to functionally distinguish classes of hippocampal neurons and may extend our understanding of hippocampal circuitry and memory processing.

Frequency of laboratory measurement and hyperkalaemia in hospitalised patients using serum potassium concentration increasing drugs.

PubMed

Uijtendaal, Esther V; Zwart-van Rijkom, Jeannette E F; van Solinge, Wouter W; Egberts, Toine C G

2011-09-01

Although, drug-drug interactions (DDIs) between potassium-increasing drugs (PIDs) are known risk factors for developing hyperkalaemia, not much is known about their risk and management strategies during hospitalisation. This study examines the frequency of serum potassium measurements and hyperkalaemia in hospitalised patients, based on the use of one or more PIDs, and the determinants thereof. Adult patients hospitalised in the University Medical Centre Utrecht between 2006 and 2008 were included in this cross-sectional study. The frequency of serum potassium measurements and of hyperkalaemia were compared between patients using only one PID at a time (monotherapy group) and patients using two or more PIDs concomitantly (interaction group). The determinants studied were renal failure, diabetes mellitus, use of diuretics, type of DDI, start of the PIDs within the hospital versus continued home medication and medical speciality. Serum potassium was measured more frequently in the interaction group than in the monotherapy group [67 vs. 56%; relative risk (RR) 1.19, 95% confidence interval (CI) 1.14-1.24] and the risk of hyperkalaemia was also increased in the interaction group (9.9 vs. 5.9%, RR 1.7, 95% CI 1.3-2.1). The combination of potassium-sparing diuretics plus a potassium supplement, start of the PID within the hospital and hospitalisation in non-internal medicine departments was associated with higher relative risk estimates for hyperkalaemia. Among our patient cohort, even when physicians received a direct pop-up to monitor serum potassium levels when prescribing two PIDs concomitantly, serum potassium levels were not measured in 33% of patients, and 10% of patients developed hyperkalaemia. Improved management strategies and/or clinical decision-support systems are needed to decrease the frequency of hyperkalaemia following DDIs.

Recent Advances in the Pathogenesis and Drug Action in Periodic Paralyses and Related Channelopathies

PubMed Central

Tricarico, Domenico; Camerino, Diana Conte

2011-01-01

The periodic paralysis (PP) are rare autosomal-dominant disorders associated to mutations in the skeletal muscle sodium, calcium, and potassium channel genes characterized by muscle fiber depolarization with un-excitability, episodes of weakness with variations in serum potassium concentrations. Recent advances in thyrotoxic PP and hypokalemic PP (hypoPP) confirm the involvement of the muscle potassium channels in the pathogenesis of the diseases and their role as target of action for drugs of therapeutic interest. The novelty in the gating pore currents theory help to explain the disease symptoms, and open the possibility to more specifically target the disease. It is now known that the fiber depolarization in the hypoPP is due to an unbalance between the novel identified depolarizing gating pore currents (Igp) carried by protons or Na+ ions flowing through aberrant alternative pathways of the mutant subunits and repolarizing inwardly rectifying potassium channel (Kir) currents which also includes the ATP-sensitive subtype. Abnormal activation of the Igp or deficiency in the Kir channels predispose to fiber depolarization. One pharmacological strategy is based on blocking the Igp without affecting normal channel gating. It remains safe and effective the proposal of targeting the KATP, Kir channels, or BK channels by drugs capable to specifically open at nanomolar concentrations the skeletal muscle subtypes with less side effects. PMID:21687503

[Development and validation of an analytical method to quantify residues of cleaning products able to inactivate prion].

PubMed

Briot, T; Robelet, A; Morin, N; Riou, J; Lelièvre, B; Lebelle-Dehaut, A-V

2016-07-01

In this study, a novel analytical method to quantify prion inactivating detergent in rinsing waters coming from the washer-disinfector of a hospital sterilization unit has been developed. The final aim was to obtain an easy and functional method in a routine hospital process which does not need the cleaning product manufacturer services. An ICP-MS method based on the potassium dosage of the washer-disinfector's rinsing waters was developed. Potassium hydroxide is present on the composition of the three prion inactivating detergent currently on the French market. The detergent used in this study was the Actanios LDI(®) (Anios laboratories). A Passing and Bablok regression compares concentrations measured with this developed method and with the HPLC-UV manufacturer method. According to results obtained, the developed method is easy to use in a routine hospital process. The Passing and Bablok regression showed that there is no statistical difference between the two analytical methods during the second rinsing step. Besides, both methods were linear on the third rinsing step, with a 1.5ppm difference between the concentrations measured for each method. This study shows that the ICP-MS method developed is nonspecific for the detergent, but specific for the potassium element which is present in all prion inactivating detergent currently on the French market. This method should be functional for all the prion inactivating detergent containing potassium, if the sensibility of the method is sufficient when the potassium concentration is very low in the prion inactivating detergent formulation. Copyright © 2016. Published by Elsevier Masson SAS.

Skin decontamination efficacy of potassium ketoxime on rabbits exposed to sulfur mustard.

PubMed

Sun, Jing-Hai; Sun, Pei-Pei; Zheng, Wei; Han, Song; Ying, Ying; Liu, Hong-Yan; Zhang, Cheng; Zhao, Bao-Quan; Zuo, Guo-Min; Lu, Hong; Zhong, Yu-Xu

2015-03-01

The chemical weapon sulfur mustard (SM) is a blister agent, and currently, there is no effective antidote. To evaluate the decontamination efficacy of potassium ketoxime against SM and preliminarily elucidate its decontamination mechanism. Potassium ketoxime reacted with SM, and SM residues were tested at different time intervals by T-135 colorimetry after the reaction. Rabbit skin was topically exposed to 2 mg/cm(2) SM, treated with potassium ketoxime 1 min later, and observed after 6, 12, and 24 h. Gas chromatography-mass spectroscopy was employed to screen and identify the main products of potassium ketoxime decontamination of SM. Potassium ketoxime had a great effect against SM contamination. With a mass ratio of decontaminant: SM of 50:1, decontamination rates against SM were 87.5% after 30 s, 95.9% after 1 min, and 99.0% after 5 min. Fifteen minutes after exposure to SM, the untreated group showed clear erythema lesions, whereas the experimental group showed no clear erythema lesions within 6 h. After 12 and 24 h, the areas of damaged skin in the experimental group were 0.038 and 0.125 cm(2), respectively, compared with 2.21 and 2.65 cm(2) in the control group. Histopathological analysis revealed that treatment with potassium ketoxime also reduced inflammation-induced damage. The results of this study indicate that potassium ketoxime reacted rapidly and completely with SM, and thus, it was found to be a suitable and effective skin decontaminant against SM. The decontamination reaction mechanism is mainly related to nucleophilic substitution.

Clinical Aspects of Type-1 Long-QT Syndrome by Location, Coding Type, and Biophysical Function of Mutations Involving the KCNQ1 Gene

PubMed Central

Moss, Arthur J.; Shimizu, Wataru; Wilde, Arthur A.M.; Towbin, Jeffrey A.; Zareba, Wojciech; Robinson, Jennifer L.; Qi, Ming; Vincent, G. Michael; Ackerman, Michael J.; Kaufman, Elizabeth S.; Hofman, Nynke; Seth, Rahul; Kamakura, Shiro; Miyamoto, Yoshihiro; Goldenberg, Ilan; Andrews, Mark L.; McNitt, Scott

2012-01-01

Background Type-1 long-QT syndrome (LQTS) is caused by loss-of-function mutations in the KCNQ1-encoded IKs cardiac potassium channel. We evaluated the effect of location, coding type, and biophysical function of KCNQ1 mutations on the clinical phenotype of this disorder. Methods and Results We investigated the clinical course in 600 patients with 77 different KCNQ1 mutations in 101 proband-identified families derived from the US portion of the International LQTS Registry (n=425), the Netherlands’ LQTS Registry (n=93), and the Japanese LQTS Registry (n=82). The Cox proportional hazards survivorship model was used to evaluate the independent contribution of clinical and genetic factors to the first occurrence of time-dependent cardiac events from birth through age 40 years. The clinical characteristics, distribution of mutations, and overall outcome event rates were similar in patients enrolled from the 3 geographic regions. Biophysical function of the mutations was categorized according to dominant-negative (>50%) or haploinsufficiency (≤50%) reduction in cardiac repolarizing IKs potassium channel current. Patients with transmembrane versus C-terminus mutations (hazard ratio, 2.06; P<0.001) and those with mutations having dominant-negative versus haploinsufficiency ion channel effects (hazard ratio, 2.26; P<0.001) were at increased risk for cardiac events, and these genetic risks were independent of traditional clinical risk factors. Conclusions This genotype–phenotype study indicates that in type-1 LQTS, mutations located in the transmembrane portion of the ion channel protein and the degree of ion channel dysfunction caused by the mutations are important independent risk factors influencing the clinical course of this disorder. PMID:17470695

Delayed rectifier and A-type potassium channels associated with Kv 2.1 and Kv 4.3 expression in embryonic rat neural progenitor cells.

PubMed

Smith, Dean O; Rosenheimer, Julie L; Kalil, Ronald E

2008-02-13

Because of the importance of voltage-activated K(+) channels during embryonic development and in cell proliferation, we present here the first description of these channels in E15 rat embryonic neural progenitor cells derived from the subventricular zone (SVZ). Activation, inactivation, and single-channel conductance properties of recorded progenitor cells were compared with those obtained by others when these Kv gene products were expressed in oocytes. Neural progenitor cells derived from the subventricular zone of E15 embryonic rats were cultured under conditions that did not promote differentiation. Immunocytochemical and Western blot assays for nestin expression indicated that almost all of the cells available for recording expressed this intermediate filament protein, which is generally accepted as a marker for uncommitted embryonic neural progenitor cells. However, a very small numbers of the cells expressed GFAP, a marker for astrocytes, O4, a marker for immature oligodendrocytes, and betaIII-tubulin, a marker for neurons. Using immunocytochemistry and Western blots, we detected consistently the expression of Kv2.1, and 4.3. In whole-cell mode, we recorded two outward currents, a delayed rectifier and an A-type current. We conclude that Kv2.1, and 4.3 are expressed in E15 SVZ neural progenitor cells, and we propose that they may be associated with the delayed-rectifier and the A-type currents, respectively, that we recorded. These results demonstrate the early expression of delayed rectifier and A-type K(+) currents and channels in embryonic neural progenitor cells prior to the differentiation of these cells.

PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells.

PubMed

Haick, Jennifer M; Brueggemann, Lioubov I; Cribbs, Leanne L; Denning, Mitchell F; Schwartz, Jeffrey; Byron, Kenneth L

2017-06-01

Kv7 potassium channels have recently been found to be expressed and functionally important for relaxation of airway smooth muscle. Previous research suggests that native Kv7 currents are inhibited following treatment of freshly isolated airway smooth muscle cells with bronchoconstrictor agonists, and in intact airways inhibition of Kv7 channels is sufficient to induce bronchiolar constriction. However, the mechanism by which Kv7 currents are inhibited by bronchoconstrictor agonists has yet to be elucidated. In the present study, native Kv7 currents in cultured human trachealis smooth muscle cells (HTSMCs) were observed to be inhibited upon treatment with histamine; inhibition of Kv7 currents was associated with membrane depolarization and an increase in cytosolic Ca 2+ ([Ca 2+ ] cyt ). The latter response was inhibited by verapamil, a blocker of L-type voltage-sensitive Ca 2+ channels (VSCCs). Protein kinase C (PKC) has been implicated as a mediator of bronchoconstrictor actions, although the targets of PKC are not clearly established. We found that histamine treatment significantly and dose-dependently suppressed currents through overexpressed wild-type human Kv7.5 (hKv7.5) channels in cultured HTSMCs, and this effect was inhibited by the PKC inhibitor Ro-31-8220 (3 µM). The PKC-dependent suppression of hKv7.5 currents corresponded with a PKC-dependent increase in hKv7.5 channel phosphorylation. Knocking down or inhibiting PKCα, or mutating hKv7.5 serine 441 to alanine, abolished the inhibitory effects of histamine on hKv7.5 currents. These findings provide the first evidence linking PKC activation to suppression of Kv7 currents, membrane depolarization, and Ca 2+ influx via L-type VSCCs as a mechanism for histamine-induced bronchoconstriction. Copyright © 2017 the American Physiological Society.

A Small Potassium Current in AgRP/NPY Neurons Regulates Feeding Behavior and Energy Metabolism.

PubMed

He, Yanlin; Shu, Gang; Yang, Yongjie; Xu, Pingwen; Xia, Yan; Wang, Chunmei; Saito, Kenji; Hinton, Antentor; Yan, Xiaofeng; Liu, Chen; Wu, Qi; Tong, Qingchun; Xu, Yong

2016-11-08

Neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons are dynamically regulated by energy status and coordinate appropriate feeding behavior to meet nutritional demands. However, intrinsic mechanisms that regulate AgRP/NPY neural activities during the fed-to-fasted transition are not fully understood. We found that AgRP/NPY neurons in satiated mice express high levels of the small-conductance calcium-activated potassium channel 3 (SK3) and are inhibited by SK3-mediated potassium currents; on the other hand, food deprivation suppresses SK3 expression in AgRP/NPY neurons, and the decreased SK3-mediated currents contribute to fasting-induced activation of these neurons. Genetic mutation of SK3 specifically in AgRP/NPY neurons leads to increased sensitivity to diet-induced obesity, associated with chronic hyperphagia and decreased energy expenditure. Our results identify SK3 as a key intrinsic mediator that coordinates nutritional status with AgRP/NPY neural activities and animals' feeding behavior and energy metabolism. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

[Lead compound optimization strategy(5) – reducing the hERG cardiac toxicity in drug development].

PubMed

Zhou, Sheng-bin; Wang, Jiang; Liu, Hong

2016-10-01

The potassium channel encoded by the human ether-a-go-go related gene(hERG) plays a very important role in the physiological and pathological processes in human. hERG potassium channel determines the outward currents which facilitate the repolarization of the myocardial cells. Some drugs were withdrawn from the market for the serious side effect of long QT interval and arrhythmia due to blockade of hERG channel. The strategies for lead compound optimization are to reduce inhibitory activity of hERG potassium channel and decrease cardiac toxicity. These methods include reduction of lipophilicity and basicity of amines, introduction of hydroxyl and acidic groups, and restricting conformation.

Role of dietary salt and potassium intake in cardiovascular health and disease: a review of the evidence.

PubMed

Aaron, Kristal J; Sanders, Paul W

2013-09-01

The objective of this review was to provide a synthesis of the evidence on the effect of dietary salt and potassium intake on population blood pressure, cardiovascular disease, and mortality. Dietary guidelines and recommendations are outlined, current controversies regarding the evidence are discussed, and recommendations are made on the basis of the evidence. Designed search strategies were used to search various databases for available studies. Randomized trials of the effect of dietary salt intake reduction or increased potassium intake on blood pressure, target organ damage, cardiovascular disease, and mortality were included. Fifty-two publications from January 1, 1990, to January 31, 2013, were identified for inclusion. Consideration was given to variations in the search terms used and the spelling of terms so that studies were not overlooked, and search terms took the following general form: (dietary salt or dietary sodium or [synonyms]) and (dietary potassium or [synonyms]) and (blood pressure or hypertension or vascular disease or heart disease or chronic kidney disease or stroke or mortality or [synonyms]). Evidence from these studies demonstrates that high salt intake not only increases blood pressure but also plays a role in endothelial dysfunction, cardiovascular structure and function, albuminuria and kidney disease progression, and cardiovascular morbidity and mortality in the general population. Conversely, dietary potassium intake attenuates these effects, showing a linkage to reduction in stroke rates and cardiovascular disease risk. Various subpopulations, such as overweight and obese individuals and aging adults, exhibit greater sensitivity to the effects of reduced salt intake and may gain the most benefits. A diet that includes modest salt restriction while increasing potassium intake serves as a strategy to prevent or control hypertension and decrease cardiovascular morbidity and mortality. Thus, the body of evidence supports population-wide sodium intake reduction and recommended increases in dietary potassium intake as outlined by current guidelines as an essential public health effort to prevent kidney disease, stroke, and cardiovascular disease. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2016-01-18

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

Serum Sodium and Potassium Levels in Cerebro-vascular Accident Patients.

PubMed

Farahmand, Farahmand; Choobi Anzali, Babak; Heshmat, Ramin; Ghafouri, Hamed-Basir; Hamedanchi, Sepehr

2013-05-01

We aim to assess serum sodium and potassium levels in patients with different types of cerebro-vascular accidents (CVA) in comparison to control group. A comparative cross-sectional study conducted on patients admitted to the emergency department from January to August 2012. Control group consisted of patients admitted to emergency department due to common cold, urinary tract infection, low back pain, cluster, and tension headache or migraine. Serum sodium and potassium levels were measured via standard laboratory methods. There were 77 patients in control group and 78 in CVA group. Forty nine patients from the CVA group had ischemic CVA, 11 had hemorrhagic CVA and 18 suffered a transient ischemic attack (TIA). Serum sodium level in control group was significantly lower than in patients with TIA, ischemic CVA, and hemorrhagic CVA (P < 0.001). Serum potassium level in control group was higher than patients with TIA, ischemic CVA, and hemorrhagic CVA (P < 0.001). Patients with hemorrhagic CVA showed significantly lower serum potassium level than patients with TIA and ischemic CVA (P < 0.001). Correspondingly, it was observed that serum sodium to potassium ratio was higher in patients with TIA, ischemic CVA, and hemorrhagic CVA (P < 0.001). In patients with hemorrhagic CVA serum sodium to potassium ratio was higher when compared to patients with TIA and ischemic CVA (P < 0.001). This study shows that higher serum sodium and lower serum potassium level may be associated with higher incidence of CVA. Further studies are paramount to elucidate the role of serum electrolyte levels in vascular events.

Inward rectifier potassium channels control rotor frequency in ventricular fibrillation.

PubMed

Jalife, José

2009-11-01

Ventricular fibrillation (VF) is the most important cause of sudden cardiac death. While traditionally thought to result from random activation of the ventricles by multiple independent wavelets, recent evidence suggests that VF may be determined by the sustained activation of a relatively small number of reentrant sources. In addition, recent experimental data in various species as well as computer simulations have provided important clues about its ionic and molecular mechanisms, particularly in regards to the role of potassium currents in such mechanisms. The results strongly argue that the inward rectifier current, I(K1,) is an important current during functional reentry because it mediates the electrotonic interactions between the unexcited core and its immediate surroundings. In addition, I(K1) is a stabilizer of reentry due to its ability to shorten action potential duration and reduce conduction velocity near the center of rotation. Increased I(K1) prevents wave front-wave tail interactions and thus averts rotor destabilization and breakup. Other studies have shown that while the slow component of the delayed rectifier potassium current I(Ks) does not significantly modify rotor frequency or stability, it plays a major role in postrepolarization refractoriness and wave break formation. Therefore, the interplay between I(K1) and the rapid sodium inward current (I(Na)) is a major factor in the control of cardiac excitability and thus the stability and frequency of reentry, while I(Ks) is an important determinant of fibrillatory conduction.

Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

PubMed Central

Joiner, C H; Platt, O S; Lux, S E

1986-01-01

The mechanism by which sickle cells and xerocytic red cells become depleted of cations in vivo has not been identified previously. Both types of cells exhibit elevated permeabilities to sodium and potassium, in the case of sickle cells, when deoxygenated. The ouabain-insensitive fluxes of sodium and potassium were equivalent, however, in both cell types under these conditions. When incubated 18 hours in vitro, sickle cells lost cations but only when deoxygenated. This cation depletion was blocked by ouabain, removal of external potassium, or pretreatment with 4,4'-diisothiocyanostilbene-2,2'-disulfonate, which blocks the increase in cation permeability induced by deoxygenation. The loss of cation exhibited by oxygenated xerocytes similarly incubated was also blocked by ouabain. These data support the hypothesis that the elevated "passive" cation fluxes of xerocytes and deoxygenated sickle cells are not directly responsible for cation depletion of these cells; rather, these pathologic leaks interact with the sodium pump to produce a net loss of cellular cation. PMID:2430999

Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

PubMed

Joiner, C H; Platt, O S; Lux, S E

1986-12-01

The mechanism by which sickle cells and xerocytic red cells become depleted of cations in vivo has not been identified previously. Both types of cells exhibit elevated permeabilities to sodium and potassium, in the case of sickle cells, when deoxygenated. The ouabain-insensitive fluxes of sodium and potassium were equivalent, however, in both cell types under these conditions. When incubated 18 hours in vitro, sickle cells lost cations but only when deoxygenated. This cation depletion was blocked by ouabain, removal of external potassium, or pretreatment with 4,4'-diisothiocyanostilbene-2,2'-disulfonate, which blocks the increase in cation permeability induced by deoxygenation. The loss of cation exhibited by oxygenated xerocytes similarly incubated was also blocked by ouabain. These data support the hypothesis that the elevated "passive" cation fluxes of xerocytes and deoxygenated sickle cells are not directly responsible for cation depletion of these cells; rather, these pathologic leaks interact with the sodium pump to produce a net loss of cellular cation.

Diet, weight, cytokines and bone health in postmenopausal women.

PubMed

Gunn, C A; Weber, J L; Kruger, M C

2014-05-01

To investigate diet and nutrition-related factors associated with bone loss in a group of postmenopausal (PM) women. Nutritional intake, inflammatory markers and body composition (weight, body mass index, fat/lean mass) were analysed for associations with bone mineral density (BMD). A cross sectional study examining correlations between BMD (Duel-energy X ray absorptiometry; (DXA) and dietary intake (3-day diaries), body composition and plasma bone and inflammatory markers: C-terminal telopeptide of type I collagen (CTX) and procollagen type I N propeptide (P1NP), C- reactive protein (CRP), interleukin 6 and 10 (IL-6, IL-10), tumour necrosis factor (TNF) and osteoprotegerin (OPG). Community dwelling women from the Auckland, Hawke's Bay and Manawatu regions in New Zealand. 142 healthy, PM women aged 50-70 years. OPG (per kilogram fat mass) was increased in women with osteoporosis (p<0.001) compared to groups classified with normal BMD and osteopenia. Protein, vitamin B12, zinc, potassium and dairy intake were all positively correlated with higher BMD while dairy and potassium intakes also inversely correlated with CTX. Body composition (weight, BMI and fat/lean mass) had strong positive associations with BMD. Multiple regression analysis showed body weight, potassium and dairy intake were predictors of increased BMD in PM women and explained 39% (r2=0.39, p< 0.003) of variance. BMD was negatively correlated with OPG and positively with weight, dairy and potassium intake. This study highlights the importance of maintaining adequate body weight and emphasising dairy and potassium predominantly sourced from fruit/vegetables to reduce bone loss at midlife.

Modulation of intracellular Ca2+ via L-type calcium channels in heart cells by the autoantibody directed against the second extracellular loop of the alpha1-adrenoceptors.

PubMed

Bkaily, Ghassan; El-Bizri, Nesrine; Bui, Michel; Sukarieh, Rami; Jacques, Danielle; Fu, Michael L X

2003-03-01

The effects of methoxamine, a selective alpha1-adrenergic receptor agonist, and the autoantibody directed against the second extracellular loop of alpha1-adrenoceptors were studied on intracellular free Ca2+ levels using confocal microscopy and ionic currents using the whole-cell patch clamp technique in single cells of 10-day-old embryonic chick and 20-week-old fetal human hearts. We observed that like methoxamine, the autoantibody directed against the second extracellular loop of alpha1-adrenoreceptors significantly increased the L-type calcium current (I(Ca(L))) but had no effect on the T-type calcium current (I(Ca(T))), the delayed outward potassium current, or the fast sodium current. This effect of the autoantibody was prevented by a prestimulation of the receptors with methoxamine and vice versa. Moreover, treating the cells with prazosin, a selective alpha1-adrenergic receptor antagonist blocked the methoxamine and the autoantibody-induced increase in I(Ca(L)), respectively. In absence of prazosin, both methoxamine and the autoantibody showed a substantial enhancement in the frequency of cell contraction and that of the concomitant cytosolic and nuclear free Ca2+ variations. The subsequent addition of nifedipine, a specific L-type Ca2+ channel blocker, reversed not only the methoxamine or the autoantibody-induced effect but also completely abolished cell contraction. These results demonstrated that functional alpha1-adrenoceptors exist in both 10-day-old embryonic chick and 20-week-old human fetal hearts and that the autoantibody directed against the second extracellular loop of this type of receptors plays an important role in stimulating their activity via activation of L-type calcium channels. This loop seems to have a functional significance by being the target of alpha1-receptor agonists like methoxamine.

Effects of Neuromodulation on Excitatory-Inhibitory Neural Network Dynamics Depend on Network Connectivity Structure

NASA Astrophysics Data System (ADS)

Rich, Scott; Zochowski, Michal; Booth, Victoria

2018-01-01

Acetylcholine (ACh), one of the brain's most potent neuromodulators, can affect intrinsic neuron properties through blockade of an M-type potassium current. The effect of ACh on excitatory and inhibitory cells with this potassium channel modulates their membrane excitability, which in turn affects their tendency to synchronize in networks. Here, we study the resulting changes in dynamics in networks with inter-connected excitatory and inhibitory populations (E-I networks), which are ubiquitous in the brain. Utilizing biophysical models of E-I networks, we analyze how the network connectivity structure in terms of synaptic connectivity alters the influence of ACh on the generation of synchronous excitatory bursting. We investigate networks containing all combinations of excitatory and inhibitory cells with high (Type I properties) or low (Type II properties) modulatory tone. To vary network connectivity structure, we focus on the effects of the strengths of inter-connections between excitatory and inhibitory cells (E-I synapses and I-E synapses), and the strengths of intra-connections among excitatory cells (E-E synapses) and among inhibitory cells (I-I synapses). We show that the presence of ACh may or may not affect the generation of network synchrony depending on the network connectivity. Specifically, strong network inter-connectivity induces synchronous excitatory bursting regardless of the cellular propensity for synchronization, which aligns with predictions of the PING model. However, when a network's intra-connectivity dominates its inter-connectivity, the propensity for synchrony of either inhibitory or excitatory cells can determine the generation of network-wide bursting.

Inhibition of Kv7/M Channel Currents by the Local Anesthetic Chloroprocaine.

PubMed

Zhang, Fan; Cheng, Yanxin; Li, Hong; Jia, Qingzhong; Zhang, Hailin; Zhao, Senming

2015-01-01

Chloroprocaine is a local ester anesthetic, producing excellent sensory block in clinical use. The Kv7/M potassium channel plays an important role in the control of neuronal excitability. In this study, we investigated the effects of the local anesthetic chloroprocaine on Kv7/M channels as well as the effect of retigabine on chloroprocaine-induced seizures. A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from rat dorsal root ganglion (DRG) neurons. Chloroprocaine produced a number of effects on Kv7.2/Kv7.3 currents, including a lowering of current amplitudes, a rightward shift in the voltage-dependent activation curves, and a slowing of channel activation. Chloroprocaine had a more selective inhibitory effect on the homomeric Kv7.3 and heteromeric Kv7.2/Kv7.3 channels than on the homomeric Kv7.2 channel. Chloroprocaine also inhibited native M channel currents and induced a depolarization of the DRG neuron membrane potential. Taken together, the findings indicate that chloroprocaine concentration dependently inhibited Kv7/M channel currents. © 2015 S. Karger AG, Basel.

Potassium Channels in Peripheral Pain Pathways: Expression, Function and Therapeutic Potential

PubMed Central

Du, Xiaona; Gamper, Nikita

2013-01-01

Electrical excitation of peripheral somatosensory nerves is a first step in generation of most pain signals in mammalian nervous system. Such excitation is controlled by an intricate set of ion channels that are coordinated to produce a degree of excitation that is proportional to the strength of the external stimulation. However, in many disease states this coordination is disrupted resulting in deregulated peripheral excitability which, in turn, may underpin pathological pain states (i.e. migraine, neuralgia, neuropathic and inflammatory pains). One of the major groups of ion channels that are essential for controlling neuronal excitability is potassium channel family and, hereby, the focus of this review is on the K+ channels in peripheral pain pathways. The aim of the review is threefold. First, we will discuss current evidence for the expression and functional role of various K+ channels in peripheral nociceptive fibres. Second, we will consider a hypothesis suggesting that reduced functional activity of K+ channels within peripheral nociceptive pathways is a general feature of many types of pain. Third, we will evaluate the perspectives of pharmacological enhancement of K+ channels in nociceptive pathways as a strategy for new analgesic drug design. PMID:24396338

Modulation by clamping: Kv4 and KChIP interactions.

PubMed

Wang, Kewei

2008-10-01

The rapidly inactivating (A-type) potassium channels regulate membrane excitability that defines the fundamental mechanism of neuronal functions such as pain signaling. Cytosolic Kv channel-interacting proteins KChIPs that belong to neuronal calcium sensor (NCS) family of calcium binding EF-hand proteins co-assemble with Kv4 (Shal) alpha subunits to form a native complex that encodes major components of neuronal somatodendritic A-type K+ current, I(SA), in neurons and transient outward current, I(TO), in cardiac myocytes. The specific binding of auxiliary KChIPs to the Kv4 N-terminus results in modulation of gating properties, surface expression and subunit assembly of Kv4 channels. Here, I attempt to emphasize the interaction between KChIPs and Kv4 based on recent progress made in understanding the structure complex in which a single KChIP1 molecule laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner. Greater insights into molecular mechanism between KChIPs and Kv4 interaction may provide therapeutic potentials of designing compounds aimed at disrupting the protein-protein interaction for treatment of membrane excitability-related disorders.

Incorporating Born solvation energy into the three-dimensional Poisson-Nernst-Planck model to study ion selectivity in KcsA K+ channels

NASA Astrophysics Data System (ADS)

Liu, Xuejiao; Lu, Benzhuo

2017-12-01

Potassium channels are much more permeable to potassium than sodium ions, although potassium ions are larger and both carry the same positive charge. This puzzle cannot be solved based on the traditional Poisson-Nernst-Planck (PNP) theory of electrodiffusion because the PNP model treats all ions as point charges, does not incorporate ion size information, and therefore cannot discriminate potassium from sodium ions. The PNP model can qualitatively capture some macroscopic properties of certain channel systems such as current-voltage characteristics, conductance rectification, and inverse membrane potential. However, the traditional PNP model is a continuum mean-field model and has no or underestimates the discrete ion effects, in particular the ion solvation or self-energy (which can be described by Born model). It is known that the dehydration effect (closely related to ion size) is crucial to selective permeation in potassium channels. Therefore, we incorporated Born solvation energy into the PNP model to account for ion hydration and dehydration effects when passing through inhomogeneous dielectric channel environments. A variational approach was adopted to derive a Born-energy-modified PNP (BPNP) model. The model was applied to study a cylindrical nanopore and a realistic KcsA channel, and three-dimensional finite element simulations were performed. The BPNP model can distinguish different ion species by ion radius and predict selectivity for K+ over Na+ in KcsA channels. Furthermore, ion current rectification in the KcsA channel was observed by both the PNP and BPNP models. The I -V curve of the BPNP model for the KcsA channel indicated an inward rectifier effect for K+ (rectification ratio of ˜3 /2 ) but indicated an outward rectifier effect for Na+ (rectification ratio of ˜1 /6 ) .

Cleistanthus collinus induces type I distal renal tubular acidosis and type II respiratory failure in rats.

PubMed

Maneksh, Delinda; Sidharthan, Anita; Kettimuthu, Kavithapriya; Kanthakumar, Praghalathan; Lourthuraj, Amala A; Ramachandran, Anup; Subramani, Sathya

2010-06-01

A water decoction of the poisonous shrub Cleistanthus collinus is used for suicidal purposes. The mortality rate is 28%. The clinical profile includes distal renal tubular acidosis (DRTA) and respiratory failure. The mechanism of toxicity is unclear. To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s) of action. Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram and respiratory movements were recorded. Either aqueous extract of C. collinus or control solution was administered intraperitoneally. Serial measurements of blood gases, electrolytes and urinary pH were made. Isolated brush border and basolateral membranes from rat kidney were incubated with C. collinus extract and reduction in ATPase activity was assessed. Venous blood samples from human volunteers and rats were incubated with an acetone extract of C. collinus and plasma potassium was estimated as an assay for sodium-potassium pump activity. The mortality was 100% in tests and 17% in controls. Terminal event in test animals was respiratory arrest. Controls had metabolic acidosis, respiratory compensation acidic urine and hyperkalemia. Test animals showed respiratory acidosis, alkaline urine and low blood potassium as compared to controls. C. collinus extract inhibited ATPase activity in rat kidney. Plasma K(+) did not increase in human blood incubated with C. collinus extract. Active principles of C. collinus inhibit proton pumps in the renal brush border, resulting in type I DRTA in rats. There is no inhibition of sodium-potassium pump activity. Test animals develop respiratory acidosis, and the immediate cause of death is respiratory arrest.

Magnetically Activated Self-Cleaning Membranes

DTIC Science & Technology

2010-06-01

potassium phthalimide was reacted with the brushes to attach the phthalimide group to the end of the brushes. Hydralization then yields a primary amine...Synthesis reaction For the first step of the Gabriel Synthesis, 1 g potassium phthalimide was dissolved into 20 mL of ethanol. This solution (4.5 mL...resulting polyacrylic acid (pAA) brushes 12 through an amide linkage. Grafting of pAA brushes was confirmed using two types of spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lolicato, Marco; Arrigoni, Cristina; Mori, Takahiro

Polymodal thermo- and mechanosensitive two-pore domain potassium (K2P) channels of the TREK1 subfamily generate ‘leak’ currents that regulate neuronal excitability, respond to lipids, temperature and mechanical stretch, and influence pain, temperature perception and anaesthetic responses1, 2, 3. These dimeric voltage-gated ion channel (VGIC) superfamily members have a unique topology comprising two pore-forming regions per subunit4, 5, 6. In contrast to other potassium channels, K2P channels use a selectivity filter ‘C-type’ gate7, 8, 9, 10 as the principal gating site. Despite recent advances3, 11, 12, poor pharmacological profiles of K2P channels limit mechanistic and biological studies. Here we describe a classmore » of small-molecule TREK activators that directly stimulate the C-type gate by acting as molecular wedges that restrict interdomain interface movement behind the selectivity filter. Structures of K2P2.1 (also known as TREK-1) alone and with two selective K2P2.1 (TREK-1) and K2P10.1 (TREK-2) activators—an N-aryl-sulfonamide, ML335, and a thiophene-carboxamide, ML402—define a cryptic binding pocket unlike other ion channel small-molecule binding sites and, together with functional studies, identify a cation–π interaction that controls selectivity. Together, our data reveal a druggable K2P site that stabilizes the C-type gate ‘leak mode’ and provide direct evidence for K2P selectivity filter gating.« less

Basolateral K+ channel involvement in forskolin-activated chloride secretion in human colon

PubMed Central

McNamara, Brian; Winter, Desmond C; Cuffe, John E; O'Sullivan, Gerald C; Harvey, Brian J

1999-01-01

In this study we investigated the role of basolateral potassium transport in maintaining cAMP-activated chloride secretion in human colonic epithelium. Ion transport was quantified in isolated human colonic epithelium using the short-circuit current technique. Basolateral potassium transport was studied using nystatin permeabilization. Intracellular calcium measurements were obtained from isolated human colonic crypts using fura-2 spectrofluorescence imaging. In intact isolated colonic strips, forskolin and prostaglandin E2 (PGE2) activated an inward transmembrane current (ISC) consistent with anion secretion (for forskolin ΔISC = 63.8 ± 6.2 μA cm−2, n = 6; for PGE2 ΔISC = 34.3 ± 5.2 μA cm−2, n = 6). This current was inhibited in chloride-free Krebs solution or by inhibiting basolateral chloride uptake with bumetanide and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS). The forskolin- and PGE2-induced chloride secretion was inhibited by basolateral exposure to barium (5 mM), tetrapentylammonium (10 μM) and tetraethylammonium (10 mM). The transepithelial current produced under an apical to serosal K+ gradient in nystatin-perforated colon is generated at the basolateral membrane by K+ transport. Forskolin failed to activate this current under conditions of high or low calcium and failed to increase the levels of intracellular calcium in isolated crypts In conclusion, we propose that potassium recycling through basolateral K+ channels is essential for cAMP-activated chloride secretion. PMID:10432355

Potassium recycling pathways in the human cochlea.

PubMed

Weber, P C; Cunningham, C D; Schulte, B A

2001-07-01

Potential pathways for recycling potassium (K+) used in the maintenance of inner ear electrochemical gradients have been elucidated in animal models. However, little is known about K+ transport in the human cochlea. This study was designed to characterize putative K+ recycling pathways in the human ear and to determine whether observations from animal models can be extrapolated to humans. A prospective laboratory study using an immunohistochemical approach to analyze the distribution of key ion transport mediators in the human cochlea. Human temporal bones were fixed in situ within 1 to 6 hours of death and subsequently harvested at autopsy. Decalcification was accomplished with the aid of microwaving. Immunohistochemical staining was then performed to define the presence and cell type-specific distribution of Na,K-ATPase, sodium-potassium-chloride cotransporter (NKCC), and carbonic anhydrase (CA) in the inner ear. Staining patterns visualized in the human cochlea closely paralleled those seen in other species. Anti-Na,K-ATPase stained strongly the basolateral plasma membrane of strial marginal cells and nerve endings underlying hair cells. This antibody also localized Na,K-ATPase to type II, type IV, and type V fibrocytes in the spiral ligament and in limbal fibrocytes. NKCC was present in the basolateral membrane of strial marginal cells as well as in type II, type V, and limbal fibrocytes. Immunoreactive carbonic anhydrase was present in type I and type III fibrocytes and in epithelial cells lining Reissner's membrane and the spiral prominence. The distribution of several major ion transport proteins in the human cochlea is similar but not identical to that described in various rodent models. These results support the presence of a complex system for recycling and regulating K+ homeostasis in the human cochlea, similar to that described in other mammalian species.

Single Nisoldipine-Sensitive Calcium Channels in Smooth Muscle Cells Isolated from Rabbit Mesenteric Artery

NASA Astrophysics Data System (ADS)

Worley, Jennings F.; Deitmer, Joachim W.; Nelson, Mark T.

1986-08-01

Single smooth muscle cells were enzymatically isolated from the rabbit mesenteric artery. At physiological levels of external Ca, these cells were relaxed and contracted on exposure to norepinephrine, caffeine, or high levels of potassium. The patch-clamp technique was used to measure unitary currents through single channels in the isolated cells. Single channels were selective for divalent cations and exhibited two conductance levels, 8 pS and 15 pS. Both types of channels were voltage-dependent, and channel activity occurred at potentials positive to -40 mV. The activity of both channel types was almost completely inhibited by 50 nM nisoldipine. These channels appear to be the pathways for voltage-dependent Ca influx in vascular smooth muscle and may be the targets of the clinically used dihydropyridines.

The physostigmine depolarization potentiating effect of salicylate in frog skeletal muscle.

PubMed

Varga, E; Kovács, L; Szücs, G; Illés, B

1975-01-01

1) The frog's sartorius muscle was depolarized depending on the degree of concentration 2--4 times more intensely by physostigmine salicylate than by physostigmine sulphate. 2) In normal Ringer's solution, 1 mM physostigmine salicylate decreased the sensitivity of the membrane to potassium depolarization by about 90%. Under similar experimental conditions, physostigmine sulphate and Na salicylate, respectively, decrease the sensitivity of the membrane to potassium depolarization by about 30%. 3) The difference manifested in the depolarizing effect of salicylate and other physostigmine salts (chloride, sulphate, phosphate, formiate, acetate, monochloracetate, benzoate and para-oxy-benzoate) is expressed already at 1 mM concentration (about 10-fold), if the muscle had been equilibrated in chloride-free glucuronate or sulphate milieu. 4) The depolarization develops slowly. It takes 30--60 minutes for the new steady state to develop even in the superficial sartorius fibres. If depolarization has reached its maximum on an average 100 mV, the membrane potential remains unchanged for hours. 5) Depolarization ensues at an unchanged degree in the presence of Na-free (choline) Ringer as well as in the presence of 2X10(-8) g/ml tetrodotoxin; therefore, it is not a Na-dependent process. 6) Under the influence of 1 mM physostigmine salicylate the membrane's resistance to the inward potassium current increased about twofold, while the increase was only 15% to the outward potassium current. It is assumed that the salicylate anion is characteristically capable of potentiating the decreasing effect of physostigmine on potassium permeability, though the role of the metabolic effect of salicylate cannot be excluded.

Big Potassium (BK) ion channels in biology, disease and possible targets for cancer immunotherapy

PubMed Central

Ge, Lisheng; Hoa, Neil T.; Wilson, Zechariah; Arismendi-Morillo, Gabriel; Kong, Xia-Tang; Tajhya, Rajeev B.; Beeton, Christine; Jadus, Martin R.

2017-01-01

The Big Potassium (BK) ion channel is commonly known by a variety of names (Maxi-K, KCNMA1, slo, Stretch-activated potassium channels, KCa1.1). Each name reflects a different physical property displayed by this single ion channel. This transmembrane channel is found on nearly every cell type of the body and has its own distinctive roles for that tissue type. The BKα channel contains the pore that releases potassium ions from intracellular stores. This ion channel is found on the cell membrane, endoplasmic reticulum, Golgi and mitochondria. Complex splicing pathways produce different isoforms. The BKα channels can be phosphorylated, palmitoylated and myristylated. BK is composed of a homo-tetramer that interacts with β and γ chains. These accessory proteins provide a further modulating effect on the functions of BKα channels. BK channels play important roles in cell division and migration. In this review, we will focus on the biology of BK channels, especially its role, and that it has in the immune response towards cancer. Recent proteomic studies have linked BK channels with various proteins. Some of these interactions offer further insight into the role that BK channels have with cancers, especially with brain tumors. This review shows that BK channels have a complex interplay with intracellular components of cancer cells and still have plenty of secrets to be discovered. PMID:25027630

Impact of the post fire management in some soil chemical properties. First results.

NASA Astrophysics Data System (ADS)

Francos, Marcos; Pereira, Paulo; Alcañiz, Meritxell; Úbeda, Xavi

2016-04-01

Post-fire management after severe wildfires has impact on soil properties. In Mediterranean environments management of fire affected areas is a common practice. This intervention may change soil chemical properties of the soil such as major cations. The aim of this work is to study the impact of different types of forest management in soil extractable calcium, magnesium, sodium and potassium after a severe wildfire. The study area is located in Ódena (Catalonia, Spain). The wildfire occurred at July 27th of 2015 and burned 1235 ha. After the fire an experimental plot was designed 9 plots with 2x2 meters (4 square meters). The different managements were: a) clear-cuted area and wood removed, b) no treatment); and c) clear-cutted. The results of the first sampling showed significant differences among all treatments in extractable calcium, sodium and potassium. The amount of these extractable elements was high in clear-cutted treatment in comparison to the others. No differences were identified in extractable magnesium. Overall, in the immediate period after the fire, burned area management, changed the studied soil properties. We are currently studying the evolution of this soil properties in these plots with the time

Electrical Transport Ability of Nanostructured Potassium-Doped Titanium Oxide Film

NASA Astrophysics Data System (ADS)

Lee, So-Yoon; Matsuno, Ryosuke; Ishihara, Kazuhiko; Takai, Madoka

2011-02-01

Potassium-doped nanostructured titanium oxide films were fabricated using a wet corrosion process with various KOH solutions. The doped condition of potassium in TiO2 was confirmed by Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). Nanotubular were synthesized at a dopant concentration of <0.27% when the dopant concentration increased to >0.27%, these structures disappeared. To investigate the electrical properties of K-doped TiO2, pseudo metal-oxide-semiconductor field-effect transistor (MOSFET) samples were fabricated. The samples exhibited a distinct electrical behavior and p-type characteristics. The electrical behavior was governed by the volume of the dopant when the dopant concentration was <0.10% and the volume of the TiO2 phase when the dopant concentration was >0.18%.

Systemic administration of anti-NGF increases A-type potassium currents and decreases pancreatic nociceptor excitability in a rat model of chronic pancreatitis.

PubMed

Zhu, Yaohui; Mehta, Kshama; Li, Cuiping; Xu, Guang-Yin; Liu, Liansheng; Colak, Tugba; Shenoy, Mohan; Pasricha, Pankaj Jay

2012-01-01

We have previously shown that pancreatic sensory neurons in rats with chronic pancreatitis (CP) display increased excitability associated with a decrease in transient inactivating potassium currents (I(A)), thus accounting in part for the hyperalgesia associated with this condition. Because of its well known role in somatic hyperalgesia, we hypothesized a role for the nerve growth factor (NGF) in driving these changes. CP was induced by intraductal injection of trinitrobenzene sulfonic acid (TNBS) in rats. After 3 wk, anti-NGF antibody or control serum was injected intra-peritoneally daily for 1 wk. This protocol was repeated in another set of experiments in control rats (receiving intraductal PBS instead of TNBS). Pancreatic nociceptors labeled with the dye Dil were identified, and patch-clamp recordings were made from acutely dissociated DRG neurons. Sensory neurons from anti-NGF-treated rats displayed a lower resting membrane potential, increased rheobase, decreased burst discharges in response to stimulatory current, and decreased input resistance compared with those treated with control serum. Under voltage-clamp condition, neuronal I(A) density was increased in anti-NGF-treated rats compared with rats treated with control serum. However, anti-NGF treatment had no effect on electrophysiological parameters in neurons from control rats. The expression of Kv-associated channel or ancillary genes Kv1.4, 4.1, 4.2, 4.3, and DPP6, DPP10, and KCHIPs 1-4 in pancreas-specific nociceptors was examined by laser-capture microdissection and real-time PCR quantification of mRNA levels. No significant differences were seen among those. These findings emphasize a key role for NGF in maintaining neuronal excitability in CP specifically via downregulation of I(A) by as yet unknown mechanisms.

Cardiac Delayed Rectifier Potassium Channels in Health and Disease.

PubMed

Chen, Lei; Sampson, Kevin J; Kass, Robert S

2016-06-01

Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization. These include IKs, IKr and the atrial specific IKur channels. In this article, we will review their molecular identities and biophysical properties. Mutations in the genes encoding delayed rectifiers lead to loss- or gain-of-function phenotypes, disrupt normal cardiac repolarization and result in various cardiac rhythm disorders, including congenital Long QT Syndrome, Short QT Syndrome and familial atrial fibrillation. We will also discuss the prospect of using delayed rectifier channels as therapeutic targets to manage cardiac arrhythmia. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiac Delayed Rectifier Potassium Channels in Health and Disease

PubMed Central

Chen, Lei; Sampson, Kevin J.; Kass, Robert S.

2016-01-01

Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization. These include IKs, IKr and the atrial specific IKur channels. In this chapter, we will review the molecular identities and biophysical properties of these channels. Mutations in the genes encoding delayed rectifiers lead to loss- or gain-of-function phenotypes, disrupt normal cardiac repolarization and result in various cardiac rhythm disorders, including congenital Long QT Syndrome, Short QT Syndrome and familial atrial fibrillation. We will also discuss the possibility and prospect of using delayed rectifier channels as therapeutic targets to manage cardiac arrhythmia. PMID:27261823

Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium channel.

PubMed

Leicher, T; Bähring, R; Isbrandt, D; Pongs, O

1998-12-25

Shaker-related voltage-gated potassium (Kv) channels may be heterooligomers consisting of membrane-integral alpha-subunits associated with auxiliary cytoplasmic beta-subunits. In this study we have cloned the human Kvbeta3.1 subunit and the corresponding KCNA3B gene. Identification of sequence-tagged sites in the gene mapped KCNA3B to band p13.1 of human chromosome 17. Comparison of the KCNA1B, KCNA2B, and KCNA3B gene structures showed that the three Kvbeta genes have very disparate lengths varying from >/=350 kb (KCNA1B) to approximately 7 kb (KCNA3B). Yet, the exon patterns of the three genes, which code for the seven known mammalian Kvbeta subunits, are very similar. The Kvbeta1 and Kvbeta2 splice variants are generated by alternative use of 5'-exons. Mouse Kvbeta4, a potential splice variant of Kvbeta3, is a read-through product where the open reading frame starts within the sequence intervening between Kvbeta3 exons 7 and 8. The human KCNA3B sequence does not contain a mouse Kvbeta4-like open reading frame. Human Kvbeta3 mRNA is specifically expressed in the brain, where it is predominantly detected in the cerebellum. The heterologous coexpression of human Kv1.5 and Kvbeta3.1 subunits in Chinese hamster ovary cells yielded a novel Kv channel mediating very fast inactivating (A-type) outward currents upon depolarization. Thus, the expression of Kvbeta3.1 subunits potentially extends the possibilities to express diverse A-type Kv channels in the human brain.

Testosterone-mediated upregulation of delayed rectifier potassium channel in cardiomyocytes causes abbreviation of QT intervals in rats.

PubMed

Masuda, Kimiko; Takanari, Hiroki; Morishima, Masaki; Ma, FangFang; Wang, Yan; Takahashi, Naohiko; Ono, Katsushige

2018-01-13

Men have shorter rate-corrected QT intervals (QTc) than women, especially at the period of adolescence or later. The aim of this study was to elucidate the long-term effects of testosterone on cardiac excitability parameters including electrocardiogram (ECG) and potassium channel current. Testosterone shortened QT intervals in ECG in castrated male rats, not immediately after, but on day 2 or later. Expression of Kv7.1 (KCNQ1) mRNA was significantly upregulated by testosterone in cardiomyocytes of male and female rats. Short-term application of testosterone was without effect on delayed rectifier potassium channel current (I Ks ), whereas I Ks was significantly increased in cardiomyocytes treated with dihydrotestosterone for 24 h, which was mimicked by isoproterenol (24 h). Gene-selective inhibitors of a transcription factor SP1, mithramycin, abolished the effects of testosterone on Kv7.1. Testosterone increases Kv7.1-I Ks possibly through a pathway related to a transcription factor SP1, suggesting a genomic effect of testosterone as an active factor for cardiac excitability.

Non-destructive Measurement of Calcium and Potassium in Apple and Pear Using Handheld X-ray Fluorescence

PubMed Central

Kalcsits, Lee A.

2016-01-01

Calcium and potassium are essential for cell signaling, ion homeostasis and cell wall strength in plants. Unlike nutrients such as nitrogen and potassium, calcium is immobile in plants. Localized calcium deficiencies result in agricultural losses; particularly for fleshy horticultural crops in which elemental imbalances in fruit contribute to the development of physiological disorders such as bitter pit in apple and cork spot in pear. Currently, elemental analysis of plant tissue is destructive, time consuming and costly. This is a limitation for nutrition studies related to calcium in plants. Handheld portable x-ray fluorescence (XRF) can be used to non-destructively measure elemental concentrations. The main objective was to test if handheld XRF can be used for semi-quantitative calcium and potassium analysis of in-tact apple and pear. Semi-quantitative measurements for individual fruit were compared to results obtained from traditional lab analysis. Here, we observed significant correlations between handheld XRF measurements of calcium and potassium and concentrations determined using MP-AES lab analysis. Pearson correlation coefficients ranged from 0.73 and 0.97. Furthermore, measuring apple and pear using handheld XRF identified spatial variability in calcium and potassium concentrations on the surface of individual fruit. This variability may contribute to the development of localized nutritional imbalances. This highlights the importance of understanding spatial and temporal variability in elemental concentrations in plant tissue. Handheld XRF is a relatively high-throughput approach for measuring calcium and potassium in plant tissue. It can be used in conjunction with traditional lab analysis to better understand spatial and temporal patterns in calcium and potassium uptake and distribution within an organ, plant or across the landscape. PMID:27092160

Augmented sodium currents contribute to the enhanced excitability of small diameter capsaicin-sensitive sensory neurons isolated from Nf1+/⁻ mice.

PubMed

Wang, Yue; Duan, J-H; Hingtgen, C M; Nicol, G D

2010-04-01

Neurofibromin, the product of the Nf1 gene, is a guanosine triphosphatase activating protein (GAP) for p21ras (Ras) that accelerates conversion of active Ras-GTP to inactive Ras-GDP. Sensory neurons with reduced levels of neurofibromin likely have augmented Ras-GTP activity. We reported previously that sensory neurons isolated from a mouse model with a heterozygous mutation of the Nf1 gene (Nf1+/⁻) exhibited greater excitability compared with wild-type mice. To determine the mechanism giving rise to the augmented excitability, differences in specific membrane currents were examined. Consistent with the enhanced excitability of Nf1+/⁻ neurons, peak current densities of both tetrodotoxin-resistant sodium current (TTX-R I(Na)) and TTX-sensitive (TTX-S) I(Na) were significantly larger in Nf1+/⁻ than in wild-type neurons. Although the voltages for half-maximal activation (V(0.5)) were not different, there was a significant depolarizing shift in the V(0.5) for steady-state inactivation of both TTX-R and TTX-S I(Na) in Nf1+/⁻ neurons. In addition, levels of persistent I(Na) were significantly larger in Nf1+/⁻ neurons. Neither delayed rectifier nor A-type potassium currents were altered in Nf1+/⁻ neurons. These results demonstrate that enhanced production of action potentials in Nf1+/⁻ neurons results, in part, from larger current densities and a depolarized voltage dependence of steady-state inactivation for I(Na) that potentially leads to a greater availability of sodium channels at voltages near the firing threshold for the action potential.

Short- and long-term inhibition of cardiac inward-rectifier potassium channel current by an antiarrhythmic drug bepridil.

PubMed

Ma, Fangfang; Takanari, Hiroki; Masuda, Kimiko; Morishima, Masaki; Ono, Katsushige

2016-07-01

Bepridil is an effective antiarrhythmic drug on supraventricular and ventricular arrhythmias, and inhibitor of calmodulin. Recent investigations have been elucidating that bepridil exerts antiarrhythmic effects through its acute and chronic application for patients. The aim of this study was to identify the efficacy and the potential mechanism of bepridil on the inward-rectifier potassium channel in neonatal rat cardiomyocytes in acute- and long-term conditions. Bepridil inhibited inward-rectifier potassium current (I K1) as a short-term effect with IC50 of 17 μM. Bepridil also reduced I K1 of neonatal cardiomyocytes when applied for 24 h in the culture medium with IC50 of 2.7 μM. Both a calmodulin inhibitor (W-7) and an inhibitor of calmodulin-kinase II (KN93) reduced I K1 when applied for 24 h as a long-term effect in the same fashion, suggesting that the long-term application of bepridil inhibits I K1 more potently than that of the short-term application through the inhibition of calmodulin kinase II pathway in cardiomyocytes.

Rivaroxaban modulates electrical and mechanical characteristics of left atrium

PubMed Central

2013-01-01

Background Rivaroxaban reduces stroke in patients with atrial fibrillation (AF). Left atrium (LA) plays a critical role in the pathophysiology of AF. However, the electromechanical effects of rivaroxaban on LA are not clear. Results Conventional microelectrodes and a whole-cell patch-clamp were used to record the action potentials (APs) and ionic currents in rabbit LA preparations and isolated single LA cardiomyocytes before and after the administration of rivaroxaban. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently reduced LA (n = 7) AP durations at 90% repolarization (APD90) from 76 ± 2 to 79 ± 3, 67 ± 4 (P < 0.05, vs. control), 59 ± 5, (P < 0.01, vs. control), and 56 ± 4 ms (P < 0.005, vs. control), respectively. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently increased the LA (n = 7) diastolic tension by 351 ± 69 (P < 0.05, vs. control), 563 ± 136 (P < 0.05, vs. control), 582 ± 119 (P < 0.05, vs. control), and 603 ± 108 mg (P < 0.005, vs. control), respectively, but did not change LA contractility. In the presence of L-NAME (100 μM) and indomethacin (10 μM), additional rivaroxaban (300 nM) treatment did not significantly further increase the LA (n = 7) diastolic tension, but shortened the APD90 from 73 ± 2 to 60 ± 6 ms (P < 0.05, vs. control). Rivaroxaban (100 nM) increased the L-type calcium current and ultra-rapid delayed rectifier potassium current, but did not change the transient outward potassium current in isolated LA cardiomyocytes. Conclusions Rivaroxaban modulates LA electrical and mechanical characteristics with direct ionic current effects. PMID:23497194

Differential patterns of injury to the proximal tubule of renal cortical slices following in vitro exposure to mercuric chloride, potassium dichromate, or hypoxic conditions.

PubMed

Ruegg, C E; Gandolfi, A J; Nagle, R B; Brendel, K

1987-09-15

The innate susceptibility of renal cell types to these agents was investigated using precision-cut rabbit renal cortical slices made perpendicular to the cortical-papillary axis. Slices were incubated in DME/F12 medium containing 10 microM, 100 microM, or 1 mM concentrations of either metal for 12 hr or in Krebs-Hepes buffer gassed with nitrogen (100%) for 0.75 to 5 hr of hypoxic exposure. To simulate postischemic reperfusion, some slices were transferred to vessels gassed with oxygen after an initial hypoxic period. Mercuric chloride (100 microM) exposure resulted in damage to the straight regions of proximal tubules by 12 hr leaving convoluted regions unaffected. Hypoxia (2.25 hr) and potassium dichromate (100 microM for 12 hr) both caused injury to the convoluted proximal tubules without affecting straight proximal tubular regions. Mercury concentrations of 10 microM and 1 mM had no effect or injured all cell types within the slice, respectively. Similar results were observed for hypoxic periods less than 1.5 hr or greater than 3 hr of exposure. Potassium dichromate had no measurable affect at 10 microM, but at 1 mM focal lesions were observed after 4 hr of exposure, and by 12 hr all cell types within the slice were affected. Intracellular potassium content normalized to DNA correlated well, but always preceded the pathological lesions observed. These results demonstrate that injury to specific regions of the proximal tubule by these agents relates to an innate susceptibility of the intoxicated cell type independent of physiologic feedback or blood delivery patterns proposed as mechanisms of selective injury from in vivo studies.

Influence of Substrate, Additives, and Pulse Parameters on Electrodeposition of Gold Nanoparticles from Potassium Dicyanoaurate

NASA Astrophysics Data System (ADS)

Vahdatkhah, Parisa; Sadrnezhaad, Sayed Khatiboleslam

2015-12-01

Gold nanoparticles (AuNPs) of less than 50 nm diameter were electrodeposited from cyanide solution by pulsating electric current on modified copper and indium tin oxide (ITO) films coated on glass. Morphology, size, and composition of the deposited AuNPs were studied by X-ray photoelectron spectroscopy, atomic force microscopy, and field emission scanning electron microscopy. Effects of peak current density, pulse frequency, potassium iodide and cysteine on grain size, and morphology of the AuNPs were determined. Experiments showed that cathode current efficiency increases with the pulse frequency and the iodide ion. Size of the AuNPs increased with the current density. The number of nucleation sites was larger on ITO than on Cu layer; while the average diameter of the crystallites on ITO was smaller than on Cu layer.

The feasibility of meeting the WHO guidelines for sodium and potassium: a cross-national comparison study.

PubMed

Drewnowski, Adam; Rehm, Colin D; Maillot, Matthieu; Mendoza, Alfonso; Monsivais, Pablo

2015-03-20

To determine joint compliance with the WHO sodium-potassium goals in four different countries, using data from nationally representative dietary surveys. Compared to national and international recommendations and guidelines, the world's population consumes too much sodium and inadequate amounts of potassium. The WHO recommends consuming less than 2000 mg sodium (86 mmol) and at least 3510 mg potassium (90 mmol) per person per day. Dietary surveillance data were obtained from the National Health and Nutrition Examination Survey (NHANES 2007-2010) for the USA; the Encuesta Nacional de Salud y Nutrición 2012 for Mexico; the Individual and National Study on Food Consumption (INCA2) for France; and the National Diet and Nutrition Survey (NDNS) for the UK. We estimated the proportion of adults meeting the joint WHO sodium-potassium goals in the USA, the UK, France and Mexico. The upper bounds of joint compliance with the WHO sodium-potassium goals were estimated at 0.3% in the USA, 0.15% in Mexico, 0.5% in France and 0.1% in the UK. Given prevailing food consumption patterns and the current food supply, implementing WHO guidelines will be an enormous challenge for global public health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

BK channels are required for multisensory plasticity in the oculomotor system

PubMed Central

Nelson, Alexandra; Faulstich, Michael; Moghadam, Setareh; Onori, Kimberly; Meredith, Andrea; du Lac, Sascha

2017-01-01

SUMMARY Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually-evoked eye movements rapidly restore oculomotor function in wildtype mice but are profoundly impaired in BK channel null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits. PMID:27989457

Delayed Rectifier and A-Type Potassium Channels Associated with Kv 2.1 and Kv 4.3 Expression in Embryonic Rat Neural Progenitor Cells

PubMed Central

Smith, Dean O.; Rosenheimer, Julie L.; Kalil, Ronald E.

2008-01-01

Background Because of the importance of voltage-activated K+ channels during embryonic development and in cell proliferation, we present here the first description of these channels in E15 rat embryonic neural progenitor cells derived from the subventricular zone (SVZ). Activation, inactivation, and single-channel conductance properties of recorded progenitor cells were compared with those obtained by others when these Kv gene products were expressed in oocytes. Methodology/Principal Findings Neural progenitor cells derived from the subventricular zone of E15 embryonic rats were cultured under conditions that did not promote differentiation. Immunocytochemical and Western blot assays for nestin expression indicated that almost all of the cells available for recording expressed this intermediate filament protein, which is generally accepted as a marker for uncommitted embryonic neural progenitor cells. However, a very small numbers of the cells expressed GFAP, a marker for astrocytes, O4, a marker for immature oligodendrocytes, and βIII-tubulin, a marker for neurons. Using immunocytochemistry and Western blots, we detected consistently the expression of Kv2.1, and 4.3. In whole-cell mode, we recorded two outward currents, a delayed rectifier and an A-type current. Conclusions/Significance We conclude that Kv2.1, and 4.3 are expressed in E15 SVZ neural progenitor cells, and we propose that they may be associated with the delayed-rectifier and the A-type currents, respectively, that we recorded. These results demonstrate the early expression of delayed rectifier and A-type K+ currents and channels in embryonic neural progenitor cells prior to the differentiation of these cells. PMID:18270591

Transcellular ion flow in Escherichia coli B and electrical sizing of bacterias.

PubMed

Zimmermann, U; Schulz, J; Pilwat, G

1973-10-01

Dielectric breakdown of cell membranes and, in response, transcellular ion flows were measured in Escherichia coli B 163 and B 525 using a Coulter counter as the detector with a hydrodynamic jet focusing close to the orifice of the counter. Plotting the relative pulse height for compensated amplification of a certain size of the cells against increasing detector current, a rather sharp bend within the linear function was found, which did not occur when measuring fixed cells or polystyrene latex. The start current for transcellular ion flow causing the change of the slope is different for the potassium-deficient mutant B 525 in comparison with the wild-type B 163, indicating a change in the membrane structure of B 525 by mutation and demonstrating the sensitivity of the method for studying slight changes in membrane structure in general. The theoretical size distributions for two current values in the range of transcellular ion flow were constructed from the true size distribution at low detector currents, assuming an idealized sharp changeover of the bacterial conductivity from zero to one-third of the electrolyte conductivity.

Transcellular Ion Flow in Escherichia coli B and Electrical Sizing of Bacterias

PubMed Central

Zimmermann, U.; Schulz, J.; Pilwat, G.

1973-01-01

Dielectric breakdown of cell membranes and, in response, transcellular ion flows were measured in Escherichia coli B 163 and B 525 using a Coulter counter as the detector with a hydrodynamic jet focusing close to the orifice of the counter. Plotting the relative pulse height for compensated amplification of a certain size of the cells against increasing detector current, a rather sharp bend within the linear function was found, which did not occur when measuring fixed cells or polystyrene latex. The start current for transcellular ion flow causing the change of the slope is different for the potassium-deficient mutant B 525 in comparison with the wild-type B 163, indicating a change in the membrane structure of B 525 by mutation and demonstrating the sensitivity of the method for studying slight changes in membrane structure in general. The theoretical size distributions for two current values in the range of transcellular ion flow were constructed from the true size distribution at low detector currents, assuming an idealized sharp changeover of the bacterial conductivity from zero to one-third of the electrolyte conductivity. PMID:4583964

UCP2- and non-UCP2-mediated electric current in eukaryotic cells exhibits different properties.

PubMed

Wang, Ruihua; MoYung, K C; Zhang, M H; Poon, Karen

2015-12-01

Using live eukaryotic cells, including cancer cells, MCF-7 and HCT-116, normal hepatocytes and red blood cells in anode and potassium ferricyanide in cathode of MFC could generate bio-based electric current. Electrons and protons generated from the metabolic reaction in both cytosol and mitochondria contributing to the leaking would mediate the generation of electric current. Both resveratrol (RVT) and 2,4-dinitrophenol (DNP) used to induce proton leak in mitochondria were found to promote electric current production in all cells except red blood cells without mitochondria. Proton leak might be important for electric current production by bringing the charge balance in cells to enhance the further electron leak. The induced electric current by RVT can be blocked by Genipin, an inhibitor of UCP2-mediated proton leak, while that induced by DNP cannot. RVT could reduce reactive oxygen species (ROS) level in cells better than that of DNP. In addition, RVT increased mitochondrial membrane potential (MMP), while DNP decreased it. Results highly suggested the existence of at least two types of electric current that showed different properties. They included UCP2-mediated and non-UCP2-mediated electric current. UCP2-mediated electric current exhibited higher reactive oxygen species (ROS) reduction effect per unit electric current production than that of non-UCP2-mediated electric current. Higher UCP2-mediated electric current observed in cancer cells might contribute to the mechanism of drug resistence. Correlation could not be established between electric current production with either ROS and MMP without distinguishing the types of electric current.

P/Q-type calcium channels activate neighboring calcium-dependent potassium channels in mouse motor nerve terminals.

PubMed

Protti, D A; Uchitel, O D

1997-08-01

The identity of the voltage-dependent calcium channels (VDCC), which trigger the Ca2+-gated K+ currents (IK(Ca)) in mammalian motor nerve terminals, was investigated by means of perineurial recordings. The effects of Ca2+ chelators with different binding kinetics on the activation of IK(Ca) were also examined. The calcium channel blockers of the P/Q family, omega-agatoxin IVA (omega-Aga-IVA) and funnel-web spider toxin (FTX), have been shown to exert a strong blocking effect on IK(Ca). In contrast, nitrendipine and omega-conotoxin GVIA (omega-CgTx) did not affect the Ca2+-activated K+ currents. The intracellular action of the fast Ca2+ buffers BAPTA and DM-BAPTA prevented the activation of the IK(Ca), while the slow Ca2+ buffer EGTA was ineffective at blocking it. These data indicate that P/Q-type VDCC mediate the Ca2+ influx which activates IK(Ca). The spatial association between Ca2+ and Ca2+-gated K+ channels is discussed, on the basis of the differential effects of the fast and slow Ca2+ chelators.

Maintaining Flatness of a Large Aperture Potassium Bromide Beamsplitter through Mounting and Vibration

NASA Technical Reports Server (NTRS)

Losch, Patricia; Lyons, James, III; Morell, Armando; Heaney, Jim

1998-01-01

The Composite Infrared Spectrometer (CIRS) instrument on the Cassini Mission launched in October of 1997. The CIRS instrument contains a mid-infrared and a far-infrared interferometer and operates at 170 Kelvin. The mid-infrared interferometer is a Michelson- type Fourier transform spectrometer utilizing a 3 inch diameter potassium bromide beamsplitter/compensator pair. The potassium bromide elements were tested to verify effects of cooldown and vibration prior to integration into the instrument. The instrument was then aligned at ambient temperatures, tested cryogenically and re-verified after vibration. The stringent design optical figure requirements for the beamsplitter and compensator included fabrication errors, mounting stresses and vibration load effects. This paper describes the challenges encountered in mounting the elements to minimize distortion and to survive vibration.

Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite.

PubMed

Nair, Bindu; Elmore, Amy R

2003-01-01

Sodium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Potassium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are inorganic salts that function as reducing agents in cosmetic formulations. All except Sodium Metabisulfite also function as hair-waving/straightening agents. In addition, Sodium Sulfite, Potassium Sulfite, Sodium Bisulfite, and Sodium Metabisulfite function as antioxidants. Although Ammonium Sulfite is not in current use, the others are widely used in hair care products. Sulfites that enter mammals via ingestion, inhalation, or injection are metabolized by sulfite oxidase to sulfate. In oral-dose animal toxicity studies, hyperplastic changes in the gastric mucosa were the most common findings at high doses. Ammonium Sulfite aerosol had an acute LC(50) of >400 mg/m(3) in guinea pigs. A single exposure to low concentrations of a Sodium Sulfite fine aerosol produced dose-related changes in the lung capacity parameters of guinea pigs. A 3-day exposure of rats to a Sodium Sulfite fine aerosol produced mild pulmonary edema and irritation of the tracheal epithelium. Severe epithelial changes were observed in dogs exposed for 290 days to 1 mg/m(3) of a Sodium Metabisulfite fine aerosol. These fine aerosols contained fine respirable particle sizes that are not found in cosmetic aerosols or pump sprays. None of the cosmetic product types, however, in which these ingredients are used are aerosolized. Sodium Bisulfite (tested at 38%) and Sodium Metabisulfite (undiluted) were not irritants to rabbits following occlusive exposures. Sodium Metabisulfite (tested at 50%) was irritating to guinea pigs following repeated exposure. In rats, Sodium Sulfite heptahydrate at large doses (up to 3.3 g/kg) produced fetal toxicity but not teratogenicity. Sodium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite were not teratogenic for mice, rats, hamsters, or rabbits at doses up to 160 mg/kg. Generally, Sodium Sulfite, Sodium Metabisulfite, and Potassium Metabisulfite were negative in mutagenicity studies. Sodium Bisulfite produced both positive and negative results. Clinical oral and ocular-exposure studies reported no adverse effects. Sodium Sulfite was not irritating or sensitizing in clinical tests. These ingredients, however, may produce positive reactions in dermatologic patients under patch test. In evaluating the positive genotoxicity data found with Sodium Bisulfite, the equilibrium chemistry of sulfurous acid, sulfur dioxide, bisulfite, sulfite, and metabisulfite was considered. This information, however, suggests that some bisulfite may have been present in genotoxicity tests involving the other ingredients and vice versa. On that basis, the genotoxicity data did not give a clear, consistent picture. In cosmetics, however, the bisulfite form is used at very low concentrations (0.03% to 0.7%) in most products except wave sets. In wave sets, the pH ranges from 8 to 9 where the sulfite form would predominate. Skin penetration would be low due to the highly charged nature of these particles and any sulfite that did penetrate would be converted to sulfate by the enzyme sulfate oxidase. As used in cosmetics, therefore, these ingredients would not present a genotoxicity risk. The Cosmetic Ingredient Review Expert Panel concluded that Sodium Sulfite, Potassium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are safe as used in cosmetic formulations.

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

PubMed

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.

PKA modulation of Kv4.2-encoded A-type potassium channels requires formation of a supramolecular complex.

PubMed

Schrader, Laura A; Anderson, Anne E; Mayne, Amber; Pfaffinger, Paul J; Sweatt, John David

2002-12-01

A-type channels, encoded by the pore-forming alpha-subunits of the Kv4.x family, are particularly important in regulating membrane excitability in the CNS and the heart. Given the key role of modulation of A currents by kinases, we sought to investigate the protein structure-function relationships underlying the regulation of these currents by PKA. We have previously shown the existence of two PKA phosphorylation sites in the Kv4.2 sequence; therefore, we focused this study on the Kv4.2 primary subunit. In the present studies we made the surprising finding that PKA phosphorylation of the Kv4.2 alpha-subunit is necessary but not sufficient for channel modulation; channel modulation by PKA required the presence of an ancillary subunit, the K+ channel interacting protein (KChIP3). Therefore, these findings indicate a surprising complexity to kinase regulation of A currents, in that an interaction of two separate molecular events, alpha-subunit phosphorylation and the association of an ancillary subunit (KChIP3), are necessary for phosphorylation-dependent regulation of Kv4.2-encoded A channels by PKA. Overall, our studies indicate that PKA must of necessity act on a supramolecular complex of pore-forming alpha-subunits plus ancillary subunits to alter channel properties.

Potassium vanadate K0.23V2O5 as anode materials for lithium-ion and potassium-ion batteries

NASA Astrophysics Data System (ADS)

Liu, Cailing; Luo, Shaohua; Huang, Hongbo; Wang, Zhiyuan; Wang, Qing; Zhang, Yahui; Liu, Yanguo; Zhai, Yuchun; Wang, Zhaowen

2018-06-01

A layered potassium vanadate K0.23V2O5 has been successfully prepared by the hydrothermal method and evaluated as an anode material for lithium-ion and potassium-ion batteries. High structural stability is demonstrated by the ex situ X-ray diffraction (XRD) and ex situ scanning electron microscopy (SEM). When used as an anode material for lithium-ion batteries, the K0.23V2O5 exhibits a reversible capacity of 480.4 mAh g-1 at 20 mA g-1 after 100 cycles and 439.7 mAh g-1 at 200 mA g-1 after 300 cycles as well as good cycling stability. Even at a high current density of 800 mA g-1, a high reversible capacity of 202.5 mAh g-1 can be retained, indicating excellent rate performance. Whereas in potassium-ion batteries, it retains a capacity of 121.6 mAh g-1 after 150 cycles at 20 mA g-1 and 97.6 mAh g-1 at 100 mA g-1 after 100 cycles. Such superior electrochemical performance of K0.23V2O5 can be ascribed to the special flower-like morphology and structure. Overall, the results highlight the great potential of K0.23V2O5 as an anode material for both lithium-ion and potassium-ion batteries.

Synergistic action of cyclic adenosine monophosphate- and calcium-mediated chloride secretion in a colonic epithelial cell line.

PubMed Central

Cartwright, C A; McRoberts, J A; Mandel, K G; Dharmsathaphorn, K

1985-01-01

Vasoactive intestinal polypeptide (VIP) and the calcium ionophore A23187 caused dose-dependent changes in the potential difference and the short circuit current (Isc) across confluent T84 cell monolayers mounted in modified Ussing chambers. Both VIP and A23187 stimulated net chloride secretion without altering sodium transport. Net chloride secretion accounted for the increase in Isc. When A23187 was tested in combination with VIP, net chloride secretion was significantly greater than predicted from the calculated sum of their individual responses indicating a synergistic effect. VIP increased cellular cyclic AMP (cAMP) production in a dose-dependent manner, whereas A23187 had no effect on cellular cAMP. We then determined whether VIP and A23187 activated different transport pathways. Earlier studies suggest that VIP activates a basolaterally localized, barium-sensitive potassium channel as well as an apically localized chloride conductance pathway. In this study, stimulation of basolateral membrane potassium efflux by A23187 was documented by preloading the monolayers with 86Rb+. Stimulation of potassium efflux by A23187 was additive to the VIP-stimulated potassium efflux. By itself, 0.3 microM A23187 did not alter transepithelial chloride permeability, and its stimulation of basolateral membrane potassium efflux caused only a relatively small amount of chloride secretion. However, in the presence of an increased transepithelial chloride permeability induced by VIP, the effectiveness of A23187 on chloride secretion was greatly augmented. Our studies suggest that cAMP and calcium each activate basolateral potassium channels, but cAMP also activates an apically localized chloride channel. Synergism results from cooperative interaction of potassium channels and the chloride channel. PMID:2997291

Wild-type NM23-H1, but not its S120 mutants, suppresses desensitization of muscarinic potassium current.

PubMed

Otero, A S; Doyle, M B; Hartsough, M T; Steeg, P S

1999-03-08

NM23 (NDP kinase) modulates the gating of muscarinic K+ channels by agonists through a mechanism distinct from GTP regeneration. To better define the function of NM23 in this pathway and to identify sites in NM23 that are important for its role in muscarinic K+ channel function, we utilized MDA-MB-435 human breast carcinoma cells that express low levels of NM23-H1. M2 muscarinic receptors and GIRK1/GIRK4 channel subunits were co-expressed in cells stably transfected with vector only (control), wild-type NM23-H1, or several NM23-H1 mutants. Lysates from all cell lines tested exhibit comparable nucleoside diphosphate (NDP) kinase activity. Whole cell patch clamp recordings revealed a substantial reduction of the acute desensitization of muscarinic K+ currents in cells overexpressing NM23-H1. The mutants NM23-H1P96S and NM23-H1S44A resembled wild-type NM23-H1 in their ability to reduce desensitization. In contrast, mutants NM23-H1S120G and NM23-H1S120A completely abolished the effect of NM23-H1 on desensitization of muscarinic K+ currents. Furthermore, NM23-H1S120G potentiated acute desensitization, indicating that this mutant retains the ability to interact with the muscarinic pathway, but has properties antithetical to those of the wild-type protein. We conclude that NM23 acts as a suppressor of the processes leading to the desensitization of muscarinic K+ currents, and that Ser-120 is essential for its actions.

Signaling of Pigment-Dispersing Factor (PDF) in the Madeira Cockroach Rhyparobia maderae

PubMed Central

Funk, Nico W.; Giese, Maria; Baz, El-Sayed; Stengl, Monika

2014-01-01

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca2+ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca2+ baseline concentration and frequency of oscillating Ca2+ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca2+ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1–4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca2+ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K+ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K+ and Na+ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance. PMID:25269074

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Manoj K., E-mail: mmanoj.ssi@gmail.com; Hashmi, S. A.

The comparative performance of the solid-state electrical double layer capacitors (EDLCs) based on the multiwalled carbon nanotube (MWCNT) electrodes and poly (vinaylidinefluoride-co-hexafluoropropyline) (PVdF-HFP) based gel polymer electrolytes (GPEs) containing potassium and lithium salts have been studied. The room temperature ionic conductivity of the GPEs have been found to be ∼3.8×10{sup −3} and 5.9×10{sup −3} S cm{sup −1} for lithium and potassium based systems. The performance of EDLC cells studied by impedance spectroscopy, cyclic voltammetry and constant current charge-discharge techniques, indicate that the EDLC with potassium salt containing GPE shows excellent performance almost equivalent to the EDLC with Li-salt-based GPE.

Dietary sodium, potassium, and alcohol: key players in the pathophysiology, prevention, and treatment of human hypertension.

PubMed

Koliaki, Chrysi; Katsilambros, Nicholas

2013-06-01

Western industrialized societies are currently experiencing an epidemic expansion of hypertension (HTN), which extends alarmingly even to children and adolescents. HTN constitutes an independent risk factor for cardiorenal disease and represents an extremely common comorbidity of diabetes and obesity. Numerous randomized clinical trials and meta-analyses have provided robust scientific evidence that reduced dietary salt intake, increased dietary potassium intake, moderation of alcohol consumption, optimal weight maintenance, and the adoption of "heart-friendly" dietary patterns such as the Dietary Approaches to Stop Hypertension or the Mediterranean diet can effectively lower blood pressure. Interestingly, the susceptibility of blood pressure to nutritional interventions is greatly variable among individuals, depending on age, race, genetic background, and comorbidities. The purpose of this review is to provide a comprehensive overview of currently available scientific evidence in the constantly evolving field of diet and HTN, placing particular emphasis on the key role of dietary sodium, dietary potassium, and alcohol intake in the pathophysiology, prevention, and treatment of human hypertension. © 2013 International Life Sciences Institute.

Potassium Channels Mediate Killing by Human Natural Killer Cells

NASA Astrophysics Data System (ADS)

Schlichter, Lyanne; Sidell, Neil; Hagiwara, Susumu

1986-01-01

Human natural killer (NK) cells in peripheral blood spontaneously recognize and kill a wide variety of target cells. It has been suggested that ion channels are involved in the killing process because there is a Ca-dependent stage and because killing by presensitized cytotoxic T lymphocytes, which in many respects resembles NK killing, is associated with changes in K and Na transport in the target cell. However, no direct evidence exists for ion channels in NK cells or in their target cells. Using the whole-cell variation of the patch-clamp technique, we found a voltage-dependent potassium (K+) current in NK cells. The K+ current was reduced in a dose-dependent manner by the K-channel blockers 4-aminopyridine and quinidine and by the traditional Ca-channel blockers verapamil and Cd2+. We tested the effects of ion-channel blockers on killing of two commonly used target cell lines: K562, which is derived from a human myeloid leukemia, and U937, which is derived from a human histiocytic leukemia. Killing of K562 target cells, determined in a standard 51Cr-release assay, was inhibited in a dose-dependent manner by verapamil, quinidine, Cd2+, and 4-aminopyridine at concentrations comparable to those that blocked the K+ current in NK cells. In K562 target cells only a voltage-dependent Na+ current was found and it was blocked by concentrations of tetrodotoxin that had no effect on killing. Killing of U937 target cells was also inhibited by the two ion-channel blockers tested, quinidine and verapamil. In this cell line only a small K+ current was found that was similar to the one in NK cells. We could not find any evidence of a Ca2+ current in target cells or in NK cells; therefore, our results cannot explain the Ca dependence of killing. Our findings show that there are K channels in NK cells and that these channels play a necessary role in the killing process. In contrast, the endogenous channel type in the target cell is probably not a factor in determining target cell sensitivity to natural killing.

Ethanol Effects on Dopaminergic Ventral Tegmental Area Neurons During Block of Ih: Involvement of Barium-Sensitive Potassium Currents

PubMed Central

McDaid, John; McElvain, Maureen A.; Brodie, Mark S.

2008-01-01

The dopaminergic neurons of the ventral tegmental area (DA VTA neurons) are important for the rewarding and reinforcing properties of drugs of abuse, including ethanol. Ethanol increases the firing frequency of DA VTA neurons from rats and mice. Because of a recent report on block of ethanol excitation in mouse DA VTA neurons with ZD7288, a selective blocker of the hyperpolarization-activated cationic current Ih, we examined the effect of ZD7288 on ethanol excitation in DA VTA neurons from C57Bl/6J and DBA/2J mice and Fisher 344 rats. Ethanol (80 mM) caused only increases in firing rate in mouse DA VTA neurons in the absence of ZD7288, but in the presence of ZD7288 (30 μM), ethanol produced a more transient excitation followed by a decrease of firing. This same biphasic phenomenon was observed in DA VTA neurons from rats in the presence of ZD7288 only at very high ethanol concentrations (160–240 mM) but not at lower pharmacologically relevant concentrations. The longer latency ethanol-induced inhibition was not observed in DA VTA neurons from mice or rats in the presence of barium (100 μM), which blocks G protein–linked potassium channels (GIRKs) and other inwardly rectifying potassium channels. Ethanol may have a direct effect to increase an inhibitory potassium conductance, but this effect of ethanol can only decrease the firing rate if Ih is blocked. PMID:18614756

Physiological and molecular characterization of an IRK-type inward rectifier K+ channel in a tumour mast cell line.

PubMed

Wischmeyer, E; Lentes, K U; Karschin, A

1995-04-01

The basophilic leucaemia cell line RBL-2H3 exhibits a robust inwardly rectifying potassium current, IKIR, which is likely to be modulated by G proteins. We examined the physiological and molecular properties of this KIR conductance to define the nature of the underlying channel species. The macroscopic conductance revealed characteristics typical of classical K+ inward rectifiers of the IRK type. Channel gating was rapid, first order (tau approximately 1 ms at -100 mV) and steeply voltage dependent. Both activation potential and slope conductance were dependent on extracellular K+ concentration ([K+]o) and inward rectification persisted in the absence of internal Mg2+. The current was susceptible to a concentration- and voltage-dependent block by extracellular Na+, Cs+ and Ba2+. Initial IKIR whole-cell amplitudes as well as current rundown were dependent on the presence of 1 mM internal ATP. Perfusion of intracellular guanosine 5'-Q-(3-thiotriphosphate) (GTP[gamma S]) suppressed IKIR with an average half-time of decline of approximately 400 s. It was demonstrated that the dominant IRK-type 25 pS conductance channel was indeed suppressed by 100 microM preloaded GTP[gamma S]. Reverse transcriptase-polymerase chain reactions (RT-PCR) with RBL cell poly(A)+ RNA identified a full length K+ inward rectifier with 94% base pair homology to the recently cloned mouse IRK1 channel. It is concluded that RBL cells express a classical voltage-dependent IRK-type K+ inward rectifier RBL-IRK1 which is negatively controlled by G proteins.

Diet, blood pressure, and multicollinearity.

PubMed

Reed, D; McGee, D; Yano, K; Hankin, J

1985-01-01

Recent reports of an inverse association between dietary calcium intake and hypertension stimulated this analysis of the relationship of blood pressure to more than 20 dietary factors among a group of 8000 Japanese men in Hawaii. Reported intakes of potassium, calcium, protein, and milk were all inversely associated with blood pressure levels when examined one at a time while controlling for other risk factors. Alcohol intake was directly associated with blood pressure, and was treated as a confounding variable in the analysis. The association of potassium intake with blood pressure was relatively stronger than the associations for other nutrients, but the intake of potassium was so highly correlated with intakes of calcium, milk, and protein that it was not statistically possible to identify the independent association of potassium and blood pressure. Calcium intake was strongly correlated with milk and potassium intakes, and only calcium from dairy sources was associated with blood pressure. These data thus indicate that several dietary factors are inversely related to blood pressure levels independently of other risk factors such as age, body mass, and alcohol intake. The high degree of intercorrelation (multicollinearity) among these dietary factors, however, indicates that the independent role of any specific nutrient cannot be conclusively separated from the possible effects of other nutrients in this type of study.

The function and molecular identity of inward rectifier channels in vestibular hair cells of the mouse inner ear

PubMed Central

Levin, Michaela E.

2012-01-01

Inner ear hair cells respond to mechanical stimuli with graded receptor potentials. These graded responses are modulated by a host of voltage-dependent currents that flow across the basolateral membrane. Here, we examine the molecular identity and the function of a class of voltage-dependent ion channels that carries the potassium-selective inward rectifier current known as IK1. IK1 has been identified in vestibular hair cells of various species, but its molecular composition and functional contributions remain obscure. We used quantitative RT-PCR to show that the inward rectifier gene, Kir2.1, is highly expressed in mouse utricle between embryonic day 15 and adulthood. We confirmed Kir2.1 protein expression in hair cells by immunolocalization. To examine the molecular composition of IK1, we recorded voltage-dependent currents from type II hair cells in response to 50-ms steps from −124 to −54 in 10-mV increments. Wild-type cells had rapidly activating inward currents with reversal potentials close to the K+ equilibrium potential and a whole-cell conductance of 4.8 ± 1.5 nS (n = 46). In utricle hair cells from Kir2.1-deficient (Kir2.1−/−) mice, IK1 was absent at all stages examined. To identify the functional contribution of Kir2.1, we recorded membrane responses in current-clamp mode. Hair cells from Kir2.1−/− mice had significantly (P < 0.001) more depolarized resting potentials and larger, slower membrane responses than those of wild-type cells. These data suggest that Kir2.1 is required for IK1 in type II utricle hair cells and contributes to hyperpolarized resting potentials and fast, small amplitude receptor potentials in response to current inputs, such as those evoked by hair bundle deflections. PMID:22496522

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

PubMed

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.

Ion conduction in the KcsA potassium channel analyzed with a minimal kinetic model.

PubMed

Mafé, Salvador; Pellicer, Julio

2005-02-01

We use a model by Nelson to study the current-voltage and conductance-concentration curves of bacterial potassium channel KcsA without assuming rapid ion translocation. Ion association to the channel filter is rate controlling at low concentrations, but dissociation and transport in the filter can limit conduction at high concentration for ions other than K+. The absolute values of the effective rate constants are tentative but the relative changes in these constants needed to qualitatively explain the experiments should be of significance.

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

PubMed

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 efferent mechanism for altering hair cell membrane potential and decreasing membrane resistance that should reduce sensitivity to hair bundle displacements.

Heparin-induced hyperkalemia.

PubMed

Thomas, C M; Thomas, J; Smeeton, F; Leatherdale, B A

2008-05-01

An 85-year-old lady with type 2 diabetes mellitus of 32 years duration with peripheral neuropathy was admitted under the vascular surgeons with extensive gangrene of her lower limb. She was on insulin for the last 7 years. Initial investigations showed normal serum electrolytes. She was started on antibiotics and unfractionated heparin, and her electrolytes showed hyperkalemia, which persisted on active treatment. Her short synacthen test showed good response, renin was normal with low aldosterone, urinary pH, sodium, potassium and osmolality was normal. On stopping heparin serum, potassium became normal. On restarting heparin (low molecular weight) during a suspected episode of pulmonary embolism, she developed hyperkalemia and heparin was stopped. Her potassium and aldosterone became normal on discontinuation of heparin. She developed hyperkalemia with both unfractionated and low molecular weight heparin.

Chloride concentration affects Kv channel voltage-gating kinetics: Importance of experimental anion concentrations.

PubMed

Bekar, L K; Loewen, M E; Forsyth, G W; Walz, W

2005-09-30

Chloride concentration has been shown to have a dramatic impact on protein folding and subsequent tertiary conformation [K.D. Collins, Ions from the Hofmeister series and osmolytes: effects on proteins in solution and in the crystallization process, Methods 34 (2004) 300-311; I. Jelesarov, E. Durr, R.M. Thomas, H.R. Bosshard, Salt effects on hydrophobic interaction and charge screening in the folding of a negatively charged peptide to a coiled coil (leucine zipper), Biochemistry 37 (1998) 7539-7550]. As it is known that Kv channel gating is linked to the stability of the cytoplasmic T1 multimerization domain conformation [D.L. Minor, Y.F. Lin, B.C. Mobley, A. Avelar, Y.N. Jan, L.Y. Jan, J.M. Berger, The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel, Cell 102 (2000) 657-670; B.A. Yi, D.L. Minor Jr., Y.F. Lin, Y.N. Jan, L.Y. Jan, Controlling potassium channel activities: interplay between the membrane and intracellular factors, Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 11016-11023] and that intracellular chloride concentration has been linked to Kv channel kinetics [L.K. Bekar, W. Walz, Intracellular chloride modulates A-type potassium currents in astrocytes, Glia 39 (2002) 207-216; W.B. Thoreson, S.L. Stella, Anion modulation of calcium current voltage dependence and amplitude in salamander rods, Biochim. Biophys. Acta 1464 (2000) 142-150], the objective of the present study was to address how chloride concentration changes affect Kv channel kinetics more closely in an isolated expression system. Initially, no significant chloride concentration-dependent effects on channel steady-state gating kinetics were observed. Only after disruption of the cytoskeleton with cytochalasin-D did we see significant chloride concentration-dependent shifts in gating kinetics. This suggests that the shift in gating kinetics is mediated through effects of intracellular chloride concentration on cytoplasmic domain tertiary conformation as cytoskeletal interaction appears to mask the effect. Furthermore, as cytoskeletal disruption only impacts channel gating kinetics at low physiological intracellular chloride concentrations, these studies highlight the importance of paying close attention to anion concentrations used under experimental conditions.

Petrography and petrology of Smoky Butte intrusives, Garfield County, Montana

USGS Publications Warehouse

Matson, Robert E.

1960-01-01

The Smoky Butte intrusives are located in T. 18 N., R. 36 E. Garfield County, Montana on the extreme eastern edge of the petrographic province of Central Montana. They consist of dikes and plugs arranged in linear, en-echelon pattern with a northeast trend and intrude the Tullock member (Paleocene age) of the Fort Union formation. Extrusive rocks are absent. The rocks are potassium-rich volcanic types showing a disequilibrium mineral assemblage consisting of sanidine, leucite, biotite, olivine, pyroxene, magnetite plus. ilmenite, apatite, calcite, quartz, and a yellowish to dark greenish glassy groundmass. Two chemical analyses of Smoky Butte rocks show high magnesium, potassium, titanium, and phosphorous and low aluminum and sodium content. The two norm calculations show that the rocks are oversaturated with 1.3 and 3.1 per-cent excess silica. Because of the peculiar nature of the Smoky Butte rocks, descriptive names have been applied to them. They are divided into six different types. Three periods of intrusion are proposed for Smoky Butte quarry where three rock types crop out. Other evidence for multiple injection occurs in several multiple dikes. The upper contact of the intrusion is visible on a few plugs and dikes. Smoky Butte rocks show some similarities to the undersaturated potassium-rich rocks of the Highwood and Bearpaw Mountains of Montana, the rocks of the Leucite Hills of Wyoming, and the oversaturated rocks of the West Kimberly District of Australia.

Genome-wide linkage and positional candidate gene study of blood pressure response to dietary potassium intervention: the genetic epidemiology network of salt sensitivity study.

PubMed

Kelly, Tanika N; Hixson, James E; Rao, Dabeeru C; Mei, Hao; Rice, Treva K; Jaquish, Cashell E; Shimmin, Lawrence C; Schwander, Karen; Chen, Chung-Shuian; Liu, Depei; Chen, Jichun; Bormans, Concetta; Shukla, Pramila; Farhana, Naveed; Stuart, Colin; Whelton, Paul K; He, Jiang; Gu, Dongfeng

2010-12-01

Genetic determinants of blood pressure (BP) response to potassium, or potassium sensitivity, are largely unknown. We conducted a genome-wide linkage scan and positional candidate gene analysis to identify genetic determinants of potassium sensitivity. A total of 1906 Han Chinese participants took part in a 7-day high-sodium diet followed by a 7-day high-sodium plus potassium dietary intervention. BP measurements were obtained at baseline and after each intervention using a random-zero sphygmomanometer. Significant linkage signals (logarithm of odds [LOD] score, >3) for BP responses to potassium were detected at chromosomal regions 3q24-q26.1, 3q28, and 11q22.3-q24.3. Maximum multipoint LOD scores of 3.09 at 3q25.2 and 3.41 at 11q23.3 were observed for absolute diastolic BP (DBP) and mean arterial pressure (MAP) responses, respectively. Linkage peaks of 3.56 at 3q25.1 and 3.01 at 11q23.3 for percent DBP response and 3.22 at 3q25.2, 3.01 at 3q28, and 4.48 at 11q23.3 for percent MAP response also were identified. Angiotensin II receptor, type 1 (AGTR1), single-nucleotide polymorphism rs16860760 in the 3q24-q26.1 region was significantly associated with absolute and percent systolic BP responses to potassium (P=0.0008 and P=0.0006, respectively). Absolute (95% CI) systolic BP responses for genotypes C/C, C/T, and T/T were -3.71 (-4.02 to -3.40), -2.62 (-3.38 to -1.85), and 1.03 (-3.73 to 5.79) mm Hg, respectively, and percent responses (95% CI) were -3.07 (-3.33 to -2.80), -2.07 (-2.74 to -1.41), and 0.90 (-3.20 to 4.99), respectively. Similar trends were observed for DBP and MAP responses. Genetic regions on chromosomes 3 and 11 may harbor important susceptibility loci for potassium sensitivity. Furthermore, the AGTR1 gene was a significant predictor of BP responses to potassium intake.

A Quantitative Tunneling/Desorption Model for the Exchange Current at the Porous Electrode/Beta - Alumina/Alkali Metal Gas Three Phase Zone at 700-1300K

NASA Technical Reports Server (NTRS)

Williams, R. M.; Ryan, M. A.; Saipetch, C.; LeDuc, H. G.

1996-01-01

The exchange current observed at porous metal electrodes on sodium or potassium beta -alumina solid electrolytes in alkali metal vapor is quantitatively modeled with a multi-step process with good agreement with experimental results.

Physical and functional interaction between integrins and hERG potassium channels.

PubMed

Arcangeli, A; Becchetti, A; Cherubini, A; Crociani, O; Defilippi, P; Guasti, L; Hofmann, G; Pillozzi, S; Olivotto, M; Wanke, E

2004-11-01

Integrins are adhesion receptors capable of transmitting intracellular signals that regulate many different cellular functions. Among integrin-mediated signals, the activation of ion channels can be included. We demonstrated that a long-lasting activation of hERG (human ether-a-go-go-related gene) potassium channels occurs in both human neuroblastoma and leukaemia cells after the activation of the beta1 integrin subunit. This activation is apparently a determining factor inducing neurite extension and osteoclastic differentiation in both the cell types. More recently, we provided evidences that beta1 integrins and hERG channels co-precipitate in both the cell types. Preliminary results suggest that a macromolecular signalling complex indeed occurs between integrins and the hERG1 protein and that hERG channel activity can modulate integrin downstream signalling.

Somatostatinergic modulation of firing pattern and calcium-activated potassium currents in medium spiny neostriatal neurons.

PubMed

Galarraga, E; Vilchis, C; Tkatch, T; Salgado, H; Tecuapetla, F; Perez-Rosello, T; Perez-Garci, E; Hernandez-Echeagaray, E; Surmeier, D J; Bargas, J

2007-05-11

Somatostatin is synthesized and released by aspiny GABAergic interneurons of the neostriatum, some of them identified as low threshold spike generating neurons (LTS-interneurons). These neurons make synaptic contacts with spiny neostriatal projection neurons. However, very few somatostatin actions on projection neurons have been described. The present work reports that somatostatin modulates the Ca(2+) activated K(+) currents (K(Ca) currents) expressed by projection cells. These actions contribute in designing the firing pattern of the spiny projection neuron; which is the output of the neostriatum. Small conductance (SK) and large conductance (BK) K(Ca) currents represent between 30% and 50% of the sustained outward current in spiny cells. Somatostatin reduces SK-type K(+) currents and at the same time enhances BK-type K(+) currents. This dual effect enhances the fast component of the after hyperpolarizing potential while reducing the slow component. Somatostatin then modifies the firing pattern of spiny neurons which changed from a tonic regular pattern to an interrupted "stuttering"-like pattern. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) tissue expression analysis of dorsal striatal somatostatinergic receptors (SSTR) mRNA revealed that all five SSTR mRNAs are present. However, single cell RT-PCR profiling suggests that the most probable receptor in charge of this modulation is the SSTR2 receptor. Interestingly, aspiny interneurons may exhibit a "stuttering"-like firing pattern. Therefore, somatostatin actions appear to be the entrainment of projection neurons to the rhythms generated by some interneurons. Somatostatin is then capable of modifying the processing and output of the neostriatum.

Effect of biochar type on macronutrient retention and release from soilless substrate

USDA-ARS?s Scientific Manuscript database

A series of column studies were conducted to determine the influence of three different biochar types on nitrate, phosphate, and potassium retention and leaching in a typical greenhouse soilless substrate. Glass columns were filled with 85 sphagnum peat moss : 15 perlite (v:v) and amended with 10% ...

The Effects of 4-Hydroxybenzoic Acid Identified from Bamboo (Dendrocalamus asper) Shoots on Kv1.4 Channel

PubMed Central

Mohamad, Fatin H.; Wong, Jia Hui; Mohamad, Habsah; Ismail, Abdul Hadi; Mohamed Yusoff, Abdul Aziz; Osman, Hasnah; Wong, Kok Tong; Idris, Zamzuri; Abdullah, Jafri Malin

2018-01-01

Background Bamboo shoot has been used as a treatment for epilepsy in traditional Chinese medicine for generations to treat neuronal disorders such as convulsive, dizziness and headaches. 4-hydroxybenzoic acid (4-hba) is a non-flavonoid phenol found abundantly in Dendrocalamus asper shoots (bamboo), fruits (strawberries and apples) and flowers. Kv1.4 is a rapidly inactivating Shaker-related member of the voltage-gated potassium channels with two inactivation mechanisms; the fast N-type and slow C-type. It plays vital roles in repolarisation, hyperpolarisation and signaling the restoration of resting membrane potential through the regulation of the movement of K+ across the cellular membrane. Methods Chemical compounds from Dendrocalamus asper bamboo shoots were purified and identified as major palmitic acids mixed with other minor fatty acids, palmitic acid, 4-hydroxybenzaldehyde, lauric acid, 4-hydroxybenzoic acid and cholest-4-ene-3-one. The response of synthetic 4-hydroxybenzoic acid was tested on Kv1.4 potassium channel which was injected into viable oocytes that was extracted from Xenopus laevis. The current were detected by the two-microelectrode voltage clamp, holding potential starting from −80 mV with 20 mV step-up until +80 mV. Readings of treatments with 0.1% DMSO, 4-hba concentrations and K channel blockers were taken at +60 mV. The ratio of tail/peak amplitude is the index of the activity of the Kv1.4 channels with n ≥ 6 (number of oocytes tested). The decreases of the ratios of five different concentrations (1 μM, 10 μM, 100 μM, 1 mM and 2.5 mM) were compared with 0.1% DMSO as the control. Results All concentration showed statistically significant results with P < 0.05 except for 100 μM. The normalised current of the 4-hba concentrations were compared with potassium channel blockers (TEA and 4-AP) and all groups showed statistically significant results. This study also showed that time taken for each concentration to affect Kv1.4 does not play any significant roles. Conclusion 4-hydroxybenzoic acid was found to be able to enhance the inactivation of Kv1.4 by lowering the membrane potential so that the abnormal neuronal firing can be inhibited. With IC50 slightly higher than 10 μM, increasing concentrations (100 μM, 1 mM and 2.5 mM) had shown to exhibit toxicity effects. The best concentration from this study is 10 μM with Hill slope of 0.1799. PMID:29599640

Fumigant Management Plan Templates - Phase 2 Files Listed by Chemical

EPA Pesticide Factsheets

FMP templates are in PDF and Word formats for each type of soil fumigant pesticide, with samples of filled out plans. Types are by active ingredient chemical: Chloropicrin, dazomet, dimethyl disulfide, metam sodium/potassium, and methyl bromide.

Impact of Soil Composition and Electrochemistry on Corrosion of Rock-cut Slope Nets along Railway Lines in China.

PubMed

Chen, Jiao; Chen, Zhaoqiong; Ai, Yingwei; Xiao, Jingyao; Pan, Dandan; Li, Wei; Huang, Zhiyu; Wang, Yumei

2015-10-09

Taking the slope of Suiyu Railway to study, the research separately studied soil resistivity, soil electrochemistry (corrosion potential, oxidization reduction potential, electric potential gradient and pH), soil anions (total soluble salt, Cl(-), SO4(2-) and ), and soil nutrition (moisture content, organic matter, total nitrogen, alkali-hydrolysable nitrogen, available phosphorus, and available potassium) at different slope levels, and conducted corrosion grade evaluation on artificial soil according to its single index and comprehensive indexes. Compared with other factors, water has the biggest impact on the corrosion of slope protection net, followed by anion content. Total soluble salt has the moderate impact on the corrosion of slope protection net, and stray current has the moderate impact on the corrosion of mid-slope protection net. Comprehensive evaluation on the corrosive degree of soil samples indicates that the corrosion of upper slope is moderate, and the corrosion of mid-slope and lower slope is strong. Organic matter in soil is remarkably relevant to electric potential gradient. Available nitrogen, available potassium and available phosphorus are remarkably relevant to anions. The distribution of soil nutrient is indirectly relevant to slope type.

Impact of Soil Composition and Electrochemistry on Corrosion of Rock-cut Slope Nets along Railway Lines in China

PubMed Central

Chen, Jiao; Chen, Zhaoqiong; Ai, Yingwei; Xiao, Jingyao; Pan, Dandan; Li, Wei; Huang, Zhiyu; Wang, Yumei

2015-01-01

Taking the slope of Suiyu Railway to study, the research separately studied soil resistivity, soil electrochemistry (corrosion potential, oxidization reduction potential, electric potential gradient and pH), soil anions (total soluble salt, Cl−, SO42− and ), and soil nutrition (moisture content, organic matter, total nitrogen, alkali-hydrolysable nitrogen, available phosphorus, and available potassium) at different slope levels, and conducted corrosion grade evaluation on artificial soil according to its single index and comprehensive indexes. Compared with other factors, water has the biggest impact on the corrosion of slope protection net, followed by anion content. Total soluble salt has the moderate impact on the corrosion of slope protection net, and stray current has the moderate impact on the corrosion of mid-slope protection net. Comprehensive evaluation on the corrosive degree of soil samples indicates that the corrosion of upper slope is moderate, and the corrosion of mid-slope and lower slope is strong. Organic matter in soil is remarkably relevant to electric potential gradient. Available nitrogen, available potassium and available phosphorus are remarkably relevant to anions. The distribution of soil nutrient is indirectly relevant to slope type. PMID:26450811

SLO-2 potassium channel is an important regulator of neurotransmitter release in Caenorhabditis elegans

PubMed Central

Liu, Ping; Chen, Bojun; Wang, Zhao-Wen

2014-01-01

Slo2 channels are prominent K+ channels in mammalian neurons but their physiological functions are not well understood. Here we investigate physiological functions and regulation of the C. elegans homologue SLO-2 in motor neurons through electrophysiological analyses of wild-type and mutant worms. We find that SLO-2 is the primary K+ channel conducting delayed outward current in cholinergic motor neurons, and one of two K+ channels with this function in GABAergic motor neurons. Loss-of-function mutation of slo-2 increases the duration and charge transfer rate of spontaneous postsynaptic current bursts at the neuromuscular junction, which are physiological signals used by motor neurons to control muscle cells, without altering postsynaptic receptor sensitivity. SLO-2 activity in motor neurons depends on Ca2+ entry through EGL-19, an L-type voltage-gated Ca2+ channel (CaV1), but not on other proteins implicated in either Ca2+ entry or intracellular Ca2+ release. Thus, SLO-2 is functionally coupled with CaV1 and regulates neurotransmitter release. PMID:25300429

Installation Restoration Program, Phase I: Records Search, Laughlin Air Force Base, Texas.

DTIC Science & Technology

1985-03-01

and chemical * cleaning shops and consists of chromic acid, potassium permanganate, cadmium , and descaling solutions. The general trend in waste...0.016 Cadmium ɘ.010 mg/1 ɘ.010 Chromium 0.091 mg/l ɘ.050 Source: LAFB BES, 1984. STP Analysis Results, April 23, 1984. 3-33 -r --r - - - - 41 . N...consists of chromic acid, potassium permanganate, cadmium , and descaling solutions. The fire suppressants currently employed at LAFB and EPAux are AFFF

Performance of microbial fuel cell double chamber using mozzarella cheese whey substrate

NASA Astrophysics Data System (ADS)

Darmawan, M. D.; Hawa, L. C.; Argo, B. D.

2018-03-01

Nowadays the availability of electric energy is decreasing, hence there is a need for innovation of electric energy producer alternative; one of them is microbial fuel cell (MFC). MFC is a bioelectrochemical system generated by bacterial metabolism that utilizes organic substrate. One of the substrates that can be used is whey, a waste generated from cheese production. Therefore, this study aimed to determine the power of potential current and voltage generated from the use of whey cheese as a substrate for bacterial metabolism. In this research, double chamber system was used in microbial fuel cell reactor by using cheese whey as substrate at anode and potassium permanganate as cathode and utilizing membrane nafion 212 as membrane of proton exchange. The variable of experiment was bacteria type. The types of bacteria used in this study were Lactobacillus bulgaricus, Streptococcus thermophillus and Lactobacillus casei. While the operating time used was 100 hours. The highest current produced was 74.6 μA and the highest voltage was 529.3 mV produced by Lactobacillus bulgaricus bacteria. In this study, it was also found that the death phase of the three bacteria was at 70-80 hours.

Renal Tubular Acidosis

MedlinePlus

... is called transport. One researcher has theorized that Charles Dickens may have been describing a child with ... urine and the potassium level in the blood will help identify which type of RTA a person ...

[How do antiepileptic drugs work?].

PubMed

Nakken, Karl O; Heuser, Kjell; Alfstad, Kristin; Taubøll, Erik

2014-01-14

There are currently around 25 antiepileptic drugs in use in Norway, of which 15 have entered the market in the last 20 years. All have somewhat different effect- and adverse effect profiles and mechanisms of action. Here we present a brief overview of current knowledge regarding the basic mechanisms of action of these drugs. The review is based on a discretionary selection of relevant articles found through a literature search in PubMed and our own clinical and research experience. There are, roughly speaking, four main mechanisms; 1) modulation of ion channels (sodium and calcium channel blockers, potassium channel openers), 2) potentiation of GABAergic inhibition, 3) reduction of glutamatergic excitation and 4) modulation of presynaptic neurotransmitter release. Some of the drugs have several mechanisms of action, and for some of them it is unclear which mechanism is clinically most important. To some extent, the drugs' mechanisms of action predict their effect against different types of epilepsy and seizures. For instance, sodium channel blockers work best against focal seizures, while calcium channel blockers work best against absences, a type of generalised seizure. Optimal treatment of patients with epilepsy requires not only thorough knowledge of seizure- and epilepsy classification, but also insight into the mechanisms of action of antiepileptic drugs.

Arrhythmogenic KCNE gene variants: current knowledge and future challenges

PubMed Central

Crump, Shawn M.; Abbott, Geoffrey W.

2014-01-01

There are twenty-five known inherited cardiac arrhythmia susceptibility genes, all of which encode either ion channel pore-forming subunits or proteins that regulate aspects of ion channel biology such as function, trafficking, and localization. The human KCNE gene family comprises five potassium channel regulatory subunits, sequence variants in each of which are associated with cardiac arrhythmias. KCNE gene products exhibit promiscuous partnering and in some cases ubiquitous expression, hampering efforts to unequivocally correlate each gene to specific native potassium currents. Likewise, deducing the molecular etiology of cardiac arrhythmias in individuals harboring rare KCNE gene variants, or more common KCNE polymorphisms, can be challenging. In this review we provide an update on putative arrhythmia-causing KCNE gene variants, and discuss current thinking and future challenges in the study of molecular mechanisms of KCNE-associated cardiac rhythm disturbances. PMID:24478792

Omega-conotoxin- and nifedipine-insensitive voltage-operated calcium channels mediate K(+)-induced release of pro-thyrotropin-releasing hormone-connecting peptides Ps4 and Ps5 from perifused rat hypothalamic slices.

PubMed

Valentijn, K; Tranchand Bunel, D; Vaudry, H

1992-07-01

The rat thyrotropin-releasing hormone (TRH) precursor (prepro-TRH) contains five copies of the TRH progenitor sequence linked together by intervening sequences. Recently, we have shown that the connecting peptides prepro-TRH-(160-169) (Ps4) and prepro-TRH-(178-199) (Ps5) are released from rat hypothalamic neurones in response to elevated potassium concentrations, in a calcium-dependent manner. In the present study, the role of voltage-operated calcium channels in potassium-induced release of Ps4 and Ps5 was investigated, using a perifusion system for rat hypothalamic slices. The release of Ps4 and Ps5 stimulated by potassium (70 mM) was blocked by the inorganic ions Co2+ (2.6 mM) and Ni2+ (5 mM). In contrast, the stimulatory effect of KCl was insensitive to Cd2+ (100 microM). The dihydropyridine antagonist nifedipine (10 microM) had no effect on K(+)-evoked release of Ps4 and Ps5. Furthermore, the response to KCl was not affected by nifedipine (10 microM) in combination with diltiazem (1 microM), a benzothiazepine which increases the affinity of dihydropyridine antagonists for their receptor. The dihydropyridine agonist BAY K 8644, at concentrations as high as 1 mM, did not stimulate the basal secretion of Ps4 and Ps5. In addition, BAY K 8644 had no potentiating effect on K(+)-induced release of Ps4 and Ps5. The marine cone snail toxin omega-conotoxin, a blocker of both L- and N-type calcium channels had no effect on the release of Ps4 and Ps5 stimulated by potassium. Similarly, the omega-conopeptide SNX-111, a selective blocker of N-type calcium channels, did not inhibit the stimulatory effect of potassium. The release of Ps4 and Ps5 evoked by high K+ was insensitive to the non-selective calcium channel blocker verapamil (20 microM). Amiloride (1 microM), a putative blocker of T-type calcium channels, did not affect KCl-induced secretion of the two connecting peptides. Taken together, these results indicate that two connecting peptides derived from the pro-TRH, Ps4 and Ps5, are released by K(+)-induced depolarization through activation of voltage-sensitive calcium channels. The calcium channels appear to have a pharmacological profile different from that of L- and N-type channels. Although, their insensitivity to low Cd2+ concentrations and sensitivity to Ni2+ ions would support the involvement of T-type calcium channels, the lack of effect of amiloride suggests that they belong to a yet undefined class of calcium channels.

Multi-ion detection by one-shot optical sensors using a colour digital photographic camera.

PubMed

Lapresta-Fernández, Alejandro; Capitán-Vallvey, Luis Fermín

2011-10-07

The feasibility and performance of a procedure to evaluate previously developed one-shot optical sensors as single and selective analyte sensors for potassium, magnesium and hardness are presented. The procedure uses a conventional colour digital photographic camera as the detection system for simultaneous multianalyte detection. A 6.0 megapixel camera was used, and the procedure describes how it is possible to quantify potassium, magnesium and hardness simultaneously from the images captured, using multianalyte one-shot sensors based on ionophore-chromoionophore chemistry, employing the colour information computed from a defined region of interest on the sensing membrane. One of the colour channels in the red, green, blue (RGB) colour space is used to build the analytical parameter, the effective degree of protonation (1-α(eff)), in good agreement with the theoretical model. The linearization of the sigmoidal response function increases the limit of detection (LOD) and analytical range in all cases studied. The increases were from 5.4 × 10(-6) to 2.7 × 10(-7) M for potassium, from 1.4 × 10(-4) to 2.0 × 10(-6) M for magnesium and from 1.7 to 2.0 × 10(-2) mg L(-1) of CaCO(3) for hardness. The method's precision was determined in terms of the relative standard deviation (RSD%) which was from 2.4 to 7.6 for potassium, from 6.8 to 7.8 for magnesium and from 4.3 to 7.8 for hardness. The procedure was applied to the simultaneous determination of potassium, magnesium and hardness using multianalyte one-shot sensors in different types of waters and beverages in order to cover the entire application range, statistically validating the results against atomic absorption spectrometry as the reference procedure. Accordingly, this paper is an attempt to demonstrate the possibility of using a conventional digital camera as an analytical device to measure this type of one-shot sensor based on ionophore-chromoionophore chemistry instead of using conventional lab instrumentation.

Cochlear potential difference between endolymph fluid and the hair cell's interior: a retold interpretation based on the Goldman equation.

PubMed

Kurbel, Sven; Borzan, Vladimir; Golem, Hilda; Dinjar, Kristijan

2017-02-01

Reported cochlear potential values of near 150 mV are often attributed to endolymph itself, although membrane potentials result from ion fluxes across the adjacent semipermeable membranes due to concentration gradients. Since any two fluids separated by a semipermeable membrane develop potential due to differences in solute concentrations, a proposed interpretation here is that positive potential emanates from the Reissner membrane due to small influx of sodium from perilymph to endolymph. Basolateral hair cell membranes leak potassium into the interstitial fluid and this negative potential inside hair cells further augments the electric gradient of cochlear potential. Taken together as a sum, these two potentials are near the reported values of cochlear potential. This is based on reported data for cochlear fluids used for the calculation of Nernst and Goldman potentials. The reported positive potential of Reissner membrane can be explained almost entirely by the traffic of Na+ that enters endolymph through this membrane. At the apical membrane of hair cells, acoustic stimulation modulates stereocillia permeability to potassium. Potassium concentration gradients on the apical membrane are low (the calculated Nernst value is <+3 mV), suggesting that the potassium current is not caused by the local potassium concentration gradient, but an electric field between the positive sodium generated potential on the Reissner membrane and negative inside hair cells. Potassium is forced by this overall electric field to enter hair cells when stereocilia are permeable due to mechanical bending. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Analysis of factors causing hyperkalemia.

PubMed

Takaichi, Kenmei; Takemoto, Fumi; Ubara, Yoshifumi; Mori, Yasumichi

2007-01-01

Patients with impaired renal function or diabetes are considered to be prone to hyperkalemia. Furthermore, hyperkalemia is an adverse drug reaction of inhibitors of the renin-angiotensin system (RAS) that are established to be efficacious in these patients. However, the current status of hyperkalemia in the clinical setting remains obscure. A total of 9,117 patients treated at Toranomon Hospital between January and October 2005, who had serum creatinine levels below 5 mg/dL were studied. Patients on dialysis and patients using cation exchange resin or diuretics that lower serum potassium were excluded. Serum potassium increased significantly accompanying the increase in serum creatinine, and was significantly elevated in diabetic patients compared to non-diabetic patients. Serum potassium also increased significantly with the administration of angiotensin-II receptor blockers (ARB), angiotensin-converting-enzyme inhibitors (ACEI) or beta-blockers. A combination of diabetes and RAS inhibitor administration significantly increased serum potassium compared to each factor alone in patients with a serum creatinine level below 1.5 mg/dL but not in those with a higher serum creatinine level. According to step-wise multiple regression analyses, an elevated serum creatinine level had the strongest positive correlation with the serum potassium level, followed by diabetes, ACEI use, ARB use, and age. Lowered renal function, diabetes, use of RAS inhibitors and old age are independent factors that increase the serum potassium level. Caution should be exercised when using RAS inhibitors in diabetic patients even if their renal function is relatively preserved. In selected patients with diabetes or impaired renal function, however, RAS inhibitors can be used without hyperkalemia.

Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets

PubMed Central

Noujaim, Sami F.; Stuckey, Jeanne A.; Ponce-Balbuena, Daniela; Ferrer-Villada, Tania; López-Izquierdo, Angelica; Pandit, Sandeep; Calvo, Conrado J.; Grzeda, Krzysztof R.; Berenfeld, Omer; Sánchez Chapula, José A.; Jalife, José

2010-01-01

Atrial and ventricular tachyarrhythmias can be perpetuated by up-regulation of inward rectifier potassium channels. Thus, it may be beneficial to block inward rectifier channels under conditions in which their function becomes arrhythmogenic (e.g., inherited gain-of-function mutation channelopathies, ischemia, and chronic and vagally mediated atrial fibrillation). We hypothesize that the antimalarial quinoline chloroquine exerts potent antiarrhythmic effects by interacting with the cytoplasmic domains of Kir2.1 (IK1), Kir3.1 (IKACh), or Kir6.2 (IKATP) and reducing inward rectifier potassium currents. In isolated hearts of three different mammalian species, intracoronary chloroquine perfusion reduced fibrillatory frequency (atrial or ventricular), and effectively terminated the arrhythmia with resumption of sinus rhythm. In patch-clamp experiments chloroquine blocked IK1, IKACh, and IKATP. Comparative molecular modeling and ligand docking of chloroquine in the intracellular domains of Kir2.1, Kir3.1, and Kir6.2 suggested that chloroquine blocks or reduces potassium flow by interacting with negatively charged amino acids facing the ion permeation vestibule of the channel in question. These results open a novel path toward discovering antiarrhythmic pharmacophores that target specific residues of the cytoplasmic domain of inward rectifier potassium channels.—Noujaim, S. F., Stuckey, J. A., Ponce-Balbuena, D., Ferrer-Villada, T., López-Izquierdo, A., Pandit, S., Calvo, C. J., Grzeda, K. R., Berenfeld, O., Sánchez Chapula, J. A., Jalife, J. Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets. PMID:20585026

Seasonal acclimatization of the cardiac potassium currents (IK1 and IKr) in an arctic marine teleost, the navaga cod (Eleginus navaga).

PubMed

Abramochkin, Denis V; Vornanen, Matti

2015-12-01

Several freshwater fishes of north-temperate latitudes exhibit marked seasonal changes in cardiac action potential (AP) waveform as an outcome of temperature-dependent changes in the density of delayed rectifiers (IKr, IKs) and inward rectifier (IK1) potassium currents. Thus far, ionic mechanisms of cardiac excitability in arctic marine fishes have not been examined. To this end we examined ventricular AP and the role of two major potassium currents (IK1, IKr) in repolarization of cardiac AP in winter-acclimatized (WA, caught in March) and summer-acclimatized (SA, caught in September) navaga cod (Eleginus navaga) of the White Sea. The duration of ventricular AP of WA navaga at 3 °C (APD50 = 659.5 ± 32.8 ms) was similar to the AP duration of SA navaga at 12 °C (APD50 = 543.9 ± 14.6 ms) (p > 0.05) indicating complete thermal compensation of AP duration. This acclimation effect was associated with strong up-regulation of the cardiac potassium currents in winter. Densities of ventricular IK1 (at -120 mV) and IKr (at +50 mV) of the WA navaga at 3 °C were 2.9 times and 2.8 times, respectively, higher than those of the SA navaga at 12 °C, thus indicating marked thermal overcompensation. Qualitatively similar results were obtained from atrial myocytes. Seasonal changes in IK1 and IKr are more than sufficient to explain the complete thermal compensation of ventricular AP duration. The excellent acclimation capacity of cardiac excitability of the navaga cod is probably needed to maintain high cardiac performance at subzero temperatures in winter and to increase thermal resilience of cardiac function under seasonally variable arctic temperature conditions.

Molecular mechanism underlying β1 regulation in voltage- and calcium-activated potassium (BK) channels

PubMed Central

Castillo, Karen; Contreras, Gustavo F.; Pupo, Amaury; Torres, Yolima P.; Neely, Alan; González, Carlos; Latorre, Ramon

2015-01-01

Being activated by depolarizing voltages and increases in cytoplasmic Ca2+, voltage- and calcium-activated potassium (BK) channels and their modulatory β-subunits are able to dampen or stop excitatory stimuli in a wide range of cellular types, including both neuronal and nonneuronal tissues. Minimal alterations in BK channel function may contribute to the pathophysiology of several diseases, including hypertension, asthma, cancer, epilepsy, and diabetes. Several gating processes, allosterically coupled to each other, control BK channel activity and are potential targets for regulation by auxiliary β-subunits that are expressed together with the α (BK)-subunit in almost every tissue type where they are found. By measuring gating currents in BK channels coexpressed with chimeras between β1 and β3 or β2 auxiliary subunits, we were able to identify that the cytoplasmic regions of β1 are responsible for the modulation of the voltage sensors. In addition, we narrowed down the structural determinants to the N terminus of β1, which contains two lysine residues (i.e., K3 and K4), which upon substitution virtually abolished the effects of β1 on charge movement. The mechanism by which K3 and K4 stabilize the voltage sensor is not electrostatic but specific, and the α (BK)-residues involved remain to be identified. This is the first report, to our knowledge, where the regulatory effects of the β1-subunit have been clearly assigned to a particular segment, with two pivotal amino acids being responsible for this modulation. PMID:25825713

Patiromer: A Review in Hyperkalaemia.

PubMed

Kim, E S; Deeks, Emma D

2016-08-01

Patiromer (Veltassa(™)) for oral suspension is a sodium-free potassium binder that is approved in the USA for the treatment of hyperkalaemia. In clinical trials, patiromer significantly reduced serum potassium levels from baseline to week 4 in patients with chronic kidney disease (CKD) and mild to severe hyperkalaemia (OPAL-HK), or CKD, mild to moderate hyperkalaemia and type 2 diabetes mellitus (AMETHYST-DN), who were receiving renin-angiotensin-aldosterone system inhibitors (RAASis; drugs that inhibit the renal excretion of potassium). Among patients in OPAL-HK who had moderate to severe hyperkalaemia at baseline and normokalaemia on patiromer and RAASis at week 4, continuing patiromer for a further 8 weeks maintained reductions in potassium levels more effectively than switching to placebo (i.e. withdrawing patiromer); consequently, fewer patiromer than placebo recipients experienced recurrent hyperkalaemia during this period. Furthermore, almost all patiromer (vs. less than half of placebo) recipients were still receiving RAASi therapy at the end of this trial. In AMETHYST-DN, the significant reduction from baseline in serum potassium levels seen at week 4 was sustained for up to 52 weeks. Patiromer was generally well tolerated in these trials, with no treatment-related serious adverse events or deaths. Commonly occurring treatment-related adverse events include mild to moderate constipation and hypomagnesaemia, and there is a low risk of hypokalaemia. In conclusion, oral patiromer is a useful new option for patients with hyperkalaemia.

Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in rat dorsal root ganglion neurons.

PubMed

Binzen, U; Greffrath, W; Hennessy, S; Bausen, M; Saaler-Reinhardt, S; Treede, R-D

2006-10-13

Potassium channels contribute to basic neuronal excitability and modulation. Here, we examined expression patterns of the voltage-gated potassium channel Kv1.4, the nociceptive transduction channels TRPV1 and TRPV2 as well as the putative anti-nociceptive cannabinoid receptor CB1 by immunofluorescence double-labelings in sections of rat dorsal root ganglia (DRGs). Kv1.4, TRPV1 and CB1 were each detected in about one third of neurons (35.7+/-0.5%, 29.4+/-1.1% and 36.4+/-0.5%, respectively, mean diameter 19.1+/-0.3 microm). TRPV2 was present in 4.4+/-0.4% of all neurons that were significantly larger in diameter (27.4+/-0.7 microm; P < 0.001). Antibody double-labeling revealed that the majority of Kv1.4-positive neurons co-expressed TRPV1 (73.9+/-1.5%) whereas none expressed TRPV2. The largest overlap was found with CB1 (93.1+/-0.1%). CB1 expression resembled that seen for Kv1.4 since the majority of neurons expressing CB1-protein also expressed TRPV1 (69.4+/-6.5%) but not TRPV2 (0.6+/-0.3%). When CB1-mRNA was detected using in situ hybridizations an additional subset of larger neurons was labeled including 82.4+/-17.7% of the TRPV2 expressing neurons. However, co-localization of Kv1.4 with CB1-mRNA (92%, mean diameter: 18.5 microm) was essentially the same as with CB1-protein. The almost complete overlap of CB1 and Kv1.4 in nociceptive DRG neurons suggests a functional synergistic action between Kv1.4 and CB1. The potassium channel may have two important roles in nociception. As the molecular basis of A-type current it could be involved in the control of repetitive discharges at peripheral terminals and as a downstream signal transduction site of CB1 in the control of presynaptic transmitter release at central terminals.

Potassium Homeostasis in Health and Disease: A Scientific Workshop Cosponsored by the National Kidney Foundation and the American Society of Hypertension.

PubMed

Kovesdy, Csaba P; Appel, Lawrence J; Grams, Morgan E; Gutekunst, Lisa; McCullough, Peter A; Palmer, Biff F; Pitt, Bertram; Sica, Dominic A; Townsend, Raymond R

2017-12-01

While much emphasis, and some controversy, centers on recommendations for sodium intake, there has been considerably less interest in recommendations for dietary potassium intake, in both the general population and patients with medical conditions, particularly acute and chronic kidney disease. Physiology literature and cohort studies have noted that the relative balance in sodium and potassium intakes is an important determinant of many of the sodium-related outcomes. A noteworthy characteristic of potassium in clinical medicine is the extreme concern shared by many practitioners when confronted by a patient with hyperkalemia. Fear of this often asymptomatic finding limits enthusiasm for recommending potassium intake and often limits the use of renin-angiotensin-aldosterone system blockers in patients with heart failure and chronic kidney diseases. New agents for managing hyperkalemia may alter the long-term management of heart failure and the hypertension, proteinuria, and further function loss in chronic kidney diseases. In this jointly sponsored effort between the American Society of Hypertension and the National Kidney Foundation, 3 panels of researchers and practitioners from various disciplines discussed and summarized current understanding of the role of potassium in health and disease, focusing on cardiovascular, nutritional, and kidney considerations associated with both hypo- and hyperkalemia. Copyright © 2017 Published jointly in American Journal of Kidney Diseases and the Journal of the American society of Hypertension by Elsevier Inc, on behalf of the National Kidney Foundation and the American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

The mammalian spot test and its use for the testing of potential carcinogenicity of welding fume particles and hexavalent chromium.

PubMed

Knudsen, I

1980-07-01

Welding fume particles, potassium chromate and cyclophosphamide are tested in the mammalian spot test. Female mice C57BL/6J/BOM9 weeks old have been mated to T-stock male mice and treated with welding fume particles 100 mg/kg, potassium chromate 20 or 10 mg/kg, or cyclophosphamide 10 or 2.5 mg/kg intraperitoneally at day 8, 9 and 10 of pregnancy. The fur of the offspring was checked week 2 through week 5 after birth for coloured spots. The characterisation of the different types of spots are discussed. Welding fume particles 100 mg/kg and potassium chromate 10 mg/kg induce approximately to the same extent as cyclophosphamde 2.5 mg/kg, grayish or brownish spots in tvo screening test for mutagenic and carcinogenic potential of chemicals. The positive results for potassium chromate and cyclophosphamide are in agreement with previous in vitro experiments and confirm the sensitivity of the test. The effect of welding fume particles in this in vivo system suggests a potential risk for humans directly exposed to welding fumes.

Effect of Bromide-Hypochlorite Bactericides on Microorganisms1

PubMed Central

Shere, Lewis; Kelley, Maurice J.; Richardson, J. Harold

1962-01-01

A new principle in compounding stable, granular bactericidal products led to unique combinations of a water-soluble inorganic bromide salt with a hypochlorite-type disinfectant of either inorganic or organic type. Microbiological results are shown for an inorganic bactericide composed of chlorinated trisodium phosphate containing 3.1% “available chlorine” and 2% potassium bromide, and for an organic bactericide formulated from sodium dichloroisocyanurate so as to contain 13.4% “available chlorine” and 8% potassium bromide. Comparison of these products with their nonbromide counterparts are reported for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Streptococcus lactis, Aerobacter aerogenes, and Proteus vulgaris. Test methods employed were the Chambers test, the A.O.A.C. Germicidal and Detergent Sanitizer-Official test, and the Available Chlorine Germicidal Equivalent Concentration test. The minimal killing concentrations for the bromide-hypochlorite bactericides against this variety of organisms were reduced by a factor 2 to 24 times those required for similar hypochlorite-type disinfectants not containing the bromide. PMID:13977149

Improving a Complement-fixation Test for Equine Herpesvirus Type-1 by Pretreating Sera with Potassium Periodate to Reduce Non-specific Hemolysis

PubMed Central

BANNAI, Hiroshi; NEMOTO, Manabu; TSUJIMURA, Koji; YAMANAKA, Takashi; KONDO, Takashi; MATSUMURA, Tomio

2013-01-01

Non-specific hemolysis has often been observed during complement-fixation (CF) tests for equine herpesvirus type-1 (EHV-1), even when the sera have virus-specific CF antibodies. This phenomenon has also been reported in CF tests for various infectious diseases of swine. We found that the sera from 22 of 85 field horses (25.9%) showed non-specific hemolysis during conventional CF testing for EHV-1. Because pretreatment of swine sera with potassium periodate (KIO4) improves the CF test for swine influenza, we applied this method to horse sera. As we expected, horse sera treated with KIO4 did not show non-specific hemolysis in the EHV-1 CF test, and precise determination of titers was achieved. PMID:24834005

The gating cycle of a K+ channel at atomic resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuello, Luis G.; Cortes, D. Marien; Perozo, Eduardo

C-type inactivation in potassium channels helps fine-tune long-term channel activity through conformational changes at the selectivity filter. Here, through the use of cross-linked constitutively open constructs, we determined the structures of KcsA’s mutants that stabilize the selectivity filter in its conductive (E71A, at 2.25 Å) and deep C-type inactivated (Y82A at 2.4 Å) conformations. These structural snapshots represent KcsA’s transient open-conductive (O/O) and the stable open deep C-type inactivated states (O/I), respectively. The present structures provide an unprecedented view of the selectivity filter backbone in its collapsed deep C-type inactivated conformation, highlighting the close interactions with structural waters and themore » local allosteric interactions that couple activation and inactivation gating. Together with the structures associated with the closed-inactivated state (C/I) and in the well-known closed conductive state (C/O), this work recapitulates, at atomic resolution, the key conformational changes of a potassium channel pore domain as it progresses along its gating cycle.« less

Fibrous Carbon-Metallic Materials and a Method of Manufacturing Carbon-Metallic Fibrous Materials,

DTIC Science & Technology

1983-05-12

for obtaining solid compositions. Example 1. A carbon unwoven fabric obtained through carbonization of polyacrylic fabric is polarized anodically in...a l.5n solution of potassium carbonate, using a current load of l5mA/cm2 for 30 seconds, and then is cathodically polarized in the same solution using...bathcontaining 30g/l Of CuCO3’Cu(OH)2, 100g/1 of potassium -sodium tartrate,50g/l of KOH and 25g/l of 40% formalin. • i The length of time in the

Signaling of pigment-dispersing factor (PDF) in the Madeira cockroach Rhyparobia maderae.

PubMed

Wei, Hongying; Yasar, Hanzey; Funk, Nico W; Giese, Maria; Baz, El-Sayed; Stengl, Monika

2014-01-01

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca²⁺ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca²⁺ baseline concentration and frequency of oscillating Ca²⁺ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca²⁺ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1-4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca²⁺ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K⁺ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K⁺ and Na⁺ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance.

M-type K+ currents in rat cultured thoracolumbar sympathetic neurones and their role in uracil nucleotide-evoked noradrenaline release

PubMed Central

Nörenberg, W; von Kügelgen, I; Meyer, A; Illes, P; Starke, K

2000-01-01

Cultured sympathetic neurones are depolarized and release noradrenaline in response to extracellular ATP, UDP and UTP. We examined the possibility that, in neurones cultured from rat thoracolumbar sympathetic ganglia, inhibition of the M-type potassium current might underlie the effects of UDP and UTP. Reverse transcriptase-polymerase chain reaction indicated that the cultured cells contained mRNA for P2Y2-, P2Y4- and P2Y6-receptors as well as for the KCNQ2- and KCNQ3-subunits which have been suggested to assemble into M-channels. In cultures of neurones taken from newborn as well as from 10 day-old rats, oxotremorine, the M-channel blocker Ba2+ and UDP all released previously stored [3H]-noradrenaline. The neurones possessed M-currents, the kinetic properties of which were similar in neurones from newborn and 9–12 day-old rats. UDP, UTP and ATP had no effect on M-currents in neurones prepared from newborn rats. Oxotremorine and Ba2+ substantially inhibited the current. ATP also had no effect on the M-current in neurones prepared from 9–12 day-old rats. Oxotremorine and Ba2+ again caused marked inhibition. In contrast to cultures from newborn animals, UDP and UTP attenuated the M-current in neurones from 9–12 day-old rats; however, the maximal inhibition was less than 30%. The results indicate that inhibition of the M-current is not involved in uracil nucleotide-induced transmitter release from rat cultured sympathetic neurones during early development. M-current inhibition may contribute to release at later stages, but only to a minor extent. The mechanism leading to noradrenaline release by UDP and UTP remains unknown. PMID:10683196

Physiological roles of Kv2 channels in entorhinal cortex layer II stellate cells revealed by Guangxitoxin‐1E

PubMed Central

Hönigsperger, Christoph; Nigro, Maximiliano J.

2016-01-01

Key points Kv2 channels underlie delayed‐rectifier potassium currents in various neurons, although their physiological roles often remain elusive. Almost nothing is known about Kv2 channel functions in medial entorhinal cortex (mEC) neurons, which are involved in representing space, memory formation, epilepsy and dementia.Stellate cells in layer II of the mEC project to the hippocampus and are considered to be space‐representing grid cells. We used the new Kv2 blocker Guangxitoxin‐1E (GTx) to study Kv2 functions in these neurons.Voltage clamp recordings from mEC stellate cells in rat brain slices showed that GTx inhibited delayed‐rectifier K+ current but not transient A‐type current.In current clamp, GTx had multiple effects: (i) increasing excitability and bursting at moderate spike rates but reducing firing at high rates; (ii) enhancing after‐depolarizations; (iii) reducing the fast and medium after‐hyperpolarizations; (iv) broadening action potentials; and (v) reducing spike clustering.GTx is a useful tool for studying Kv2 channels and their functions in neurons. Abstract The medial entorhinal cortex (mEC) is strongly involved in spatial navigation, memory, dementia and epilepsy. Although potassium channels shape neuronal activity, their roles in mEC are largely unknown. We used the new Kv2 blocker Guangxitoxin‐1E (GTx; 10–100 nm) in rat brain slices to investigate Kv2 channel functions in mEC layer II stellate cells (SCs). These neurons project to the hippocampus and are considered to be grid cells representing space. Voltage clamp recordings from SCs nucleated patches showed that GTx inhibited a delayed rectifier K+ current activating beyond –30 mV but not transient A‐type current. In current clamp, GTx (i) had almost no effect on the first action potential but markedly slowed repolarization of late spikes during repetitive firing; (ii) enhanced the after‐depolarization (ADP); (iii) reduced fast and medium after‐hyperpolarizations (AHPs); (iv) strongly enhanced burst firing and increased excitability at moderate spike rates but reduced spiking at high rates; and (v) reduced spike clustering and rebound potentials. The changes in bursting and excitability were related to the altered ADPs and AHPs. Kv2 channels strongly shape the activity of mEC SCs by affecting spike repolarization, after‐potentials, excitability and spike patterns. GTx is a useful tool and may serve to further clarify Kv2 channel functions in neurons. We conclude that Kv2 channels in mEC SCs are important determinants of intrinsic properties that allow these neurons to produce spatial representation. The results of the present study may also be important for the accurate modelling of grid cells. PMID:27562026

The selective A-type K+ current blocker Tx3-1 isolated from the Phoneutria nigriventer venom enhances memory of naïve and Aβ(25-35)-treated mice.

PubMed

Gomes, Guilherme M; Dalmolin, Gerusa D; Cordeiro, Marta do Nascimento; Gomez, Marcus V; Ferreira, Juliano; Rubin, Maribel A

2013-12-15

Potassium channels regulate many neuronal functions, including neuronal excitability and synaptic plasticity, contributing, by these means, to mnemonic processes. In particular, A-type K(+) currents (IA) play a key role in hippocampal synaptic plasticity. Therefore, we evaluated the effect of the peptidic toxin Tx3-1, a selective blocker of IA currents, extracted from the venom of the spider Phoneutria nigriventer, on memory of mice. Administration of Tx3-1 (i.c.v., 300 pmol/site) enhanced both short- and long-term memory consolidation of mice tested in the novel object recognition task. In comparison, 4-aminopyridine (4-AP; i.c.v., 30-300 pmol/site), a non-selective K(+) channel blocker did not alter long-term memory and caused toxic side effects such as circling, freezing and tonic-clonic seizures. Moreover, Tx3-1 (i.c.v., 10-100 pmol/site) restored memory of Aβ25-35-injected mice, and exhibited a higher potency to improve memory of Aβ25-35-injected mice when compared to control group. These results show the effect of the selective blocker of IA currents Tx3-1 in both short- and long-term memory retention and in memory impairment caused by Aβ25-35, reinforcing the role of IA in physiological and pathological memory processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Potassium Channels in Epilepsy

PubMed Central

Köhling, Rüdiger; Wolfart, Jakob

2016-01-01

This review attempts to give a concise and up-to-date overview on the role of potassium channels in epilepsies. Their role can be defined from a genetic perspective, focusing on variants and de novo mutations identified in genetic studies or animal models with targeted, specific mutations in genes coding for a member of the large potassium channel family. In these genetic studies, a demonstrated functional link to hyperexcitability often remains elusive. However, their role can also be defined from a functional perspective, based on dynamic, aggravating, or adaptive transcriptional and posttranslational alterations. In these cases, it often remains elusive whether the alteration is causal or merely incidental. With ∼80 potassium channel types, of which ∼10% are known to be associated with epilepsies (in humans) or a seizure phenotype (in animals), if genetically mutated, a comprehensive review is a challenging endeavor. This goal may seem all the more ambitious once the data on posttranslational alterations, found both in human tissue from epilepsy patients and in chronic or acute animal models, are included. We therefore summarize the literature, and expand only on key findings, particularly regarding functional alterations found in patient brain tissue and chronic animal models. PMID:27141079

Sodium and potassium in the lunar atmosphere

NASA Technical Reports Server (NTRS)

Potter, A. E.; Morgan, T. H.

1991-01-01

The discovery that sodium and potassium vapor can be observed in the lunar atmosphere using ground-based telescopes has opened up a field of investigation that was closed after the last Apollo mission to the Moon. Sodium has been detected at altitudes up to 1500 km above the surface. This implies a high effective temperature for sodium, of the order of 1000 K. However, there is some evidence for two populations of sodium and potassium, one at temperatures corresponding to the surface, and another corresponding to high temperatures. The sources for the lunar atmosphere are not understood. Meteoric bombardment of the surface, solar wind sputtering of the surface, and photo-sputtering of the surface have all been suggested as possible sources for the lunar atmosphere. One of the objectives of the current research is to test different hypotheses by measurements of the atmosphere under different conditions of solar illumination and shielding from the solar wind by the Earth.

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

PubMed Central

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

Preliminary assessment of a potassium-steam-gas vapor cycle for better fuel economy and reduced thermal pollution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraas, A.P.

1971-08-01

The facts of fuel supply limitations, environmental quality demands, and spiraling electric generating costs strongly favor development of electric power plants that simultaneously run at higher efficiency, i.e., higher temperature, use to advantage clean fuels, and have as low a capital cost as possible. Both fuel supply and thermal pollution considerations that are becoming progressively more important strongly favor the development of a higher temperature, and more efficient, thermodynamic cycle for electric power plants. About 200,000 hr of operation of boiling potassium systems, including over 15,000 hr of potassium vapor turbine operation under the space power plant program, suggest thatmore » a potassium vapor topping cycle with a turbine inlet temperature of approximately 1500/sup 0/F merits consideration. A design study has been carried out to indicate the size, cost, and development problems of the new types of equipment required. The results indicate that a potassium vapor cycle superimposed on a conventional 1050/sup 0/F steam cycle would give an overall thermal efficiency of about 54% as compared to only 40% from a conventional steam cycle. Thus the proposed system would have a fuel consumption only 75% and a heat rejection rate only 50% that of a conventional plant. The system requires clean fuel, and takes advantage of the present trend toward eliminating SO/sub 2/, NO/sub x/ and ash emissions. Surprisingly, at first sight, the assessment at this stage shows that the capital cost may be less than that of a conventional plant. The main reason for this is use of pressurized combustion, which leads to a much smaller combustor, and thin tube walls to contain potassium at about the same pressure.« less

[Evaluation of soil quality under different land use types in Naban River watershed, Yunnan Province of Southwest China].

PubMed

Xie, Jin; Li, Zhao-Li; Li, Yong-Mei; Guo, Fang-Fang

2011-12-01

Eighty-six topsoil (0-20 cm) samples were collected from 8 land use types (natural forest land, maize field, tea garden, paddy field, rubber plantation, flax field, banana plantation, and sugarcane field) in the Naban River Watershed National Nature Reserve and its surrounding areas, and the soil physical and chemical properties were analyzed, aimed to study the effects of land use type on the soil quality by the method of soil quality index (SQI). Comparing with natural forest land, all the cultivated lands had somewhat decreased soil organic matter content and higher soil bulk density, and the soil bulk density was significantly higher in tea garden, paddy field, rubber plantation, and banana plantation. In cultivated lands, fertilization and reclamation made the soil available potassium and phosphorus contents maintained at a higher level, probably due to the input of mineral potassium and phosphorus and the decomposition of soil organic matter. The SQI of the 8 land use types was in the order of flax field (0.595) > natural forest land (0.532) > maize field (0.516) > banana plantation (0.485) tea garden (0.480) sugarcane field (0.463) > paddy field (0.416) > rubber plantation (0.362). The soils in higher altitude production demonstration areas (1614 +/-115 m) had significant higher SQI, compared to the soils in lower altitude buffer areas (908 +/- 98 m) and junction areas (926 +/- 131 m). Among the 8 land use types, the rubber plantation in lower altitude areas had the lowest SQI, due to the lower soil organic matter and available potassium and phosphorus contents and the highest soil bulk density. Application of organic manure or intercropping with leguminous plants could be an available practice to improve the soil quality of the rubber plantation.

Activity-Dependent Gating of Calcium Spikes by A-type K+ Channels Controls Climbing Fiber Signaling in Purkinje Cell Dendrites

PubMed Central

Otsu, Yo; Marcaggi, Païkan; Feltz, Anne; Isope, Philippe; Kollo, Mihaly; Nusser, Zoltan; Mathieu, Benjamin; Kano, Masanobu; Tsujita, Mika; Sakimura, Kenji; Dieudonné, Stéphane

2014-01-01

Summary In cerebellar Purkinje cell dendrites, heterosynaptic calcium signaling induced by the proximal climbing fiber (CF) input controls plasticity at distal parallel fiber (PF) synapses. The substrate and regulation of this long-range dendritic calcium signaling are poorly understood. Using high-speed calcium imaging, we examine the role of active dendritic conductances. Under basal conditions, CF stimulation evokes T-type calcium signaling displaying sharp proximodistal decrement. Combined mGluR1 receptor activation and depolarization, two activity-dependent signals, unlock P/Q calcium spikes initiation and propagation, mediating efficient CF signaling at distal sites. These spikes are initiated in proximal smooth dendrites, independently from somatic sodium action potentials, and evoke high-frequency bursts of all-or-none fast-rising calcium transients in PF spines. Gradual calcium spike burst unlocking arises from increasing inactivation of mGluR1-modulated low-threshold A-type potassium channels located in distal dendrites. Evidence for graded activity-dependent CF calcium signaling at PF synapses refines current views on cerebellar supervised learning rules. PMID:25220810

Activity-dependent gating of calcium spikes by A-type K+ channels controls climbing fiber signaling in Purkinje cell dendrites.

PubMed

Otsu, Yo; Marcaggi, Païkan; Feltz, Anne; Isope, Philippe; Kollo, Mihaly; Nusser, Zoltan; Mathieu, Benjamin; Kano, Masanobu; Tsujita, Mika; Sakimura, Kenji; Dieudonné, Stéphane

2014-10-01

In cerebellar Purkinje cell dendrites, heterosynaptic calcium signaling induced by the proximal climbing fiber (CF) input controls plasticity at distal parallel fiber (PF) synapses. The substrate and regulation of this long-range dendritic calcium signaling are poorly understood. Using high-speed calcium imaging, we examine the role of active dendritic conductances. Under basal conditions, CF stimulation evokes T-type calcium signaling displaying sharp proximodistal decrement. Combined mGluR1 receptor activation and depolarization, two activity-dependent signals, unlock P/Q calcium spikes initiation and propagation, mediating efficient CF signaling at distal sites. These spikes are initiated in proximal smooth dendrites, independently from somatic sodium action potentials, and evoke high-frequency bursts of all-or-none fast-rising calcium transients in PF spines. Gradual calcium spike burst unlocking arises from increasing inactivation of mGluR1-modulated low-threshold A-type potassium channels located in distal dendrites. Evidence for graded activity-dependent CF calcium signaling at PF synapses refines current views on cerebellar supervised learning rules. Copyright © 2014 Elsevier Inc. All rights reserved.

Extraordinary Off-Stoichiometric Bismuth Telluride for Enhanced n-Type Thermoelectric Power Factor.

PubMed

Park, Kunsu; Ahn, Kyunghan; Cha, Joonil; Lee, Sanghwa; Chae, Sue In; Cho, Sung-Pyo; Ryee, Siheon; Im, Jino; Lee, Jaeki; Park, Su-Dong; Han, Myung Joon; Chung, In; Hyeon, Taeghwan

2016-11-02

Thermoelectrics directly converts waste heat into electricity and is considered a promising means of sustainable energy generation. While most of the recent advances in the enhancement of the thermoelectric figure of merit (ZT) resulted from a decrease in lattice thermal conductivity by nanostructuring, there have been very few attempts to enhance electrical transport properties, i.e., the power factor. Here we use nanochemistry to stabilize bulk bismuth telluride (Bi 2 Te 3 ) that violates phase equilibrium, namely, phase-pure n-type K 0.06 Bi 2 Te 3.18 . Incorporated potassium and tellurium in Bi 2 Te 3 far exceed their solubility limit, inducing simultaneous increase in the electrical conductivity and the Seebeck coefficient along with decrease in the thermal conductivity. Consequently, a high power factor of ∼43 μW cm -1 K -2 and a high ZT > 1.1 at 323 K are achieved. Our current synthetic method can be used to produce a new family of materials with novel physical and chemical characteristics for various applications.

Voltage-gated currents in identified rat olfactory receptor neurons.

PubMed

Trombley, P Q; Westbrook, G L

1991-02-01

Whole-cell recording techniques were used to characterize voltage-gated membrane currents in neonatal rat olfactory receptor neurons (ORNs) in cell culture. Mature ORNs were identified in culture by their characteristic bipolar morphology, by retrograde labeling techniques, and by olfactory marker protein (OMP) immunoreactivity. ORNs did not have spontaneous activity, but fired action potentials to depolarizing current pulses. Action potentials were blocked by tetrodotoxin (TTX), which contrasts with the TTX-resistant action potentials in salamander olfactory receptor cells (e.g., Firestein and Werblin, 1987). Prolonged, suprathreshold current pulses evoked only a single action potential; however, repetitive firing up to 35 Hz could be elicited by a series of brief depolarizing pulses. Under voltage clamp, the TTX-sensitive sodium current had activation and inactivation properties similar to other excitable cells. In TTX and 20 mM barium, sustained inward current were evoked by voltage steps positive to -30 mV. This current was blocked by Cd (100 microM) and by nifedipine (IC50 = 368 nM) consistent with L-type calcium channels in other neurons. No T-type calcium current was observed. Voltage steps positive to -20 mV also evoked an outward current that did not inactivate during 100-msec depolarizations. Tail current analysis of this current was consistent with a selective potassium conductance. The outward current was blocked by external tetraethylammonium but was unaffected by Cd or 4-aminopyridine (4-AP) or by removal of external calcium. A transient outward current was not observed. The 3 voltage-dependent conductances in cultured rat ORNs appear to be sufficient for 2 essential functions: action potential generation and transmitter release. As a single odorant-activated channel can trigger an action potential (e.g., Lynch and Barry, 1989), the repetitive firing seen with brief depolarizing pulses suggests that ORNs do not integrate sensory input, but rather act as high-fidelity relays such that each opening of an odorant-activated channel reaches the olfactory bulb glomeruli as an action potential.

[Hyperkalemia - current therapuetic strategies].

PubMed

Głogowski, Tomasz; Wojtaszek, Ewa

Hyperkalemia is a medical emergency that requires immediate therapy, followed by interventions aimed at preventing its recurrence. Hyperkalemia occurs especially frequently in patients with chronic kidney disease (CKD), in part because of impaired kidney function and in part due to coexisting comorbidities such as diabetes or heart failure and the medications used to treat them, first of all the inhibitors of renin-angiotensin-aldosterone system (RAASi). Both acute and chronic management of hyperkalemia are equally important, though, with currently available therapeutic possibilities, the effective restoration of potassium homeostasis are in fact limited to the correction of its triggers. The emergence of new medications (patiromer and ZS-9) could lead to a therapeutic paradigm shift from intermittent treatment of incidentally discovered hyperkalemia toward preventive measures preventing fluctuations in serum potassium levels and enabling the continuation of beneficial, but hyperkalemia inducing agents.

A novel muscarinic receptor-independent mechanism of KCNQ2/3 potassium channel blockade by Oxotremorine-M.

PubMed

Zwart, Ruud; Reed, Hannah; Clarke, Sophie; Sher, Emanuele

2016-11-15

Inhibition of KCNQ (Kv7) potassium channels by activation of muscarinic acetylcholine receptors has been well established, and the ion currents through these channels have been long known as M-currents. We found that this cross-talk can be reconstituted in Xenopus oocytes by co-transfection of human recombinant muscarinic M1 receptors and KCNQ2/3 potassium channels. Application of the muscarinic acetylcholine receptor agonist Oxotremorine-methiodide (Oxo-M) between voltage pulses to activate KCNQ2/3 channels caused inhibition of the subsequent KCNQ2/3 responses. This effect of Oxo-M was blocked by the muscarinic acetylcholine receptor antagonist atropine. We also found that KCNQ2/3 currents were inhibited when Oxo-M was applied during an ongoing KCNQ2/3 response, an effect that was not blocked by atropine, suggesting that Oxo-M inhibits KCNQ2/3 channels directly. Indeed, also in oocytes that were transfected with only KCNQ2/3 channels, but not with muscarinic M1 receptors, Oxo-M inhibited the KCNQ2/3 response. These results show that besides the usual muscarinic acetylcholine receptor-mediated inhibition, Oxo-M also inhibits KCNQ2/3 channels by a direct mechanism. We subsequently tested xanomeline, which is a chemically distinct muscarinic acetylcholine receptor agonist, and oxotremorine, which is a close analogue of Oxo-M. Both compounds inhibited KCNQ2/3 currents via activation of M1 muscarinic acetylcholine receptors but, in contrast to Oxo-M, they did not directly inhibit KCNQ2/3 channels. Xanomeline and oxotremorine do not contain a positively charged trimethylammonium moiety that is present in Oxo-M, suggesting that such a charged moiety could be a crucial component mediating this newly described direct inhibition of KCNQ2/3 channels. Copyright © 2016 Elsevier B.V. All rights reserved.

Potassium vapor assisted preparation of highly graphitized hierarchical porous carbon for high rate performance supercapacitors

NASA Astrophysics Data System (ADS)

Liu, Zheng; Zeng, Ying; Tang, Qunli; Hu, Aiping; Xiao, Kuikui; Zhang, Shiying; Deng, Weina; Fan, Binbin; Zhu, Yanfei; Chen, Xiaohua

2017-09-01

Ultrahigh graphitized carbon microspheres with rich hierarchical pores (AGHPCM-1) have been successfully synthesized through the one-step activation-carbonization strategy (OACS) with porous sulfonated poly-divinylbenzene as the carbon precursor, iron as the hard template and catalyst, and potassium hydroxide (KOH) as activation agent. Through the XRD, TEM, Raman and BET analysis, AGHPCM-1 shows very high graphitization degree and rich micro-, meso- and macro-pores. More importantly, the mechanism for KOH to improve the graphitization degree of carbon materials in OACS has been illustrated by the thermodynamical theory. The tremendous heat releasing from the reaction between the catalyst precursor of Fe2O3 and potassium vapor plays a key role in the formation of graphitized carbon. It may provide a general direction to prepare highly graphitized porous carbon at a moderate temperature. Integrating the advantages of high graphitization degree and rich hierarchical porous structure, the AGHPCM-1 exhibits an excellent rate performance with a response to up to the high current density of 150 A g-1 and high scan rate of 2000 mV s-1. No obvious capacitance decay can be observed after 10000 charge/discharge cycles even at the high current density of 20 A g-1.

Availability of two self-administered diet history questionnaires for pregnant Japanese women: A validation study using 24-hour urinary markers.

PubMed

Shiraishi, Mie; Haruna, Megumi; Matsuzaki, Masayo; Murayama, Ryoko; Sasaki, Satoshi

2017-04-01

Accurate and easy dietary assessment methods that can be used during pregnancy are required in both epidemiological studies and clinical settings. To verify the utility of dietary assessment questionnaires in pregnancy, we examined the validity and reliability of a self-administered diet history questionnaire (DHQ) and a brief-type self-administered diet history questionnaire (BDHQ) to measure energy, protein, sodium, and potassium intake among pregnant Japanese women. The research was conducted at a university hospital in Tokyo, Japan, between 2010 and 2011. The urinary urea nitrogen, sodium, and potassium levels were used as reference values in the validation study. For the reliability assessment, participants completed the questionnaires twice within a 4-week interval. For the DHQ (n = 115), the correlation coefficients between survey-assessed energy-adjusted intake and urinary protein, sodium, and potassium levels were 0.359, 0.341, and 0.368, respectively; for the BDHQ (n = 112), corresponding values were 0.302, 0.314, and 0.401, respectively. The DHQ-measured unadjusted protein and potassium intake levels were significantly correlated with the corresponding urinary levels (r s  = 0.307 and r s  = 0.342, respectively). The intra-class correlation coefficients for energy, protein, sodium, and potassium between the time 1 and time 2 DHQ (n = 58) and between the time 1 and time 2 BDHQ (n = 54) ranged from 0.505 to 0.796. Both the DHQ and the BDHQ were valid and reliable questionnaires for assessing the energy-adjusted intake of protein, sodium, and potassium during pregnancy. In addition, given the observed validity of unadjusted protein and potassium intake measures, the DHQ can be a useful tool to estimate energy intake of pregnant Japanese women. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Desensitization of chemical activation by auxiliary subunits: convergence of molecular determinants critical for augmenting KCNQ1 potassium channels.

PubMed

Gao, Zhaobing; Xiong, Qiaojie; Sun, Haiyan; Li, Min

2008-08-15

Chemical openers for KCNQ potassium channels are useful probes both for understanding channel gating and for developing therapeutics. The five KCNQ isoforms (KCNQ1 to KCNQ5, or Kv7.1 to Kv7.5) are differentially localized. Therefore, the molecular specificity of chemical openers is an important subject of investigation. Native KCNQ1 normally exists in complex with auxiliary subunits known as KCNE. In cardiac myocytes, the KCNQ1-KCNE1 (IsK or minK) channel is thought to underlie the I(Ks) current, a component critical for membrane repolarization during cardiac action potential. Hence, the molecular and pharmacological differences between KCNQ1 and KCNQ1-KCNE1 channels have been important topics. Zinc pyrithione (ZnPy) is a newly identified KCNQ channel opener, which potently activates KCNQ2, KCNQ4, and KCNQ5. However, the ZnPy effects on cardiac KCNQ1 potassium channels remain largely unknown. Here we show that ZnPy effectively augments the KCNQ1 current, exhibiting an increase in current amplitude, reduction of inactivation, and slowing of both activation and deactivation. Some of these are reminiscent of effects by KCNE1. In addition, neither the heteromultimeric KCNQ1-KCNE1 channels nor native I(Ks) current displayed any sensitivity to ZnPy, indicating that the static occupancy by a KCNE subunit desensitizes the reversible effects by a chemical opener. Site-directed mutagenesis of KCNQ1 reveals that residues critical for the potentiation effects by either ZnPy or KCNE are clustered together in the S6 region overlapping with the critical gating determinants. Thus, the convergence of potentiation effects and molecular determinants critical for both an auxiliary subunit and a chemical opener argue for a mechanistic overlap in causing potentiation.

Evaluation of the Pharmacodynamic Effects of the Potassium Binder RDX7675 in Mice.

PubMed

Davidson, James P; King, Andrew J; Kumaraswamy, Padmapriya; Caldwell, Jeremy S; Korner, Paul; Blanks, Robert C; Jacobs, Jeffrey W

2018-05-01

Hyperkalemia is a common complication in patients with heart failure or chronic kidney disease, particularly those who are taking inhibitors of the renin-angiotensin-aldosterone system. RDX7675, the calcium salt of a reengineered polystyrene sulfonate-based resin, is a potassium binder that is being investigated as a novel treatment for hyperkalemia. This study evaluated the pharmacodynamic effects of RDX7675 in mice, compared to 2 current treatments, sodium polystyrene sulfonate (SPS) and patiromer. Seven groups of 8 male CD-1 mice were given either standard chow (controls) or standard chow containing 4.0% or 6.6% active moiety of RDX7675, patiromer, or SPS for 72 hours. Stool and urine were collected over the final 24 hours of treatment for ion excretion analyses. RDX7675 increased stool potassium (mean 24-hour excretion: 4.0%, 9.19 mg; 6.6%, 18.11 mg; both P < .0001) compared with controls (4.47 mg) and decreased urinary potassium (mean 24-hour excretion: 4.0%, 12.05 mg, P < .001; 6.6%, 6.68 mg, P < .0001; vs controls, 20.38 mg). The potassium-binding capacity of RDX7675 (stool potassium/gram of resin: 4.0%, 1.14 mEq/g; 6.6%, 1.32 mEq/g) was greater (all P < .0001) than for patiromer (4.0%, 0.63 mEq/g; 6.6%, 0.48 mEq/g) or SPS (4.0%, 0.73 mEq/g; 6.6% 0.55 mEq/g). RDX7675 and patiromer decreased urinary sodium (mean 24-hour excretion: 0.07-1.38 mg; all P < .001) compared to controls (5.01 mg). In contrast, SPS increased urinary sodium excretion (4.0%, 13.31 mg; 6.6%, 17.60 mg; both P < .0001) compared to controls. RDX7675 reduced intestinal potassium absorption and had a greater potassium-binding capacity than patiromer or SPS in mice. The calcium-based resins RDX7675 and patiromer reduced intestinal sodium absorption, unlike sodium-based SPS. These results support further studies in humans to confirm the potential of RDX7675 for the treatment of patients with hyperkalemia.

[Characteristics of electrophysiology and effects of ouabain on transient outward potassium current and L-type calcium current of left atrium posterior wall in rabbits].

PubMed

Wang, Teng; Huang, Cong-xin; Jiang, Hong; Tang, Qi-zhu; Yang, Bo; Li, Geng-shan

2009-12-01

To investigate the properties of electrophysiology and effects of ouabain upon transient outward potassium current (I(to)) and L-type calcium current (I(Ca-L)) of left atrium posterior wall (LAPW) and left atrium appendage tissue (LAA)in rabbit so as to provide the scientific explanations that LAPW and ouabain can enhance atrial fibrillation (AF) vulnerability through increasing electrophysiological heterogeneity and electrical remodeling of different regions of left atrium in rabbits. Atrial myocytes from LAPWs and LAAs of rabbits on an in vitro heart perfusion system were obtained by enzymatic dissociation. The whole-cell patch-clamp technique was used to assess the effects of ouabain upon I(to) and I(Ca-L). The current-voltage (I-V) curves of I(to) and I(Ca-L) in LAPW and LAA myocytes were fitted before and after ouabain administration. (1) With holding potential +50 mV and commanding potential +50 mV, the current densities of LAPW I(to) decreased slightly less than that of LAA I(to) in control groups (P > 0.05). After ouabain administration, the current densities of LAPW I(to) were significantly larger than that of LAA I(to) [(10.97 +/- 0.58) pA/pF vs (9.39 +/- 0.83) pA/pF, P < 0.05]. The I-V curve of LAPW I(to) was slightly lowered to I-V curve of LAA I(to) in control groups. But with perfusion of ouabain, the I-V curve of LAPW I(to) opposed to I-V curve of LAA I(to) significantly changed from the bottom to the top with the same upward direction. (2) With the voltage clamp protocol of I(Ca-L), the current densities of LAPW I(Ca-L) markedly decreased compared with that of LAA I(Ca-L) in control groups (P < 0.05). With the addition of ouabain, the peak of amplitude of LAPW I(Ca-L) at +20 mV obviously increased to that of LAA I(Ca-L) [(-11.13 +/- 0.99) pA/pF vs (-8.86 +/- 0.51) pA/pF, P < 0.01]. In the control groups, the I-V curve of LAPW I(Ca-L) was shifted to the bottom of all I-V curves of I(Ca-L). Through the effects of ouabain, the I-V curve of LAPW I(Ca-L) was completely upgraded to the top of other I-V curves of I(Ca-L). However, all shapes and directions of current peak of I-V curves of I(Ca-L) remained unchanged in both groups. The distribution properties of I(Ca-L) have significant difference in LAPW. Ouabain can accentuate the electrophysiological heterogeneity and electrical remodeling of I(to) and I(Ca-L) in LAPW of rabbits. It may become the triggering factor and persisting basis of AF vulnerability.

Kir 4.1 inward rectifier potassium channel is upregulated in astrocytes in a murine multiple sclerosis model.

PubMed

Mercado, Francisco; Almanza, Angélica; Rubio, Nazario; Soto, Enrique

2018-06-11

Multiple sclerosis (MS) is a high prevalence degenerative disease characterized at the cellular level by glial and neuronal cell death. The causes of cell death during the disease course are not fully understood. In this work we demonstrate that in a MS model induced by Theiler's murine encephalomyelitis virus (TMEV) infection, the inward rectifier (Kir) 4.1 potassium channel subunit is overexpressed in astrocytes. In voltage clamp experiments the inward current density from TMEV-infected astrocytes was significantly larger than in mock-infected ones. The cRNA hybridization analysis from mock- and TMEV-infected cells showed an upregulation of a potassium transport channel coding sequence. We validated this mRNA increase by RT-PCR and quantitative PCR using Kir 4.1 specific primers. Western blotting experiments confirmed the upregulation of Kir 4.1, and alignment between sequences provided the demonstration that the over-expressed gene encodes for a Kir family member. Flow cytometry showed that the Kir 4.1 protein is located mainly in the cell membrane in mock and TMEV-infected astrocytes. Our results demonstrate an increase in K + inward current in TMEV-infected glial cells, this increment may reduce the neuronal depolarization, contributing to cell resilience mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

Using Zero Balance Ultrafiltration with Dialysate as a Replacement Fluid for Hyperkalemia during Cardiopulmonary Bypass

PubMed Central

Heath, Michele; Raghunathan, Karthik; Welsby, Ian; Maxwell, Cory

2014-01-01

Abstract: Avoiding or managing hyperkalemia during cardiac surgery, especially in a patient with chronic renal insufficiency, can be challenging. Hyperkalemic cardioplegia solution is usually administered to achieve and maintain an electrical arrest of the heart. This solution eventually mixes in with the systemic circulation, contributing to elevated systemic potassium levels. Administration of packed red blood cells, hemolysis, tissue damage, and acidosis are also common causes of hyperkalemia. Current strategies to avoid or manage hyperkalemia include minimizing the volume of cardioplegia administered, shifting potassium from the extracellular into the intracellular space (by the administration of sodium bicarbonate when the pH is low and/or dextrose–insulin when effects relatively independent of serum pH are desired), using zero-balanced ultrafiltration (Z-BUF) with normal saline as the replacement fluid (to remove potassium from the body rather than simply shift the electrolyte across cellular membranes), and, occasionally, hemodialysis (1). We report the application of Z-BUF using an electrolyte-balanced, low potassium dialysate solution rather than isotonic saline to avoid a high chloride load and the potential for hyperchloremic acidosis to successfully treat hyperkalemia while on cardiopulmonary bypass. PMID:26357794

Aluminum Potassium Sulfate and Tannic Acid Injection for Hemorrhoids

PubMed Central

2012-01-01

A quick hemostatic effect, as well as sclerosing and shrinkage of hemorrhoids, can be attained when internal hemorrhoids are treated by using injection therapy with aluminum potassium sulfate and tannic acid (ALTA), the outcomes of treatment may be similar to those of a hemorrhoidectomy. However, if the type of hemorrhoid or the method of injection is not appropriate for ALTA treatment, complications peculiar to ALTA or recurrence may develop. Accordingly, sufficient understanding of the treatment mechanism of ALTA injection and repeated training for injection are required for effective use of the ALTA treatment. PMID:22606645

Endoplasmic reticulum-associated degradation of the renal potassium channel, ROMK, leads to type II Bartter syndrome.

PubMed

O'Donnell, Brighid M; Mackie, Timothy D; Subramanya, Arohan R; Brodsky, Jeffrey L

2017-08-04

Type II Bartter syndrome is caused by mutations in the renal outer medullary potassium (ROMK) channel, but the molecular mechanisms underlying this disease are poorly defined. To rapidly screen for ROMK function, we developed a yeast expression system and discovered that yeast cells lacking endogenous potassium channels could be rescued by WT ROMK but not by ROMK proteins containing any one of four Bartter mutations. We also found that the mutant proteins were significantly less stable than WT ROMK. However, their degradation was slowed in the presence of a proteasome inhibitor or when yeast cells contained mutations in the CDC48 or SSA1 gene, which is required for endoplasmic reticulum (ER)-associated degradation (ERAD). Consistent with these data, sucrose gradient centrifugation and indirect immunofluorescence microscopy indicated that most ROMK protein was ER-localized. To translate these findings to a more relevant cell type, we measured the stabilities of WT ROMK and the ROMK Bartter mutants in HEK293 cells. As in yeast, the Bartter mutant proteins were less stable than the WT protein, and their degradation was slowed in the presence of a proteasome inhibitor. Finally, we discovered that low-temperature incubation increased the steady-state levels of a Bartter mutant, suggesting that the disease-causing mutation traps the protein in a folding-deficient conformation. These findings indicate that the underlying pathology for at least a subset of patients with type II Bartter syndrome is linked to the ERAD pathway and that future therapeutic strategies should focus on correcting deficiencies in ROMK folding. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms

PubMed Central

Soto, Cristina; Canedo, Antonio

2011-01-01

Abstract Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3–4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5–2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain. PMID:21746779

Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms.

PubMed

Soto, Cristina; Canedo, Antonio

2011-09-01

Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3-4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5-2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain.

Chlorogenic acid alters the voltage-gated potassium channel currents of trigeminal ganglion neurons

PubMed Central

Zhang, Yu-Jiao; Lu, Xiao-Wen; Song, Ning; Kou, Liang; Wu, Min-Ke; Liu, Fei; Wang, Hang; Shen, Jie-Fei

2014-01-01

Chlorogenic acid (5-caffeoylquinic acid, CGA) is a phenolic compound that is found ubiquitously in plants, fruits and vegetables and is formed via the esterification of caffeic acid and quinic acid. In addition to its notable biological functions against cardiovascular diseases, type-2 diabetes and inflammatory conditions, CGA was recently hypothesized to be an alternative for the treatment of neurological diseases such as Alzheimer's disease and neuropathic pain disorders. However, its mechanism of action is unclear. Voltage-gated potassium channel (Kv) is a crucial factor in the electro-physiological processes of sensory neurons. Kv has also been identified as a potential therapeutic target for inflammation and neuropathic pain disorders. In this study, we analysed the effects of CGA on the two main subtypes of Kv in trigeminal ganglion neurons, namely, the IK,A and IK,V channels. Trigeminal ganglion (TRG) neurons were acutely disassociated from the rat TRG, and two different doses of CGA (0.2 and 1 mmol⋅L−1) were applied to the cells. Whole-cell patch-clamp recordings were performed to observe alterations in the activation and inactivation properties of the IK,A and IK,V channels. The results demonstrated that 0.2 mmol⋅L−1 CGA decreased the peak current density of IK,A. Both 0.2 mmol⋅L−1 and 1 mmol⋅L−1 CGA also caused a significant reduction in the activation and inactivation thresholds of IK,A and IK,V. CGA exhibited a strong effect on the activation and inactivation velocities of IK,A and IK,V. These findings provide novel evidence explaining the biological effects of CGA, especially regarding its neurological effects. PMID:25394592

The Combined Use of a Gas-Controlled Heat Pipe and a Copper Point to Improve the Calibration of Thermocouples up to 1100 ˚C

NASA Astrophysics Data System (ADS)

Astrua, M.; Iacomini, L.; Battuello, M.

2008-10-01

The calibration of platinum-based thermocouples from 420 °C to 1,100 ˚C is currently carried out at INRIM making use of two different apparatus: for temperatures below 930 ˚C, a potassium gas-controlled heat pipe (GCHP) is used, whereas a metal-block furnace is adopted for higher temperatures. The standard uncertainty of the reference temperature obtained in the lower temperature range is almost one order of magnitude better than in the higher temperature range. A sealed copper cell was investigated to see if it could be used to calibrate thermocouples above 930 ˚C with a lower uncertainty than our current procedures allowed. The cell was characterized with Type S and Pt/Pd thermocouples and with an HTPRT. The freezing plateaux were flat within 0.01 ˚C and lasted up to 1 h with a repeatability of 0.02 ˚C. The temperature of the cell was determined with a standard uncertainty of 0.04 ˚C. Hence, the copper cell was found to be superior to the comparator furnace for the calibration of platinum-based thermocouples because of the significant decrease in the uncertainty that it provides. An analysis was also carried out on the calibration of Pt/Pd thermocouples, and it was found that the combined use of the potassium GCHP and the Cu fixed-point cell is adequate to exploit the potential of these sensors in the range from 420 °C to 1,084 °C. A comparison with a fixed-point calibration was also made which gave rise to agreement within 0.07 ˚C between the two approaches.

Metam Sodium and Metam Potassium Fumigant Management Plan Phase 2 Templates

EPA Pesticide Factsheets

These templates provide a framework for structuring and reporting a plan for this type of pesticide product. Required data fields include application block size, buffer zone signage, soil conditions, and tarp plans.

Activation of µ-opioid receptors and block of KIR3 potassium channels and NMDA receptor conductance by l- and d-methadone in rat locus coeruleus

PubMed Central

Matsui, Aya; Williams, John T

2010-01-01

BACKGROUND AND PURPOSE Methadone activates opioid receptors to increase a potassium conductance mediated by G-protein-coupled, inwardly rectifying, potassium (KIR3) channels. Methadone also blocks KIR3 channels and N-methyl-D-aspartic acid (NMDA) receptors. However, the concentration dependence and stereospecificity of receptor activation and channel blockade by methadone on single neurons has not been characterized. EXPERIMENTAL APPROACH Intracellular and whole-cell recording were made from locus coeruleus neurons in brain slices and the activation of µ-opioid receptors and blockade of KIR3 and NMDA channels with l- and d-methadone was examined. KEY RESULTS The potency of l-methadone, measured by the amplitude of hyperpolarization was 16.5-fold higher than with d-methadone. A maximum hyperpolarization was caused by both enantiomers (∼30 mV); however, the maximum outward current measured with whole-cell voltage-clamp recording was smaller than the current induced by [Met]5enkephalin. The KIR3 conductance induced by activation of α2-adrenoceptors was decreased with high concentrations of l- and d-methadone (10–30 µM). In addition, methadone blocked the resting inward rectifying conductance (KIR). Both l- and d-methadone blocked the NMDA receptor-dependent current. The block of NMDA receptor-dependent current was voltage-dependent suggesting that methadone acted as a channel blocker. CONCLUSIONS AND IMPLICATIONS Methadone activated µ-opioid receptors at low concentrations in a stereospecific manner. KIR3 and NMDA receptor channel block was not stereospecific and required substantially higher concentrations. The separation in the concentration range suggests that the activation of µ-opioid receptors rather than the channel blocking properties mediate both the therapeutic and toxic actions of methadone. PMID:20659105

Lethal Injection for Execution: Chemical Asphyxiation?

PubMed Central

Zimmers, Teresa A; Sheldon, Jonathan; Lubarsky, David A; López-Muñoz, Francisco; Waterman, Linda; Weisman, Richard; Koniaris, Leonidas G

2007-01-01

Background Lethal injection for execution was conceived as a comparatively humane alternative to electrocution or cyanide gas. The current protocols are based on one improvised by a medical examiner and an anesthesiologist in Oklahoma and are practiced on an ad hoc basis at the discretion of prison personnel. Each drug used, the ultrashort-acting barbiturate thiopental, the neuromuscular blocker pancuronium bromide, and the electrolyte potassium chloride, was expected to be lethal alone, while the combination was intended to produce anesthesia then death due to respiratory and cardiac arrest. We sought to determine whether the current drug regimen results in death in the manner intended. Methods and Findings We analyzed data from two US states that release information on executions, North Carolina and California, as well as the published clinical, laboratory, and veterinary animal experience. Execution outcomes from North Carolina and California together with interspecies dosage scaling of thiopental effects suggest that in the current practice of lethal injection, thiopental might not be fatal and might be insufficient to induce surgical anesthesia for the duration of the execution. Furthermore, evidence from North Carolina, California, and Virginia indicates that potassium chloride in lethal injection does not reliably induce cardiac arrest. Conclusions We were able to analyze only a limited number of executions. However, our findings suggest that current lethal injection protocols may not reliably effect death through the mechanisms intended, indicating a failure of design and implementation. If thiopental and potassium chloride fail to cause anesthesia and cardiac arrest, potentially aware inmates could die through pancuronium-induced asphyxiation. Thus the conventional view of lethal injection leading to an invariably peaceful and painless death is questionable. PMID:17455994

Renal potassium physiology: integration of the renal response to dietary potassium depletion.

PubMed

Kamel, Kamel S; Schreiber, Martin; Halperin, Mitchell L

2018-01-01

We summarize the current understanding of the physiology of the renal handling of potassium (K + ), and present an integrative view of the renal response to K + depletion caused by dietary K + restriction. This renal response involves contributions from different nephron segments, and aims to diminish the rate of excretion of K + as a result of: decreasing the rate of electrogenic (and increasing the rate of electroneutral) reabsorption of sodium in the aldosterone-sensitive distal nephron (ASDN), decreasing the abundance of renal outer medullary K + channels in the luminal membrane of principal cells in the ASDN, decreasing the flow rate in the ASDN, and increasing the reabsorption of K + in the cortical and medullary collecting ducts. The implications of this physiology for the association between K + depletion and hypertension, and K + depletion and formation of calcium kidney stones are discussed. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Nonnutritive Sweeteners in Breast Milk.

PubMed

Sylvetsky, Allison C; Gardner, Alexandra L; Bauman, Viviana; Blau, Jenny E; Garraffo, H Martin; Walter, Peter J; Rother, Kristina I

2015-01-01

Nonnutritive sweeteners (NNS), including saccharin, sucralose, aspartame, and acesulfame-potassium, are commonly consumed in the general population, and all except for saccharin are considered safe for use during pregnancy and lactation. Sucralose (Splenda) currently holds the majority of the NNS market share and is often combined with acesulfame-potassium in a wide variety of foods and beverages. To date, saccharin is the only NNS reported to be found in human breast milk after maternal consumption, while there is no apparent information on the other NNS. Breast milk samples were collected from 20 lactating volunteers, irrespective of their habitual NNS intake. Saccharin, sucralose, and acesulfame-potassium were present in 65% of participants' milk samples, whereas aspartame was not detected. These data indicate that NNS are frequently ingested by nursing infants, and thus prospective clinical studies are necessary to determine whether early NNS exposure via breast milk may have clinical implications.

NONNUTRITIVE SWEETENERS IN BREAST MILK

PubMed Central

Sylvetsky, Allison C.; Gardner, Alexandra L.; Bauman, Viviana; Blau, Jenny E.; Garraffo, H. Martin; Walter, Peter J.; Rother, Kristina I.

2017-01-01

Nonnutritive sweeteners (NNS), including saccharin, sucralose, aspartame, and acesulfame-potassium, are commonly consumed in the general population, and all except for saccharin are considered safe for use during pregnancy and lactation. Sucralose (Splenda) currently holds the majority of the NNS market share and is often combined with acesulfame-potassium in a wide variety of foods and beverages. To date, saccharin is the only NNS reported to be found in human breast milk after maternal consumption, while there is no apparent information on the other NNS. Breast milk samples were collected from 20 lactating volunteers, irrespective of their habitual NNS intake. Saccharin, sucralose, and acesulfame-potassium were present in 65% of participants’ milk samples, whereas aspartame was not detected. These data indicate that NNS are frequently ingested by nursing infants, and thus prospective clinical studies are necessary to determine whether early NNS exposure via breast milk may have clinical implications. PMID:26267522

Characterization of slowly inactivating KV{alpha} current in rabbit pulmonary neuroepithelial bodies: effects of hypoxia and nicotine.

PubMed

Fu, Xiao Wen; Nurse, Colin; Cutz, Ernest

2007-10-01

Pulmonary neuroepithelial bodies (NEB) form innervated cell clusters that express voltage-activated currents and function as airway O(2) sensors. We investigated A-type K(+) currents in NEB cells using neonatal rabbit lung slice preparation. The whole cell K(+) current was slowly inactivating with activation threshold of approximately -30 mV. This current was blocked approximately 27% by blood-depressing substance I (BDS-I; 3 microM), a selective blocker of Kv3.4 subunit, and reduced approximately 20% by tetraethylammonium (TEA; 100 microM). The BDS-I-sensitive component had an average peak value of 189 +/- 14 pA and showed fast inactivation kinetics that could be fitted by one-component exponential function with a time constant of (tau1) 77 +/- 10 ms. This Kv slowly inactivating current was also blocked by heteropodatoxin-2 (HpTx-2; 0.2 microM), a blocker of Kv4 subunit. The HpTx-2-sensitive current had an average peak value of 234 +/- 23 pA with a time constant (tau) 82 +/- 11 ms. Hypoxia (Po(2) = 15-20 mmHg) inhibited the slowly inactivating K(+) current by approximately 47%, during voltage steps from -30 to +30 mV, and no further inhibition occurred when TEA was combined with hypoxia. Nicotine at concentrations of 50 and 100 microM suppressed the slowly inactivating K(+) current by approximately 24 and approximately 40%, respectively. This suppression was not reversed by mecamylamine suggesting a direct effect of nicotine on these K(+) channels. In situ hybridization experiments detected expression of mRNAs for Kv3.4 and Kv4.3 subunits, while double-label immunofluorescence confirmed membrane localization of respective channel proteins in NEB cells. These studies suggest that the hypoxia-sensitive current in NEB cells is carried by slowly inactivating A-type K(+) channels, which underlie their oxygen-sensitive potassium currents, and that exposure to nicotine may directly affect their function, contributing to smoking-related lung disease.

Performance analysis of a potassium-base AMTEC cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, C.; Hendricks, T.J.; Hunt, T.K.

1998-07-01

Sodium-BASE Alkali-Metal-Thermal-to-Electric-Conversion (AMTEC) cells have been receiving increased attention and funding from the Department of Energy, NASA and the United States Air Force. Recently, sodium-BASE (Na-BASE) AMTEC cells were selected for the Advanced Radioisotope Power System (ARPS) program for the next generation of deep-space missions and spacecraft. Potassium-BASE (K-BASE) AMTEC cells have not received as much attention to date, even though the vapor pressure of potassium is higher than that of sodium at the same temperature. So that, K-BASE AMTEC cells with potentially higher open circuit voltage and higher power output than Na-BASE AMTEC cells are possible. Because the surfacemore » tension of potassium is about half of the surface tension of sodium at the same temperature, the artery and evaporator design in a potassium AMTEC cell has much more challenging pore size requirements than designs using sodium. This paper uses a flexible thermal/fluid/electrical model to predict the performance of a K-BASE AMTEC cell. Pore sizes in the artery of K-BASE AMTEC cells must be smaller by an order of magnitude than in Na-BASE AMTEC cells. The performance of a K-BASE AMTEC cell was higher than a Na-BASE AMTEC cell at low voltages/high currents. K-BASE AMTEC cells also have the potential of much better electrode performance, thereby creating another avenue for potentially better performance in K-BASE AMTEC cells.« less

Markers of bone resorption and calcium metabolism are related to dietary intake patterns in male and female bed rest subjects

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Zwart, S. R.; Hargens, A. r.

2006-01-01

Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (P<0.05). The ratio of dietary animal protein/potassium intake was not correlated with NTX before BR for males or females, but they were positively correlated in both groups of males during bed rest. Dietary animal protein/potassium and urine Ca were correlated before and during bed rest for the males, and only during bed rest for the females. Conversely, the ratio of dietary vegetable protein/potassium intake was negatively correlated with urinary calcium during bed rest for the females, but there was no relationship between vegetable protein/potassium intake and bone markers for the males. These data suggest that the ratio of animal protein/potassium intake may affect bone, particularly in bed rest subjects. These data show that the type of protein and gender may be additional factors that modulate the effect of diet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.

Regulation of /sup 3/H-dopamine release by presynaptic GABA and glutamate heteroreceptors in rat brain nucleus accumbens synaptosomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kovalev, G.I.; Hetey, L.

1987-06-01

The aim of this investigation was a neurochemical study of the effect of agonists of different types of GABA receptors - muscimol (type A receptor), baclofen (type B receptor), delta-aminolevulinic acid (DALA; GABA autoreceptor), and also of GABA itself - on tritium-labelled dopamine release, stimulated by potassium cations, from synaptosomes of the nuclei accumbenes of the rat brain.

The changes of potassium currents in RCS rat Müller cell during retinal degeneration.

PubMed

Zhao, TongTao; Li, YaoChen; Weng, ChuanHuang; Yin, ZhengQin

2012-01-03

Müller cells are the principal glial cells expressing membrane-bound potassium channel and predominantly mediating the homeostatic regulation of extracellular K+ produced by neuronal activity in retina. It's well known that Müller cells can be activated in many pathological conditions, but little is known about the change of potassium currents of Müller cells during the progression of retinitis pigmentosa. Herein, the Royal College of Surgeons rats (RCS rat) were employed to investigate some phenotypic and functional changes of Müller cells during retinal degeneration such as the expression of Kir4.1, membrane properties and K+ channel currents by using immunohistochemistry, RT-PCR, western blot and whole-cell patch clamping respectively. Compared with Müller cells in control retina, increased glutamine synthetase (GS) mRNA levels were seen at P30 and P60, and then decreased gradually in RCS rat retina. Morphologically, Müller cells showed significant hypertrophy and proliferation after p60. The increased expression of intermediate filament, glial fibrillary acidic protein (GFAP) and vimentin began at P30 and reached a peak at p60. Kir4.1 channels presented a peak expression at P30. Concomitantly, K(+) currents of Müller cells increased at P30 and decreased at P90 significantly. We concluded that retinal Müller cells of RCS rats underwent an activation initiated by the onset of retinal degeneration before p60 and then an obvious reactive gliosis, which led the basic membrane properties to suffer marked changes, and caused the Kir4.1 channels of Müller cells to occur a clear functional shift, even lose their normal electrophysiological properties. This process aggravates the impairment caused by the initial photoreceptor degeneration. Copyright © 2011 Elsevier B.V. All rights reserved.

Fine structures and ion images on fresh frozen dried ultrathin sections by transmission electron and scanning ion microscopy

NASA Astrophysics Data System (ADS)

Takaya, K.; Okabe, M.; Sawataishi, M.; Takashima, H.; Yoshida, T.

2003-01-01

Ion microscopy (IM) of air-dried or freeze-dried cryostat and semi-thin cryosections has provided ion images of elements and organic substances in wide areas of the tissue. For reproducible ion images by a shorter time of exposure to the primary ion beam, fresh frozen dried ultrathin sections were prepared by freezing the tissue in propane chilled with liquid nitrogen, cryocut at 60 nm, mounted on grids and silicon wafer pieces, and freeze-dried. Rat Cowper gland and sciatic nerve, bone marrow of the rat administered of lithium carbonate, tree frog and African toad spleen and buffy coat of atopic dermatitis patients were examined. Fine structures and ion images of the corresponding areas in the same or neighboring sections were observed by transmission electron microscopy (TEM) followed by sector type and time-of-flight type IM. Cells in the buffy coat contained larger amounts of potassium and magnesium while plasma had larger amounts of sodium and calcium. However, in the tissues, lithium, sodium, magnesium, calcium and potassium were distributed in the cell and calcium showed a granular appearance. A granular cell of the tree frog spleen contained sodium and potassium over the cell and magnesium and calcium were confined to granules.

Differences in morphology and sugar content of purple sweet potato (Ipomoea batatas L.) with potassium treatment at several altitudes

NASA Astrophysics Data System (ADS)

Sulistiani, R.; Rosmayati; Siregar, L. A. M.; Harahap, F.

2018-02-01

This research was conducted at three locations in low, medium and high plains. This study was aimed to determine the morphological changes and sugar content of sweet potato caused by potassium dose treatment and climate change. Data was analyzed by factorial randomized block design in time series with two factors. The first factor was Altitude: A1 (50 meter above sea level (MASL)), A2 (750 MASL) and A3 (1450 MASL). The second factor was Potassium: K0 (0 kg/ha), K1 (50 kg/ha), K2 (100 kg/ha) and K3 (150 kg/ha). The data of plant morphology change and sugar content was descriptively analized, while agronomic and harvest component data analysis by F test and continued with Duncan Multiple Range Test. The results of morphological observations showed different types of plant growth, which in the lowlands and medium plant growth types spread, twisted, more branches, wider leaf area. However, the plateau of plant growth was relatively dwarf, erect, no twist, huddled and short rods and small leaf area. The tuber weight per plant, number of tuber yield and tuber weight per plot in high altitude were significantly higher than lowland and medium. Similarly, increased altitude will be increased the sugar content significantly.

Risk-assessment and risk-taking behavior predict potassium- and amphetamine-induced dopamine response in the dorsal striatum of rats

PubMed Central

Palm, Sara; Momeni, Shima; Lundberg, Stina; Nylander, Ingrid; Roman, Erika

2014-01-01

Certain personality types and behavioral traits display high correlations to drug use and an increased level of dopamine in the reward system is a common denominator of all drugs of abuse. Dopamine response to drugs has been suggested to correlate with some of these personality types and to be a key factor influencing the predisposition to addiction. This study investigated if behavioral traits can be related to potassium- and amphetamine-induced dopamine response in the dorsal striatum, an area hypothesized to be involved in the shift from drug use to addiction. The open field and multivariate concentric square field™ tests were used to assess individual behavior in male Wistar rats. Chronoamperometric recordings were then made to study the potassium- and amphetamine-induced dopamine response in vivo. A classification based on risk-taking behavior in the open field was used for further comparisons. Risk-taking behavior was correlated between the behavioral tests and high risk takers displayed a more pronounced response to the dopamine uptake blocking effects of amphetamine. Behavioral parameters from both tests could also predict potassium- and amphetamine-induced dopamine responses showing a correlation between neurochemistry and behavior in risk-assessment and risk-taking parameters. In conclusion, the high risk-taking rats showed a more pronounced reduction of dopamine uptake in the dorsal striatum after amphetamine indicating that this area may contribute to the sensitivity of these animals to psychostimulants and proneness to addiction. Further, inherent dopamine activity was related to risk-assessment behavior, which may be of importance for decision-making and inhibitory control, key components in addiction. PMID:25076877

Combined effects of climate, restoration measures and slope position in change in soil chemical properties and nutrient loss across lands affected by the Wenchuan Earthquake in China.

PubMed

Lin, Yongming; Deng, Haojun; Du, Kun; Rafay, Loretta; Zhang, Guang-Shuai; Li, Jian; Chen, Can; Wu, Chengzhen; Lin, Han; Yu, Wei; Fan, Hailan; Ge, Yonggang

2017-10-15

The MS 8.0Wenchuan Earthquake in 2008 caused huge damage to land cover in the northwest of China's Sichuan province. In order to determine the nutrient loss and short term characteristics of change in soil chemical properties, we established an experiment with three treatments ('undestroyed', 'destroyed and treated', and 'destroyed and untreated'), two climate types (semi-arid hot climate and subtropical monsoon climate), and three slope positions (upslope, mid-slope, and bottom-slope) in 2011. Ten soil properties-including pH, organic carbon, total nitrogen, total phosphorus, total potassium, Ca 2+ , Mg 2+ , alkaline hydrolysable nitrogen, available phosphorus, and available potassium-were measured in surface soil samples in December 2014. Analyses were performed to compare the characteristics of 3-year change in soil chemical properties in two climate zones. This study revealed that soil organic carbon, total nitrogen, Ca 2+ content, alkaline hydrolysable nitrogen, available phosphorus, and available potassium were significantly higher in subtropical monsoon climate zones than in semi-arid hot climate zones. However, subtropical monsoon climate zones had a higher decrease in soil organic carbon, total nitrogen, total phosphorus, total potassium, and alkaline hydrolysable nitrogen in 'destroyed and untreated' sites than in semi-arid hot climate zones. Most soil chemical properties exhibited significant interactions, indicating that they may degrade or develop concomitantly. 'Destroyed and treated' sites in both climate types had lower C:P and N:P ratios than 'destroyed and untreated' sites. Principal component analysis (PCA) showed that the first, second, and third principal components explained 76.53% of the variation and might be interpreted as structural integrity, nutrient supply availability, and efficiency of soil; the difference of soil parent material; as well as weathering and leaching effects. Our study indicated that the characteristics of short term change in soil properties were affected by climate types and treatments, but not slope positions. Our results provide useful information for the selection of restoration countermeasures in different climate types to facilitate ecological restoration and reconstruction strategies in earthquake-affected areas. Copyright © 2017 Elsevier B.V. All rights reserved.

A Comparison of Concentrations of Sodium and Related Nutrients (Potassium, Total Dietary Fiber, Total and Saturated Fat, and Total Sugar) in Private-Label and National Brands of Popular, Sodium-Contributing, Commercially Packaged Foods in the United States.

PubMed

Ahuja, Jaspreet K C; Pehrsson, Pamela R; Cogswell, Mary

2017-05-01

Private-label brands account for about one in four foods sold in US supermarkets. They provide value to consumers due to their low cost. We know of no US studies comparing the nutrition content of private-label products with corresponding national brand products. The objective was to compare concentrations of sodium and related nutrients (potassium, total dietary fiber, total and saturated fat, and total sugar) in popular sodium-contributing, commercially packaged foods by brand type (national or private-label brand). During 2010 to 2014, the Nutrient Data Laboratory of the US Department of Agriculture obtained 1,706 samples of private-label and national brand products from up to 12 locations nationwide and chemically analyzed 937 composites for sodium and related nutrients. The samples came from 61 sodium-contributing, commercially packaged food products for which both private-label and national brands were among the top 75% to 80% of brands for US unit sales. In this post hoc comparative analysis, the authors assigned a variable brand type (national or private label) to each composite and determined mean nutrient contents by brand type overall and by food product and type. The authors tested for significant differences (P<0.05) by brand type using independent sample t tests or Mann-Whitney U tests when appropriate. Overall for all foods sampled, differences between brand types were not statistically significant for any of the nutrients studied. However, differences in both directions exist for a few individual food products and food categories. Concentrations of sodium and related nutrients (potassium, total dietary fiber, total and saturated fat, and total sugar) do not differ systematically between private-label and national brands, suggesting that brand type is not a consideration for nutritional quality of foods in the United States. The study data provide public health officials with baseline nutrient content by brand type to help focus US sodium-reduction efforts. Published by Elsevier Inc.

Reciprocal Modulation of IK1–INa Extends Excitability in Cardiac Ventricular Cells

PubMed Central

Varghese, Anthony

2016-01-01

The inwardly rectifying potassium current (IK1) and the fast inward sodium current (INa) are reciprocally modulated in mammalian ventricular myocytes. An increase in the expression of channels responsible for one of these two currents results in a corresponding increase in expression of the other. These currents are critical in the propagation of action potentials (AP) during the normal functioning of the heart. This study identifies a physiological role for IK1–INa reciprocal modulation in ventricular fiber activation thresholds and conduction. Simulations of action potentials in single cells and propagating APs in cardiac fibers were carried out using an existing model of electrical activity in cardiac ventricular myocytes. The conductances, GK1, of the inwardly rectifying potassium current, and GNa, of the fast inward sodium current were modified independently and in tandem to simulate reciprocal modulation. In single cells, independent modulation of GK1 alone resulted in changes in activation thresholds that were qualitatively similar to those for reciprocal GK1–GNa modulation and unlike those due to independent modulation of GNa alone, indicating that GK1 determines the cellular activation threshold. On the other hand, the variations in conduction velocity in cardiac cell fibers were similar for independent GNa modulation and for tandem changes in GK1–GNa, suggesting that GNa is primarily responsible for setting tissue AP conduction velocity. Conduction velocity dependence on GK1–GNa is significantly affected by the intercellular gap junction conductance. While the effects on the passive fiber space constant due to changes in both GK1 and the intercellular gap junction conductance, Ggj, were in line with linear cable theory predictions, both conductances had surprisingly large effects on fiber activation thresholds. Independent modulation of GK1 rendered cardiac fibers inexcitable at higher levels of GK1 whereas tandem GK1–GNa changes allowed fibers to remain excitable at high GK1 values. Reciprocal modulation of the inwardly rectifying potassium current and the fast inward sodium current may have a functional role in allowing cardiac tissue to remain excitable when IK1 is upregulated. PMID:27895596

Mechanism of potassium ion uptake by the Na+/K+-ATPase

PubMed Central

Castillo, Juan P.; Rui, Huan; Basilio, Daniel; Das, Avisek; Roux, Benoît; Latorre, Ramon; Bezanilla, Francisco; Holmgren, Miguel

2015-01-01

The Na+/K+-ATPase restores sodium (Na+) and potassium (K+) electrochemical gradients dissipated by action potentials and ion-coupled transport processes. As ions are transported, they become transiently trapped between intracellular and extracellular gates. Once the external gate opens, three Na+ ions are released, followed by the binding and occlusion of two K+ ions. While the mechanisms of Na+ release have been well characterized by the study of transient Na+ currents, smaller and faster transient currents mediated by external K+ have been more difficult to study. Here we show that external K+ ions travelling to their binding sites sense only a small fraction of the electric field as they rapidly and simultaneously become occluded. Consistent with these results, molecular dynamics simulations of a pump model show a wide water-filled access channel connecting the binding site to the external solution. These results suggest a mechanism of K+ gating different from that of Na+ occlusion. PMID:26205423

Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date

PubMed Central

Sugano, Kentaro

2018-01-01

Potassium-competitive acid blocker (P-CAB) is a class of drug that competitively blocks the potassium-binding site of H+, K+-adenosine triphosphate (ATP)ase. Although the history of this class of drugs started over 30 years ago, clinical use of two P-CABs, revaprazan and vonoprazan, were only recently approved in Korea and Japan, respectively. Among them, vonoprazan has several advantages over conventional proton-pump inhibitors (PPIs), including rapid onset of action, long duration of acid suppression, fewer interindividual variations in terms of acid suppression, and minimum dietary influence on its action. These advantages of vonoprazan have been proved in clinical trials conducted for license approvals for several acid-related diseases. In this review article, current evidence of vonoprazan in the management of gastroesophageal reflux disease (GERD) will be summarized. Since the clinical trial data, as well as postmarketed clinical data, have consistently demonstrated superiority of vonoprazan over conventional PPIs in terms of achieving healing of mucosal breaks and maintaining the healing, it may provide an excellent, if not complete, option for fulfilling some of the unmet needs for current GERD therapy. The safety problem of vonoprazan is also discussed, as more pronounced hypergastrinemia inevitably ensues with its use. PMID:29383028

Novel KCNQ3 Mutation in a Large Family with Benign Familial Neonatal Epilepsy: A Rare Cause of Neonatal Seizures

PubMed Central

Maljevic, Snezana; Vejzovic, Sabina; Bernhard, Matthias K.; Bertsche, Astrid; Weise, Sebastian; Döcker, Miriam; Lerche, Holger; Lemke, Johannes R.; Merkenschlager, Andreas; Syrbe, Steffen

2016-01-01

Benign familial neonatal seizures (BFNS) present a rare familial epilepsy syndrome caused by genetic alterations in the voltage-gated potassium channels Kv7.2 and Kv7.3, encoded by KCNQ2 and KCNQ3. While most BFNS families carry alterations in KCNQ2, mutations in KCNQ3 appear to be less common. Here, we describe a family with 6 individuals presenting with neonatal focal and generalized seizures. Genetic testing revealed a novel KCNQ3 variant, c.835G>T, cosegregating with seizures in 4 tested individuals. This variant results in a substitution of the highly conserved amino acid valine localized within the pore-forming transmembrane segment S5 (p.V279F). Functional investigations in Xenopus laevis oocytes revealed a loss of function, which supports p.V279F as a pathogenic mutation. When p.V279F was coexpressed with the wild-type (WT) Kv7.2 subunits, the resulting potassium currents were about 10-fold reduced compared to the WT Kv7.3 and Kv7.2 coexpression. Genotype-phenotype correlation shows an incomplete penetrance of p.V279F. Response to antiepileptic treatment was variable, but evaluation of treatment response remained challenging due to the self-limiting character of the disease. The identification of the pathogenic variant helped to avoid unnecessary investigations in affected family members and allowed guided therapy. PMID:27781029

Novel KCNQ3 Mutation in a Large Family with Benign Familial Neonatal Epilepsy: A Rare Cause of Neonatal Seizures.

PubMed

Maljevic, Snezana; Vejzovic, Sabina; Bernhard, Matthias K; Bertsche, Astrid; Weise, Sebastian; Döcker, Miriam; Lerche, Holger; Lemke, Johannes R; Merkenschlager, Andreas; Syrbe, Steffen

2016-09-01

Benign familial neonatal seizures (BFNS) present a rare familial epilepsy syndrome caused by genetic alterations in the voltage-gated potassium channels Kv7.2 and Kv7.3, encoded by KCNQ2 and KCNQ3. While most BFNS families carry alterations in KCNQ2 , mutations in KCNQ3 appear to be less common. Here, we describe a family with 6 individuals presenting with neonatal focal and generalized seizures. Genetic testing revealed a novel KCNQ3 variant, c.835G>T, cosegregating with seizures in 4 tested individuals. This variant results in a substitution of the highly conserved amino acid valine localized within the pore-forming transmembrane segment S5 (p.V279F). Functional investigations in Xenopus laevis oocytes revealed a loss of function, which supports p.V279F as a pathogenic mutation. When p.V279F was coexpressed with the wild-type (WT) Kv7.2 subunits, the resulting potassium currents were about 10-fold reduced compared to the WT Kv7.3 and Kv7.2 coexpression. Genotype-phenotype correlation shows an incomplete penetrance of p.V279F. Response to antiepileptic treatment was variable, but evaluation of treatment response remained challenging due to the self-limiting character of the disease. The identification of the pathogenic variant helped to avoid unnecessary investigations in affected family members and allowed guided therapy.

Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide.

PubMed

Sales, Thais Torquato; Resende, Fernando Francisco Borges; Chaves, Natália Lemos; Titze-De-Almeida, Simoneide Souza; Báo, Sônia Nair; Brettas, Marcella Lemos; Titze-De-Almeida, Ricardo

2016-10-01

Glioblastoma multiforme (GBM) is the most aggressive type of human primary brain tumor. The standard treatment protocol includes radiotherapy in combination with temozolomide (TMZ). Despite advances in GBM treatment, the survival time of patients diagnosed with glioma is 14.5 months. Regarding tumor biology, various types of cancer cell overexpress the ether à go-go 1 (Eag1) potassium channel. Therefore, the present study examined the role of Eag1 in the cell damage caused by TMZ on the U87MG glioblastoma cell line. Eag1 was inhibited using a channel blocker (astemizole) or silenced by a short-hairpin RNA expression vector (pKv10.1-3). pKv10.1-3 (0.2 µg) improved the Eag1 silencing caused by 250 µM TMZ, as determined by reverse transcription-quantitative polymerase chain reaction and immunocytochemistry. Additionally, inhibiting Eag1 with the vector or astemizole (5 µM) reduced glioblastoma cell viability and sensitized cells to TMZ. Cell viability decreased by 63% for pKv10.1-3 + TMZ compared with 34% for TMZ alone, and by 77% for astemizole + TMZ compared with 46% for TMZ alone, as determined by MTT assay. In addition, both the vector and astemizole increased the apoptosis rate of glioblastoma cells triggered by TMZ, as determined by an Annexin V apoptosis assay. Collectively, the current data reveal that Eag1 has a role in the damage caused to glioblastoma by TMZ. Furthermore, suppression of this channel can improve the action of TMZ on U87MG glioblastoma cells. Thus, silencing Eag1 is a promising strategy to improve GBM treatment and merits additional studies in animal models of glioma.

PhcrTx2, a New Crab-Paralyzing Peptide Toxin from the Sea Anemone Phymanthus crucifer

PubMed Central

Garateix, Anoland; Salceda, Emilio; Zaharenko, André Junqueira; Pons, Tirso; Santos, Yúlica; Arreguín, Roberto; Ständker, Ludger; Forssmann, Wolf-Georg; Tytgat, Jan; Vega, Rosario

2018-01-01

Sea anemones produce proteinaceous toxins for predation and defense, including peptide toxins that act on a large variety of ion channels of pharmacological and biomedical interest. Phymanthus crucifer is commonly found in the Caribbean Sea; however, the chemical structure and biological activity of its toxins remain unknown, with the exception of PhcrTx1, an acid-sensing ion channel (ASIC) inhibitor. Therefore, in the present work, we focused on the isolation and characterization of new P. crucifer toxins by chromatographic fractionation, followed by a toxicity screening on crabs, an evaluation of ion channels, and sequence analysis. Five groups of toxic chromatographic fractions were found, and a new paralyzing toxin was purified and named PhcrTx2. The toxin inhibited glutamate-gated currents in snail neurons (maximum inhibition of 35%, IC50 4.7 µM), and displayed little or no influence on voltage-sensitive sodium/potassium channels in snail and rat dorsal root ganglion (DRG) neurons, nor on a variety of cloned voltage-gated ion channels. The toxin sequence was fully elucidated by Edman degradation. PhcrTx2 is a new β-defensin-fold peptide that shares a sequence similarity to type 3 potassium channels toxins. However, its low activity on the evaluated ion channels suggests that its molecular target remains unknown. PhcrTx2 is the first known paralyzing toxin in the family Phymanthidae. PMID:29414882

A pharmacokinetic-pharmacodynamic model for the quantitative prediction of dofetilide clinical QT prolongation from human ether-a-go-go-related gene current inhibition data.

PubMed

Jonker, Daniël M; Kenna, Leslie A; Leishman, Derek; Wallis, Rob; Milligan, Peter A; Jonsson, E Niclas

2005-06-01

QT prolongation is an important biomarker of the arrhythmia torsades de pointes and appears to be related mainly to blockade of delayed inward cardiac rectifier potassium currents. The aim of this study was to quantify the relationship between in vitro human ether-a-go-go-related gene (hERG) potassium channel blockade and the magnitude of QT prolongation in humans for the class III antiarrhythmic dofetilide. The in vitro affinity and activity of dofetilide were determined in recombinant cell cultures expressing the hERG channel, and the QT-prolonging effect of dofetilide was assessed in 5 clinical studies (80 healthy volunteers and 17 patients with ischemic heart disease). A population pharmacokinetic-pharmacodynamic analysis of the in vitro and in vivo data was performed in NONMEM by use of the operational model of pharmacologic agonism to estimate the efficiency of transduction from ion channel binding to Fridericia-corrected QT response. A 3-compartment pharmacokinetic model with first-order absorption characterized the time course of dofetilide concentrations. On the basis of an in vitro potency of 5.13 ng/mL for potassium current inhibition and predicted unbound dofetilide concentrations, the estimated transducer ratio (tau) of 6.2 suggests that the QT response plateaus before currents are fully blocked. In our study population, 10% hERG blockade corresponds to a QT prolongation of 20 ms (95% confidence interval, 12-32 ms). With long-term dofetilide administration, tolerance develops with a half-life of 4.7 days. The current mechanism-based pharmacokinetic-pharmacodynamic model quantified the relationship between in vitro hERG channel blockade and clinical QT prolongation for dofetilide. This model may prove valuable for assessing the risk of QT prolongation in humans for other drugs that selectively block the hERG channel on the basis of in vitro assays and pharmacokinetic properties.

Voltage-Dependent Gating of hERG Potassium Channels

PubMed Central

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

Advances in the management of hyperkalemia in chronic kidney disease.

PubMed

Cowan, Andrea C J; Gharib, Elie G; Weir, Matthew A

2017-05-01

Patients with chronic kidney disease (CKD) have an increased risk of hyperkalemia that increases both short-term and long-term mortality. Historically, managing hyperkalemia has relied upon dietary modifications, augmentation of urinary potassium excretion and enhanced enteral potassium elimination. This review discusses current treatments and their limitations and summarizes the evidence supporting novel agents for potassium lowering in patients with CKD. The introduction of two novel ion exchange resins represents the first new pharmacologic therapies for hyperkalemia in the last 50 years. Patiromer, which was recently approved for use in the United States, has been shown to be well tolerated and effective for decreasing serum potassium in patients with CKD when taken for up to a year. Sodium zirconium cyclosilicate for which approval is pending has also shown promise in treating both acute and chronic hyperkalemia in patients with CKD. Both medications have been well tolerated with minimal adverse events in relatively short-term follow-up. Novel ion exchange resins have the potential to provide new strategies for safely and effectively managing hyperkalemia in the CKD population. This may decrease morbidity and mortality associated with hyperkalemia and allow more broad use of medications whose use is otherwise limited by hyperkalemia.

Revisiting RAAS blockade in CKD with newer potassium-binding drugs.

PubMed

Georgianos, Panagiotis I; Agarwal, Rajiv

2018-02-01

Among patients with proteinuric chronic kidney disease (CKD), current guideline recommendations mandate the use of agents blocking the renin angiotensin aldosterone system (RAAS) as first-line antihypertensive therapy based on randomized trials demonstrating that RAAS inhibitors are superior to other antihypertensive drug classes in slowing nephropathy progression to end-stage renal disease. However, the opportunities for adequate RAAS blockade in CKD are often limited, and an important impediment is the risk of hyperkalemia, especially when RAAS inhibitors are used in maximal doses or are combined. Accordingly, a large proportion of patients with proteinuric CKD may not have the anticipated renoprotective benefits since RAAS blockers are often discontinued due to incident hyperkalemia or are administered at suboptimal doses for fear of the development of hyperkalemia. Two newer potassium binders, patiromer and sodium zirconium cyclosilicate (ZS-9), have been shown to effectively and safely reduce serum potassium levels and maintain long-term normokalemia in CKD patients receiving background therapy with RAAS inhibitors. Whether these novel potassium-lowering therapies can overcome the barrier of hyperkalemia and enhance the tolerability of RAAS inhibitor use in proteinuric CKD awaits randomized trials. Published by Elsevier Inc.

Optomechanical design and analysis of a self-adaptive mounting method for optimizing phase matching of large potassium dihydrogen phosphate converter

NASA Astrophysics Data System (ADS)

Zhang, Zheng; Tian, Menjiya; Quan, Xusong; Pei, Guoqing; Wang, Hui; Liu, Tianye; Long, Kai; Xiong, Zhao; Rong, Yiming

2017-11-01

Surface control and phase matching of large laser conversion optics are urgent requirements and huge challenges in high-power solid-state laser facilities. A self-adaptive, nanocompensating mounting configuration of a large aperture potassium dihydrogen phosphate (KDP) frequency doubler is proposed based on a lever-type surface correction mechanism. A mechanical, numerical, and optical model is developed and employed to evaluate comprehensive performance of this mounting method. The results validate the method's advantages of surface adjustment and phase matching improvement. In addition, the optimal value of the modulation force is figured out through a series of simulations and calculations.

Single-particle characterization of biomass burning organic aerosol (BBOA): evidence for non-uniform mixing of high molecular weight organics and potassium

NASA Astrophysics Data System (ADS)

Lee, Alex K. Y.; Willis, Megan D.; Healy, Robert M.; Wang, Jon M.; Jeong, Cheol-Heon; Wenger, John C.; Evans, Greg J.; Abbatt, Jonathan P. D.

2016-05-01

Biomass burning organic aerosol (BBOA) can be emitted from natural forest fires and human activities such as agricultural burning and domestic energy generation. BBOA is strongly associated with atmospheric brown carbon (BrC) that absorbs near-ultraviolet and visible light, resulting in significant impacts on regional visibility degradation and radiative forcing. The mixing state of BBOA can play a critical role in the prediction of aerosol optical properties. In this work, single-particle measurements from a Soot-Particle Aerosol Mass Spectrometer coupled with a light scattering module (LS-SP-AMS) were performed to examine the mixing state of BBOA, refractory black carbon (rBC), and potassium (K, a tracer for biomass burning aerosol) in an air mass influenced by wildfire emissions transported from northern Québec to Toronto, representing aged biomass burning plumes. Cluster analysis of single-particle measurements identified five BBOA-related particle types. rBC accounted for 3-14 wt % of these particle types on average. Only one particle type exhibited a strong ion signal for K+, with mass spectra characterized by low molecular weight organic species. The remaining four particle types were classified based on the apparent molecular weight of the BBOA constituents. Two particle types were associated with low potassium content and significant amounts of high molecular weight (HMW) organic compounds. Our observations indicate non-uniform mixing of particles within a biomass burning plume in terms of molecular weight and illustrate that HMW BBOA can be a key contributor to low-volatility BrC observed in BBOA particles. The average mass absorption efficiency of low-volatility BBOA is about 0.8-1.1 m2 g-1 based on a theoretical closure calculation. Our estimates indicate that low-volatility BBOA contributes ˜ 33-44 % of thermo-processed particle absorption at 405 nm; and almost all of the BBOA absorption was associated with low-volatility organics.

Abiotic synthesis of fatty acids

NASA Technical Reports Server (NTRS)

Leach, W. W.; Nooner, D. W.; Oro, J.

1978-01-01

The formation of fatty acids by Fischer-Tropsch-type synthesis was investigated with ferric oxide, ammonium carbonate, potassium carbonate, powdered Pueblito de Allende carbonaceous chondrite, and filings from the Canyon Diablo meteorite used as catalysts. Products were separated and identified by gas chromatography and mass spectrometry. Iron oxide, Pueblito de Allende chondrite, and Canyon Diablo filings in an oxidized catalyst form yielded no fatty acids. Canyon Diablo filings heated overnight at 500 C while undergoing slow purging by deuterium produced fatty acids only when potassium carbonate was admixed; potassium carbonate alone also produced these compounds. The active catalytic combinations gave relatively high yields of aliphatic and aromatic hydrocarbons; substantial amounts of n-alkenes were almost invariably observed when fatty acids were produced; the latter were in the range C6 to C18, with maximum yield in C9 or 10.

Dissection of K+ currents in Caenorhabditis elegans muscle cells by genetics and RNA interference

PubMed Central

Santi, C. M.; Yuan, A.; Fawcett, G.; Wang, Z.-W.; Butler, A.; Nonet, M. L.; Wei, A.; Rojas, P.; Salkoff, L.

2003-01-01

GFP-promoter experiments have previously shown that at least nine genes encoding potassium channel subunits are expressed in Caenorhabditis elegans muscle. By using genetic, RNA interference, and physiological techniques we revealed the molecular identity of the major components of the outward K+ currents in body wall muscle cells in culture. We found that under physiological conditions, outward current is dominated by the products of only two genes, Shaker (Kv1) and Shal (Kv4), both expressing voltage-dependent potassium channels. Other channels may be held in reserve to respond to particular circumstances. Because GFP-promoter experiments indicated that slo-2 expression is prominent, we created a deletion mutant to identify the SLO-2 current in vivo. In both whole-cell and single-channel modes, in vivo SLO-2 channels were active only when intracellular Ca2+ and Cl- were raised above normal physiological conditions, as occurs during hypoxia. Under such conditions, SLO-2 is the largest outward current, contributing up to 87% of the total current. Other channels are present in muscle, but our results suggest that they are unlikely to contribute a large outward component under physiological conditions. However, they, too, may contribute currents conditional on other factors. Hence, the picture that emerges is of a complex membrane with a small number of household conductances functioning under normal circumstances, but with additional conductances that are activated during unusual circumstances. PMID:14612577

Neurovascular coupling protects neurons against hypoxic injury via inhibition of potassium currents by generation of nitric oxide in direct neuron and endothelium cocultures.

PubMed

Wu, Kun-Wei; Kou, Zeng-Wei; Mo, Jia-Lin; Deng, Xu-Xu; Sun, Feng-Yan

2016-10-15

This study examined the effect of neuron-endothelial coupling on the survival of neurons after ischemia and the possible mechanism underlying that effect. Whole-cell patch-clamp experiments were performed on cortical neurons cultured alone or directly cocultured with brain microvascular endothelial cells (BMEC). Propidium iodide (PI) and NeuN staining were performed to examine neuronal death following oxygen and glucose deprivation (OGD). We found that the neuronal transient outward potassium currents (I A ) decreased in the coculture system, whereas the outward delayed-rectifier potassium currents (I K ) did not. Sodium nitroprusside, a NO donor, enhanced BMEC-induced I A inhibition and nitro-l-arginine methylester, a NOS inhibitor, partially prevented this inhibition. Moreover, the neurons directly cocultured with BMEC showed more resistance to OGD-induced injury compared with the neurons cultured alone, and that neuroprotective effect was abolished by treatment with NS5806, an activator of the I A . These results indicate that vascular endothelial cells assist neurons to prevent hypoxic injury via inhibiting neuronal I A by production of NO in the direct neuron-BMEC coculture system. These results further provide direct evidence of functional coupling between neurons and vascular endothelial cells. This study clearly demonstrates that vascular endothelial cells play beneficial roles in the pathophysiological processes of neurons after hypoxic injury, suggesting that the improvement of neurovascular coupling or functional remodeling may become an important therapeutic target for preventing brain injury. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Geraniol blocks calcium and potassium channels in the mammalian myocardium: useful effects to treat arrhythmias.

PubMed

de Menezes-Filho, José Evaldo Rodrigues; Gondim, Antônio Nei Santana; Cruz, Jader Santos; de Souza, Américo Azevedo; Santos, José Nilson Andrade Dos; Conde-Garcia, Eduardo Antônio; de Sousa, Damião Pergentino; Santos, Michel Santana; de Oliveira, Evaleide Diniz; de Vasconcelos, Carla Maria Lins

2014-12-01

Geraniol is a monoterpene present in several essential oils, and it is known to have a plethora of pharmacological activities. In this study, we explored the contractile and electrophysiological properties of geraniol and its antiarrhythmic effects in the heart. The geraniol effects on atrial contractility, L-type Ca(2+) current, K(+) currents, action potential (AP) parameters, ECG profile and on the arrhythmia induced by ouabain were evaluated. In the atrium, geraniol reduced the contractile force (~98%, EC = 1,510 ± 160 μM) and diminished the positive inotropism of CaCl2 and BAY K8644. In cardiomyocytes, the IC a,L was reduced by 50.7% (n = 5) after perfusion with 300 μM geraniol. Moreover, geraniol prolonged the AP duration (APD) measured at 50% (n = 5) after repolarization, without changing the resting potential. The increased APD could be attributed to the blockade of the transient outward K(+) current (Ito ) (59.7%, n = 4), the non-inactivation K(+) current (Iss ) (39.2%, n = 4) and the inward rectifier K(+) current (IK 1 ) (33.7%, n = 4). In isolated hearts, geraniol increased PRi and QTi without affecting the QRS complex (n = 6), and it reduced both the left ventricular pressure (83%) and heart rate (16.5%). Geraniol delayed the time to onset of ouabain-induced arrhythmias by 128%, preventing 30% of the increase in resting tension (n = 6). Geraniol exerts its negative inotropic and chronotropic responses in the heart by decreasing both L-type Ca(2+) and voltage-gated K(+) currents, ultimately acting against ouabain-induced arrhythmias. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

New Molecular Targets for Antiepileptic Drugs: α2δ, SV2A, and Kv7/KCNQ/M Potassium Channels

PubMed Central

Rogawski, Michael A.; Bazil, Carl W.

2008-01-01

Many currently prescribed antiepileptic drugs (AEDs) act via voltage-gated sodium channels, through effects on γ-aminobutyric acid–mediated inhibition, or via voltage-gated calcium channels. Some newer AEDs do not act via these traditional mechanisms. The molecular targets for several of these nontraditional AEDs have been defined using cellular electrophysiology and molecular approaches. Here, we describe three of these targets: α2δ, auxiliary subunits of voltage-gated calcium channels through which the gabapentinoids gabapentin and pregabalin exert their anticonvulsant and analgesic actions; SV2A, a ubiquitous synaptic vesicle glycoprotein that may prepare vesicles for fusion and serves as the target for levetiracetam and its analog brivaracetam (which is currently in late-stage clinical development); and Kv7/KCNQ/M potassium channels that mediate the M-current, which acts a brake on repetitive firing and burst generation and serves as the target for the investigational AEDs retigabine and ICA-105665. Functionally, all of the new targets modulate neurotransmitter output at synapses, focusing attention on presynaptic terminals as critical sites of action for AEDs. PMID:18590620

New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels.

PubMed

Rogawski, Michael A; Bazil, Carl W

2008-07-01

Many currently prescribed antiepileptic drugs (AEDs) act via voltage-gated sodium channels, through effects on gamma-aminobutyric acid-mediated inhibition, or via voltage-gated calcium channels. Some newer AEDs do not act via these traditional mechanisms. The molecular targets for several of these nontraditional AEDs have been defined using cellular electrophysiology and molecular approaches. Here, we describe three of these targets: alpha(2)delta, auxiliary subunits of voltage-gated calcium channels through which the gabapentinoids gabapentin and pregabalin exert their anticonvulsant and analgesic actions; SV2A, a ubiquitous synaptic vesicle glycoprotein that may prepare vesicles for fusion and serves as the target for levetiracetam and its analog brivaracetam (which is currently in late-stage clinical development); and K(v)7/KCNQ/M potassium channels that mediate the M-current, which acts a brake on repetitive firing and burst generation and serves as the target for the investigational AEDs retigabine and ICA-105665. Functionally, all of the new targets modulate neurotransmitter output at synapses, focusing attention on presynaptic terminals as critical sites of action for AEDs.

Investigation of the Prussian Blue Analog Co3 [Co(CN)6 ]2 as an Anode Material for Nonaqueous Potassium-Ion Batteries.

PubMed

Deng, Leqing; Yang, Zhao; Tan, Lulu; Zeng, Liang; Zhu, Yujie; Guo, Lin

2018-06-21

Nonaqueous potassium-ion batteries (KIBs) are attracting increasing attention as a potential low-cost energy-storage system due to the abundance of potassium resources. Here, cobalt hexacyanocobaltate (Co 3 [Co(CN) 6 ] 2 ), a typical Prussian blue analog (PBA), is reported as an anode material for nonaqueous KIBs. The as-prepared Co 3 [Co(CN) 6 ] 2 exhibits a highly reversible capacity of 324.5 mAh g -1 at a current density of 0.1 A g -1 , a superior rate capability (221 mAh g -1 at 1 A g -1 ), and a favorable long-term cycling stability (200 cycles with 82% capacity retention). Based on a series of characterizations, it is found that potassiation/depotassiation in Co 3 [Co(CN) 6 ] 2 proceeds via solid-state diffusion-limited K-ion insertion/extraction process, in which both carbon- and nitrogen-coordinated cobalt are electrochemically active toward K-ion storage. Finally, the reaction pathway between potassium and Co 3 [Co(CN) 6 ] 2 is proposed. The present study provides new insights on further exploration of PBAs as high-performance electrode materials for KIBs. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia

PubMed Central

Irani, Sarosh R.; Alexander, Sian; Waters, Patrick; Kleopa, Kleopas A.; Pettingill, Philippa; Zuliani, Luigi; Peles, Elior; Buckley, Camilla; Lang, Bethan

2010-01-01

Antibodies that immunoprecipitate 125I-α-dendrotoxin-labelled voltage-gated potassium channels extracted from mammalian brain tissue have been identified in patients with neuromyotonia, Morvan’s syndrome, limbic encephalitis and a few cases of adult-onset epilepsy. These conditions often improve following immunomodulatory therapies. However, the proportions of the different syndromes, the numbers with associated tumours and the relationships with potassium channel subunit antibody specificities have been unclear. We documented the clinical phenotype and tumour associations in 96 potassium channel antibody positive patients (titres >400 pM). Five had thymomas and one had an endometrial adenocarcinoma. To define the antibody specificities, we looked for binding of serum antibodies and their effects on potassium channel currents using human embryonic kidney cells expressing the potassium channel subunits. Surprisingly, only three of the patients had antibodies directed against the potassium channel subunits. By contrast, we found antibodies to three proteins that are complexed with 125I-α-dendrotoxin-labelled potassium channels in brain extracts: (i) contactin-associated protein-2 that is localized at the juxtaparanodes in myelinated axons; (ii) leucine-rich, glioma inactivated 1 protein that is most strongly expressed in the hippocampus; and (iii) Tag-1/contactin-2 that associates with contactin-associated protein-2. Antibodies to Kv1 subunits were found in three sera, to contactin-associated protein-2 in 19 sera, to leucine-rich, glioma inactivated 1 protein in 55 sera and to contactin-2 in five sera, four of which were also positive for the other antibodies. The remaining 18 sera were negative for potassium channel subunits and associated proteins by the methods employed. Of the 19 patients with contactin-associated protein-antibody-2, 10 had neuromyotonia or Morvan’s syndrome, compared with only 3 of the 55 leucine-rich, glioma inactivated 1 protein-antibody positive patients (P < 0.0001), who predominantly had limbic encephalitis. The responses to immunomodulatory therapies, defined by changes in modified Rankin scores, were good except in the patients with tumours, who all had contactin-associated-2 protein antibodies. This study confirms that the majority of patients with high potassium channel antibodies have limbic encephalitis without tumours. The identification of leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 as the major targets of potassium channel antibodies, and their associations with different clinical features, begins to explain the diversity of these syndromes; furthermore, detection of contactin-associated protein-2 antibodies should help identify the risk of an underlying tumour and a poor prognosis in future patients. PMID:20663977

Amorphous cobalt potassium phosphate microclusters as efficient photoelectrochemical water oxidation catalyst

NASA Astrophysics Data System (ADS)

Zhang, Ye; Zhao, Chunsong; Dai, Xuezeng; Lin, Hong; Cui, Bai; Li, Jianbao

2013-12-01

A novel amorphous cobalt potassium phosphate hydrate compound (KCoPO4·H2O) is identified to be active photocatalyst for oxygen evolution reaction (OER) to facilitate hydrogen generation from water photolysis. It has been synthesized through a facile and cost-effective solution-based precipitation method using earth-abundant materials. Its highly porous structure and large surface areas are found to be responsible for the excellent electrochemical performance featuring a low OER onset at ∼550 mVSCE and high current density in alkaline condition. Unlike traditional cobalt-based spinel oxides (Co3O4, NiCo2O4) and phosphate (Co-Pi, Co(PO3)2) electrocatalysts, with proper energy band alignment for light-assisted water oxidation, cobalt potassium phosphate hydrate also exhibits robust visible-light response, generating a photocurrent density of ∼200 μA cm-2 at 0.7 VSCE. This catalyst could thus be considered as a promising candidate to perform photoelectrochemical water splitting.

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

PubMed

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.

Noble Gas Xenon Is a Novel Adenosine Triphosphate-sensitive Potassium Channel Opener

PubMed Central

Bantel, Carsten; Maze, Mervyn; Trapp, Stefan

2010-01-01

Background Adenosine triphosphate-sensitive potassium (KATP) channels in brain are involved in neuroprotective mechanisms. Pharmacologic activation of these channels is seen as beneficial, but clinical exploitation by using classic K+ channel openers is hampered by their inability to cross the blood–brain barrier. This is different with the inhalational anesthetic xenon, which recently has been suggested to activate KATP channels; it partitions freely into the brain. Methods To evaluate the type and mechanism of interaction of xenon with neuronal-type KATP channels, these channels, consisting of Kir6.2 pore-forming subunits and sulfonylurea receptor-1 regulatory subunits, were expressed in HEK293 cells and whole cell, and excised patch-clamp recordings were performed. Results Xenon, in contrast to classic KATP channel openers, acted directly on the Kir6.2 subunit of the channel. It had no effect on the closely related, adenosine triphosphate (ATP)-regulated Kir1.1 channel and failed to activate an ATP-insensitive mutant version of Kir6.2. Furthermore, concentration–inhibition curves for ATP obtained from inside-out patches in the absence or presence of 80% xenon revealed that xenon reduced the sensitivity of the KATP channel to ATP. This was reflected in an approximately fourfold shift of the concentration causing half-maximal inhibition (IC50) from 26 ± 4 to 96 ± 6 μm. Conclusions Xenon represents a novel KATP channel opener that increases KATP currents independently of the sulfonylurea receptor-1 subunit by reducing ATP inhibition of the channel. Through this action and by its ability to readily partition across the blood–brain barrier, xenon has considerable potential in clinical settings of neuronal injury, including stroke. PMID:20179498

Etelcalcetide Injection

MedlinePlus

... gradually) who are being treated with dialysis (medical treatment to clean the blood when the kidneys are ... of potassium or magnesium in the blood, seizures, stomach ulcers, any type of irritation or swelling of the ...

A Study of Early Afterdepolarizations in a Model for Human Ventricular Tissue

PubMed Central

Vandersickel, Nele; Kazbanov, Ivan V.; Nuitermans, Anita; Weise, Louis D.; Pandit, Rahul; Panfilov, Alexander V.

2014-01-01

Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium. PMID:24427289

Numerical simulation of submicron particles formation by condensation at coals burning

NASA Astrophysics Data System (ADS)

Kortsenshteyn, N. M.; Petrov, L. V.

2017-11-01

The thermodynamic analysis of the composition of the combustion products of 15 types of coals was carried out with consideration for the formation of potassium and sodium aluminosilicates and solid and liquid slag removal. Based on the results of the analysis, the approximating temperature dependences of the concentrations of condensed components (potassium and sodium sulfates) were obtained for the cases of two-phase and single-phase equilibriums; conclusions on the comparative influence of solid and liquid slag removal on the probability of the formation of submicron particles on the combustion of coals were made. The found dependences was make it possible to perform a numerical simulation of the bulk condensation of potassium and sodium sulfate vapors upon the cooling of coal combustion products in a process flow. The number concentration and size distribution of the formed particles have been determined. Agreement with experimental data on the fraction composition of particles has been reached at a reasonable value of a free parameter of the model.

Expression and Stress-Dependent Induction of Potassium Channel Transcripts in the Common Ice Plant1

PubMed Central

Su, Hua; Golldack, Dortje; Katsuhara, Maki; Zhao, Chengsong; Bohnert, Hans J.

2001-01-01

We have characterized transcripts for three potassium channel homologs in the AKT/KAT subfamily (Shaker type) from the common ice plant (Mesembryanthemum crystallinum), with a focus on their expression during salt stress (up to 500 mm NaCl). Mkt1 and 2, Arabidopsis AKT homologs, and Kmt1, a KAT homolog, are members of small gene families with two to three isoforms each. Mkt1 is root specific; Mkt2 is found in leaves, flowers, and seed capsules; and Kmt1 is expressed in leaves and seed capsules. Mkt1 is present in all cells of the root, and in leaves a highly conserved isoform is detected present in all cells with highest abundance in the vasculature. MKT1 for which antibodies were made is localized to the plasma membrane. Following salt stress, MKT1 (transcripts and protein) is drastically down-regulated, Mkt2 transcripts do not change significantly, and Kmt1 is strongly and transiently (maximum at 6 h) up-regulated in leaves and stems. The detection and stress-dependent behavior of abundant transcripts representing subfamilies of potassium channels provides information about tissue specificity and the complex regulation of genes encoding potassium uptake systems in a halophytic plant. PMID:11161018

Ammonia triggers neuronal disinhibition and seizures by impairing astrocyte potassium buffering

PubMed Central

Thrane, Vinita Rangroo; Thrane, Alexander S; Wang, Fushun; Cotrina, Maria L; Smith, Nathan A; Chen, Michael; Xu, Qiwu; Kang, Ning; Fujita, Takumi; Nagelhus, Erlend A; Nedergaard, Maiken

2013-01-01

Ammonia is a ubiquitous waste product of protein metabolism that can accumulate in numerous metabolic disorders, causing neurological dysfunction ranging from cognitive impairment to tremor, ataxia, seizures, coma and death1. The brain is especially vulnerable to ammonia as it readily crosses the blood-brain barrier in its gaseous form, NH3, and rapidly saturates its principal removal pathway located in astrocytes2. Thus, we wanted to determine how astrocytes contribute to the initial deterioration of neurological functions characteristic of hyperammonemia in vivo. Using a combination of two-photon imaging and electrophysiology in awake head-restrained mice, we show that ammonia rapidly compromises astrocyte potassium buffering, increasing extracellular potassium concentration and overactivating the Na+-K+-2Cl− cotransporter isoform 1 (NKCC1) in neurons. The consequent depolarization of the neuronal GABA reversal potential (EGABA) selectively impairs cortical inhibitory networks. Genetic deletion of NKCC1 or inhibition of it with the clinically used diuretic bumetanide potently suppresses ammonia-induced neurological dysfunction. We did not observe astrocyte swelling or brain edema in the acute phase, calling into question current concepts regarding the neurotoxic effects of ammonia3,4. Instead, our findings identify failure of potassium buffering in astrocytes as a crucial mechanism in ammonia neurotoxicity and demonstrate the therapeutic potential of blocking this pathway by inhibiting NKCC1. PMID:24240184

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

PubMed Central

Frolova, Sheyda R.; Gaiko, Olga; Tsvelaya, Valeriya A.; Pimenov, Oleg Y.; Agladze, Konstantin I.

2016-01-01

The ability of azobenzene trimethylammonium bromide (azoTAB) to sensitize cardiac tissue excitability to light was recently reported. The dark, thermally relaxed trans- isomer of azoTAB suppressed spontaneous activity and excitation propagation speed, whereas the cis- isomer had no detectable effect on the electrical properties of cardiomyocyte monolayers. As the membrane potential of cardiac cells is mainly controlled by activity of voltage-gated ion channels, this study examined whether the sensitization effect of azoTAB was exerted primarily via the modulation of voltage-gated ion channel activity. The effects of trans- and cis- isomers of azoTAB on voltage-dependent sodium (INav), calcium (ICav), and potassium (IKv) currents in isolated neonatal rat cardiomyocytes were investigated using the whole-cell patch-clamp technique. The experiments showed that azoTAB modulated ion currents, causing suppression of sodium (Na+) and calcium (Ca2+) currents and potentiation of net potassium (K+) currents. This finding confirms that azoTAB-effect on cardiac tissue excitability do indeed result from modulation of voltage-gated ion channels responsible for action potential. PMID:27015602

Effect of Functional Bread Rich in Potassium, γ-Aminobutyric Acid and Angiotensin-Converting Enzyme Inhibitors on Blood Pressure, Glucose Metabolism and Endothelial Function

PubMed Central

Becerra-Tomás, Nerea; Guasch-Ferré, Marta; Quilez, Joan; Merino, Jordi; Ferré, Raimon; Díaz-López, Andrés; Bulló, Mònica; Hernández-Alonso, Pablo; Palau-Galindo, Antoni; Salas-Salvadó, Jordi

2015-01-01

Abstract Because it has been suggested that food rich in γ-aminobutyric acid (GABA) or angiotensin-converting enzyme inhibitor (ACEI) peptides have beneficial effects on blood pressure (BP) and other cardiovascular risk factors, we tested the effects of low-sodium bread, but rich in potassium, GABA, and ACEI peptides on 24-hour BP, glucose metabolism, and endothelial function. A randomized, double-blind, crossover trial was conducted in 30 patients with pre or mild-to-moderate hypertension, comparing three 4-week nutritional interventions separated by 2-week washout periods. Patients were randomly assigned to consume 120 g/day of 1 of the 3 types of bread for each nutritional intervention: conventional wheat bread (CB), low-sodium wheat bread enriched in potassium (LSB), and low-sodium wheat bread rich in potassium, GABA, and ACEI peptides (LSB + G). For each period, 24-hour BP measurements, in vivo endothelial function, and biochemical samples were obtained. After LSB + G consumption, 24-hour ambulatory BP underwent a nonsignificant greater reduction than after the consumption of CB and LSB (0.26 mm Hg in systolic BP and −0.63 mm Hg in diastolic BP for CB; −0.71 mm Hg in systolic BP and −1.08 mm Hg in diastolic BP for LSB; and −0.75 mm Hg in systolic BP and −2.12 mm Hg in diastolic BP for LSB + G, respectively). Diastolic BP at rest decreased significantly during the LSB + G intervention, although there were no significant differences in changes between interventions. There were no significant differences between interventions in terms of changes in in vivo endothelial function, glucose metabolism, and peripheral inflammatory parameters. Compared with the consumption of CB or LSB, no greater beneficial effects on 24-hour BP, endothelial function, or glucose metabolism were demonstrated after the consumption of LSB + G in a population with pre or mild-to-moderate hypertension. Further studies are warranted to clarify the effect of GABA on BP, preferably using a specific design for noninferiority trials and ambulatory BP monitoring as a measure of BP. This study was registered at Current Controlled Trials as ISRCTN31436822 PMID:26579797

Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

NASA Technical Reports Server (NTRS)

Jorgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne; Civitelli, Roberto; Sorensen, Ole Helmer; Steinberg, Thomas H.

2003-01-01

The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal of extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx43 (UMR/Cx43) we confirmed that nifedipine sensitivity of ICW required Cx43 expression. In human osteoblastic cells, gap junction-dependent ICW also required activation of L-type calcium channels and influx of extracellular calcium.

Inwardly rectifying potassium channels influence Drosophila wing morphogenesis by regulating Dpp release.

PubMed

Dahal, Giri Raj; Pradhan, Sarala Joshi; Bates, Emily Anne

2017-08-01

Loss of embryonic ion channel function leads to morphological defects, but the underlying reason for these defects remains elusive. Here, we show that inwardly rectifying potassium (Irk) channels regulate release of the Drosophila bone morphogenetic protein Dpp in the developing fly wing and that this is necessary for developmental signaling. Inhibition of Irk channels decreases the incidence of distinct Dpp-GFP release events above baseline fluorescence while leading to a broader distribution of Dpp-GFP. Work by others in different cell types has shown that Irk channels regulate peptide release by modulating membrane potential and calcium levels. We found calcium transients in the developing wing, and inhibition of Irk channels reduces the duration and amplitude of calcium transients. Depolarization with high extracellular potassium evokes Dpp release. Taken together, our data implicate Irk channels as a requirement for regulated release of Dpp, highlighting the importance of the temporal pattern of Dpp presentation for morphogenesis of the wing. © 2017. Published by The Company of Biologists Ltd.

Selective suppression of the slow-inactivating potassium currents by nootropics in molluscan neurons.

PubMed

Bukanova, Julia V; Solntseva, Elena I; Skrebitsky, Vladimir G

2002-09-01

The role of the voltage-gated K+ channels in the effect of some nootropics was investigated. Earlier, the multiple effect of high concentrations of two nootropics, piracetam and its peptide analogue GVS-111 [Seredenin et al. (1995), US Patent No. 5,439,930], on Ca2+ and K+ currents of molluscan neurons was shown [Solntseva et al. (1997), General Pharmacology 29, 85-89]. In the present work, we describe the selective effect of low concentrations of these nootropics as well as vinpocetine on certain types of K+ current. The experiments were performed on isolated neurons of the land snail Helix pomatia using a two-microelectrode voltage-clamp method. The inward voltage-gated Ca2+ current (ICa) and three subtypes of the outward voltage-gated K+ current were recorded: Ca2+-dependent K+ current (IK(Ca)), delayed rectifying current (IKD), and fast-inactivating K+ current (IA). It has been found that I Ca was not changed in the presence of 30 microM vinpocetine, 100 microM piracetam or 10 nM GVS-111, while slow-inactivating, TEA-sensitive IK(Ca) and IKD were inhibited (IK(Ca) more strongly than IKD). In contrast, the fast-inactivating, 4-AP-sensitive K+ current (IA) was not diminished by low concentrations of piracetam and GVS-111, while vinpocetine even augmented it. A possible role of slow-inactivating subtypes of the K+ channels in the development of different forms of dementia is discussed.

Salivary flow and composition in diabetic and non-diabetic subjects.

PubMed

Lasisi, T J; Fasanmade, A A

2012-06-07

The study investigated the effects of type 2 diabetes mellitus on salivary flow and composition in humans compared to healthy sex and age matched controls. Forty adult human subjects divided into 20 diabetic and 20 non-diabetic healthy subjects were included. Saliva samples were collected and analysed for glucose, total protein, calcium, sodium, potassium, chloride and bicarbonate. Salivary flow rate was also determined. The results showed that salivary glucose and potassium levels were significantly higher (p = 0.01 and 0.002 respectively) in diabetic patients compared with non-diabetic participants. It was also found that the diabetic patients had significant reduction in salivary flow rate when compared with non-diabetic individuals. In contrast, there was no significant difference in levels of total protein, Na+, Ca++, Cl- and HCO3- between the two groups. These results suggest that some oral diseases associated with diabetes mellitus may be due to altered levels of salivary glucose, potassium and flow.

Mixing Acid Salts and Layered Double Hydroxides in Nanoscale under Solid Condition

PubMed Central

Nakayama, Hirokazu; Hayashi, Aki

2014-01-01

The immobilization of potassium sorbate, potassium aspartate and sorbic acid in layered double hydroxide under solid condition was examined. By simply mixing two solids, immobilization of sorbate and aspartate in the interlayer space of nitrate-type layered double hydroxide, so called intercalation reaction, was achieved, and the uptakes, that is, the amount of immobilized salts and the interlayer distances of intercalation compounds were almost the same as those obtained in aqueous solution. However, no intercalation was achieved for sorbic acid. Although intercalation of sorbate and aspartate into chloride-type layered double hydroxide was possible, the uptakes for these intercalation compounds were lower than those obtained using nitrate-type layered double hydroxide. The intercalation under solid condition could be achieved to the same extent as for ion-exchange reaction in aqueous solution, and the reactivity was similar to that observed in aqueous solution. This method will enable the encapsulation of acidic drug in layered double hydroxide as nano level simply by mixing both solids. PMID:25080007

Mixing Acid Salts and Layered Double Hydroxides in Nanoscale under Solid Condition.

PubMed

Nakayama, Hirokazu; Hayashi, Aki

2014-07-30

The immobilization of potassium sorbate, potassium aspartate and sorbic acid in layered double hydroxide under solid condition was examined. By simply mixing two solids, immobilization of sorbate and aspartate in the interlayer space of nitrate-type layered double hydroxide, so called intercalation reaction, was achieved, and the uptakes, that is, the amount of immobilized salts and the interlayer distances of intercalation compounds were almost the same as those obtained in aqueous solution. However, no intercalation was achieved for sorbic acid. Although intercalation of sorbate and aspartate into chloride-type layered double hydroxide was possible, the uptakes for these intercalation compounds were lower than those obtained using nitrate-type layered double hydroxide. The intercalation under solid condition could be achieved to the same extent as for ion-exchange reaction in aqueous solution, and the reactivity was similar to that observed in aqueous solution. This method will enable the encapsulation of acidic drug in layered double hydroxide as nano level simply by mixing both solids.

An experimental comparison between the continuum and single jump descriptions of nonactin-mediated potassium transport through black lipid membranes.

PubMed Central

van Dijk, C; de Levie, R

1985-01-01

The continuum and single jump treatments of ion transport through black lipid membranes predict experimentally distinguishable results, even when the same mechanistic assumptions are made and the same potential-distance profile is used. On the basis of steady-state current-voltage curves for nonactin-mediated transport of potassium ions, we find that the continuum model describes the data accurately, whereas the single jump model fails to do so, for all cases investigated in which capacitance measurements indicate that the membrane thickness varies little with applied potential. PMID:3839420

Preferential inhibition of Ih in rat trigeminal ganglion neurons by an organic blocker.

PubMed

Janigro, D; Martenson, M E; Baumann, T K

1997-11-15

The potency and specificity of a novel organic Ih current blocker DK-AH 268 (DK, Boehringer) was studied in cultured rat trigeminal ganglion neurons using whole-cell patch-clamp recording techniques. In neurons current-clamped at the resting potential, the application of 10 microM DK caused a slight hyperpolarization of the membrane potential and a small increase in the threshold for action potential discharge without any major change in the shape of the action potential. In voltage-clamped neurons, DK caused a reduction of a hyperpolarization-activated current. Current subtraction protocols revealed that the time-dependent, hyperpolarization-activated currents blocked by 10 microM DK or external Cs+ (3 mM) had virtually identical activation properties, suggesting that DK and Cs+ caused blockade of the same current, namely Ih. The block of Ih by DK was dose-dependent. At the intermediate and higher concentrations of DK (10 and 100 microM) a decrease in specificity was observed so that time-independent, inwardly rectifying and noninactivating, voltage-gated outward potassium currents were also reduced by DK but to a much lesser extent than the time-dependent, hyperpolarization-activated currents. Blockade of the time-dependent, hyperpolarization-activated currents by DK appeared to be use-dependent since it required hyperpolarization for the effect to take place. Relief of DK block was also aided by membrane hyperpolarization. Since both the time-dependent current blocked by DK and the Cs+-sensitive time-dependent current behaved as Ih, we conclude that 10 microM DK can preferentially reduce Ih without a major effect on other potassium currents. Thus, DK may be a useful agent in the investigation of the function of Ih in neurons.

Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout.

PubMed

Boscardin, Emilie; Perrier, Romain; Sergi, Chloé; Maillard, Marc P; Loffing, Johannes; Loffing-Cueni, Dominique; Koesters, Robert; Rossier, Bernard C; Hummler, Edith

2018-03-01

The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the α ENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of α ENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa + )/low potassium (LK + ) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γ ENaC subunit in the PHA-I phenotype. Nephron-specific γ ENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking α ENaC or β ΕΝaC, an HNa + /LK + diet did not normalize plasma potassium (K + ) concentration or increase NCC activation. However, when K + was eliminated from the diet at the time that γ ENaC was deleted, plasma K + concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced β ENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K + concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na + balance in γ ENaC-deficient mice. Copyright © 2018 by the American Society of Nephrology.

Oral potassium supplementation in surgical patients.

PubMed

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.

Achieving the Benefits of a High-Potassium, Paleolithic Diet, Without the Toxicity.

PubMed

Palmer, Biff F; Clegg, Deborah J

2016-04-01

The average US dietary intake of K(+) is well below the current recommended nutritional requirements. This deficiency is even more striking when comparing our current intake with that of our ancestors, who consumed large amounts of dietary K(+). K(+) deficiency has been implicated in many diseases including cardiovascular disease, kidney stones, and osteoporosis. Importantly, dietary supplementation of K(+) has favorable effects on reducing blood pressure, decreasing the risk of stroke, improving bone health, and reducing the risk of nephrolithiasis. For this comprehensive review, we scanned the literature using PubMed and MEDLINE using the following search terms: potassium intake, renal potassium excretion, and prevention of hyperkalemia. Articles were selected for inclusion if they represented primary data or review articles published between 1980 and 2015 in high-impact journals. The normal kidney has the capacity to tightly regulate K(+) homoeostasis. We discuss new findings with respect to sensing mechanisms by which the kidney maintains K(+) homeostasis in the gastrointestinal tract and distal tubule. There are widely prescribed hypertensive medications that cause hyperkalemia and thus require dietary K(+) restriction. We conclude by discussing newly approved drugs capable of binding K(+) in the gastrointestinal tract and speculate that this new pharmacology might allow diet liberalization in patients at risk for hyperkalemia, affording them the numerous benefits of a K(+)-rich diet. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Ionic mechanisms of action of prion protein fragment PrP(106-126) in rat basal forebrain neurons.

PubMed

Alier, Kwai; Li, Zongming; Mactavish, David; Westaway, David; Jhamandas, Jack H

2010-08-01

Prion diseases are neurodegenerative disorders that are characterized by the presence of the misfolded prion protein (PrP). Neurotoxicity in these diseases may result from prion-induced modulation of ion channel function, changes in neuronal excitability, and consequent disruption of cellular homeostasis. We therefore examined PrP effects on a suite of potassium (K(+)) conductances that govern excitability of basal forebrain neurons. Our study examined the effects of a PrP fragment [PrP(106-126), 50 nM] on rat neurons using the patch clamp technique. In this paradigm, PrP(106-126) peptide, but not the "scrambled" sequence of PrP(106-126), evoked a reduction of whole-cell outward currents in a voltage range between -30 and +30 mV. Reduction of whole-cell outward currents was significantly attenuated in Ca(2+)-free external media and also in the presence of iberiotoxin, a blocker of calcium-activated potassium conductance. PrP(106-126) application also evoked a depression of the delayed rectifier (I(K)) and transient outward (I(A)) potassium currents. By using single cell RT-PCR, we identified the presence of two neuronal chemical phenotypes, GABAergic and cholinergic, in cells from which we recorded. Furthermore, cholinergic and GABAergic neurons were shown to express K(v)4.2 channels. Our data establish that the central region of PrP, defined by the PrP(106-126) peptide used at nanomolar concentrations, induces a reduction of specific K(+) channel conductances in basal forebrain neurons. These findings suggest novel links between PrP signalling partners inferred from genetic experiments, K(+) channels, and PrP-mediated neurotoxicity.

Generation Mechanism of Alternans in Luo-Rudy Model

NASA Astrophysics Data System (ADS)

Kitajima, Hiroyuki; Ioka, Eri; Yazawa, Toru

Electrical alternans is the alternating amplitude from beat to beat in the action potential of the cardiac cell. It has been associated with ventricular arrhythmias in many clinical studies; however, its dynamical mechanisms remain unknown. The reason is that we do not have realistic network models of the heart system. Recently, Yazawa clarified the network structure of the heart and the central nerve system in the crustacean heart. In this study, we construct a simple model of the heart system based on Yazawa’s experimental data. Using this model, we clarify that two parameters (the conductance of sodium ions and free concentration of potassium ions in the extracellular compartment) play the key roles of generating alternans. In particular, we clarify that the inactivation gate of the time-independent potassium channel is the most important parameter. Moreover, interaction between the membrane potential and potassium ionic currents is significant for generating alternate rhythms. This result indicates that if the muscle cell has problems such as channelopathies, there is great risk of generating alternans.

[Spinocerebellar ataxias in infancy: pathogenesis of potassium and calcium channels' diseases, clinical features and therapeutical approach].

PubMed

Bozzola, E; Savasta, S; Peruzzi, C; Bozzola, M; Bona, G

2007-04-01

In infancy, the autosomal dominant inherited ataxias are severe neurological diseases, due to inherited mutations of ion channels. The main forms are: episodic ataxia type 1 (EA1), episodic ataxia type 2 (EA2), spinocerebellar ataxia type 6 (SCA6). EA1 is due to a mutation in KCNA1, the gene encoding human Kv1.1 on chromosome 12p13, which contributes as a subunit to the formation of potassium channels in motor nerve terminals and in many central nervous system neurones. To date, there are fifteen different mutations, which affect potassium channel's properties and lead to phenotypic variability and to different responses to therapy. EA2 can result from mutations in the CACNA1A gene, encoding calcium channels on chromosome 19p13.1 and widely distributed throughout the central nervous system. To date, associated with EA2, in the CACNA1A gene thirty different mutations have been described, resulting in altered or truncated protein products and, as a consequence, in nonfunctional calcium channels. There is phenotypic variability, also inside the same family, without correlation genotype-phenotype. SCA6 is a progressive neurodegenerative disease due to mutations of the CACNA1A gene. CACNA1A is responsible for both EA2 and SCA6. Nevertheless, the pathogenesis of the two diseases is different: SCA6 is associated with small expansion of a CAGn repeat, while EA2 is due to point mutations. Clinically, SCA6 is characterized by a slowly progressive development and by an inverse correlation between the number of repeats and the severity of the disease.

Hyperpolarization-Activated Current Induces Period-Doubling Cascades and Chaos in a Cold Thermoreceptor Model

PubMed Central

Xu, Kesheng; Maidana, Jean P.; Caviedes, Mauricio; Quero, Daniel; Aguirre, Pablo; Orio, Patricio

2017-01-01

In this article, we describe and analyze the chaotic behavior of a conductance-based neuronal bursting model. This is a model with a reduced number of variables, yet it retains biophysical plausibility. Inspired by the activity of cold thermoreceptors, the model contains a persistent Sodium current, a Calcium-activated Potassium current and a hyperpolarization-activated current (Ih) that drive a slow subthreshold oscillation. Driven by this oscillation, a fast subsystem (fast Sodium and Potassium currents) fires action potentials in a periodic fashion. Depending on the parameters, this model can generate a variety of firing patterns that includes bursting, regular tonic and polymodal firing. Here we show that the transitions between different firing patterns are often accompanied by a range of chaotic firing, as suggested by an irregular, non-periodic firing pattern. To confirm this, we measure the maximum Lyapunov exponent of the voltage trajectories, and the Lyapunov exponent and Lempel-Ziv's complexity of the ISI time series. The four-variable slow system (without spiking) also generates chaotic behavior, and bifurcation analysis shows that this is often originated by period doubling cascades. Either with or without spikes, chaos is no longer generated when the Ih is removed from the system. As the model is biologically plausible with biophysically meaningful parameters, we propose it as a useful tool to understand chaotic dynamics in neurons. PMID:28344550

Sodium and potassium intakes among US adults: NHANES 2003–20081234

PubMed Central

Zhang, Zefeng; Carriquiry, Alicia L; Gunn, Janelle P; Kuklina, Elena V; Saydah, Sharon H; Yang, Quanhe; Moshfegh, Alanna J

2012-01-01

Background: The American Heart Association (AHA), Institute of Medicine (IOM), and US Departments of Health and Human Services and Agriculture (USDA) Dietary Guidelines for Americans all recommend that Americans limit sodium intake and choose foods that contain potassium to decrease the risk of hypertension and other adverse health outcomes. Objective: We estimated the distributions of usual daily sodium and potassium intakes by sociodemographic and health characteristics relative to current recommendations. Design: We used 24-h dietary recalls and other data from 12,581 adults aged ≥20 y who participated in NHANES in 2003–2008. Estimates of sodium and potassium intakes were adjusted for within-individual day-to-day variation by using measurement error models. SEs and 95% CIs were assessed by using jackknife replicate weights. Results: Overall, 99.4% (95% CI: 99.3%, 99.5%) of US adults consumed more sodium daily than recommended by the AHA (<1500 mg), and 90.7% (89.6%, 91.8%) consumed more than the IOM Tolerable Upper Intake Level (2300 mg). In US adults who are recommended by the Dietary Guidelines to further reduce sodium intake to 1500 mg/d (ie, African Americans aged ≥51 y or persons with hypertension, diabetes, or chronic kidney disease), 98.8% (98.4%, 99.2%) overall consumed >1500 mg/d, and 60.4% consumed >3000 mg/d—more than double the recommendation. Overall, <2% of US adults and ∼5% of US men consumed ≥4700 mg K/d (ie, met recommendations for potassium). Conclusion: Regardless of recommendations or sociodemographic or health characteristics, the vast majority of US adults consume too much sodium and too little potassium. PMID:22854410

The wheat NHX antiporter gene TaNHX2 confers salt tolerance in transgenic alfalfa by increasing the retention capacity of intracellular potassium.

PubMed

Zhang, Yan-Min; Zhang, Hong-Mei; Liu, Zi-Hui; Li, Hui-Cong; Guo, Xiu-Lin; Li, Guo-Liang

2015-02-01

Previous studies have shown that TaNHX2 transgenic alfalfa (Medicago sativa L.) accumulated more K(+) and less Na(+) in leaves than did the wild-type plants. To investigate whether the increased K(+) accumulation in transgenic plants is attributed to TaNHX2 gene expression and whether the compartmentalization of Na(+) into vacuoles or the intracellular compartmentalization of potassium is the critical mechanism for TaNHX2-dependent salt tolerance in transgenic alfalfa, aerated hydroponic culture was performed under three different stress conditions: control condition (0.1 mM Na(+) and 6 mM K(+) inside culture solution), K(+)-sufficient salt stress (100 mM NaCl and 6 mM K(+)) and K(+)-insufficient salt stress (100 mM NaCl and 0.1 mM K(+)). The transgenic alfalfa plants had lower K(+) efflux through specific K(+) channels and higher K(+) absorption through high-affinity K(+) transporters than did the wild-type plants. Therefore, the transgenic plants had greater K(+) contents and [K(+)]/[Na(+)] ratios in leaf tissue and cell sap. The intracellular compartmentalization of potassium is critical for TaNHX2-induced salt tolerance in transgenic alfalfa.

Calcium-dependent inactivation of calcium channels in cochlear hair cells of the chicken.

PubMed

Lee, Seunghwan; Briklin, Olga; Hiel, Hakim; Fuchs, Paul

2007-09-15

Voltage-gated calcium channels support both spontaneous and sound-evoked neurotransmitter release from ribbon synapses of cochlear hair cells. A variety of regulatory mechanisms must cooperate to ensure the appropriate level of activity in the restricted pool of synaptic calcium channels ( approximately 100) available to each synaptic ribbon. One potential feedback mechanism, calcium-dependent inactivation (CDI) of voltage-gated, L-type calcium channels, can be modulated by calmodulin-like calcium-binding proteins. CDI of voltage-gated calcium current was studied in hair cells of the chicken's basilar papilla (analogous to the mammalian cochlea) after blocking the predominant potassium conductances. For inactivating currents produced by 2.5 s steps to the peak of the current-voltage relation (1 mm EGTA internal calcium buffer), single exponential fits yielded an average decay time constant of 1.92 +/- 0.18 s (mean +/- s.e.m., n = 12) at 20-22 degrees C, while recovery occurred with a half-time of approximately 10 s. Inactivation produced no change in reversal potential, arguing that the observed relaxation did not result from alternative processes such as calcium accumulation or activation of residual potassium currents. Substitution of external calcium with barium greatly reduced inactivation, while inhibition of endoplasmic calcium pumps with t-benzohydroquinone (BHQ) or thapsigargin made inactivation occur faster and to a greater extent. Raising external calcium 10-fold (from 2 to 20 mm) increased peak current 3-fold, but did not alter the extent or time course of CDI. However, increasing levels of internal calcium buffer consistently reduced the rate and extent of inactivation. With 1 mm EGTA buffering and in 2 mm external calcium, the available pool of calcium channels was half-inactivated near the resting membrane potential (-50 mV). CDI may be further regulated by calmodulin-like calcium-binding proteins (CaBPs). mRNAs for several CaBPs are expressed in chicken cochlear tissue, and antibodies to CaBP4 label hair cells, but not supporting cells, equivalent to the pattern seen in mammalian cochlea. Thus, molecular mechanisms that underlie CDI appeared to be conserved across vertebrate species, may provide a means to adjust calcium channel open probability, and could serve to maintain the set-point for spontaneous release from the ribbon synapse.

Time to Consider Use of the Sodium-to-Potassium Ratio for Practical Sodium Reduction and Potassium Increase

PubMed Central

Miura, Katsuyuki; Ueshima, Hirotsugu

2017-01-01

Pathogenetic studies have demonstrated that the interdependency of sodium and potassium affects blood pressure. Emerging evidences on the sodium-to-potassium ratio show benefits for a reduction in sodium and an increase in potassium compared to sodium and potassium separately. As presently there is no known review, this article examined the practical use of the sodium-to-potassium ratio in daily practice. Epidemiological studies suggest that the urinary sodium-to-potassium ratio may be a superior metric as compared to separate sodium and potassium values for determining the relation to blood pressure and cardiovascular disease risks. Higher correlations and better agreements are seen for the casual urine sodium-to-potassium ratio than for casual urine sodium or potassium alone when compared with the 24-h urine values. Repeated measurements of the casual urine provide reliable estimates of the 7-day 24-h urine value with less bias for the sodium-to-potassium ratio as compared to the common formulas used for estimating the single 24-h urine from the casual urine for sodium and potassium separately. Self-monitoring devices for the urinary sodium-to-potassium ratio measurement makes it possible to provide prompt onsite feedback. Although these devices have been evaluated with a view to support an individual approach for sodium reduction and potassium increase, there has yet to be an accepted recommended guideline for the sodium-to-potassium ratio. This review concludes with a look at the practical use of the sodium-to-potassium ratio for assistance in practical sodium reduction and potassium increase. PMID:28678188

Comparison of portable crewmember protective breathing equipment (CPBE) designs.

DOT National Transportation Integrated Search

1993-04-01

CPBE presently certified for transport category aircraft employ 3 types of oxygen production systems: chlorate candle, potassium superoxide, and compressed oxygen. CPBE performance was evaluated to expose significant differences based on this distinc...

Absence of ion-binding affinity in the putatively inactivated low-[K+] structure of the KcsA potassium channel.

PubMed

Boiteux, Céline; Bernèche, Simon

2011-01-12

Potassium channels are membrane proteins that selectively conduct K(+) across cellular membranes. The narrowest part of their pore, the selectivity filter, is responsible for distinguishing K(+) from Na(+), and can also act as a gate through a mechanism known as C-type inactivation. It has been proposed that a conformation of the KcsA channel obtained by crystallization in presence of low concentration of K(+) (PDB 1K4D) could correspond to the C-type inactivated state. Here, we show using molecular mechanics simulations that such conformation has little ion-binding affinity and that ions do not contribute to its stability. The simulations suggest that, in this conformation, the selectivity filter is mostly occupied by water molecules. Whether such ion-free state of the KcsA channel is physiologically accessible and representative of the inactivated state of eukaryotic channels remains unclear. Copyright © 2011 Elsevier Ltd. All rights reserved.

Heat stress responses modulate calcium regulations and electrophysiological characteristics in atrial myocytes.

PubMed

Chen, Yao-Chang; Kao, Yu-Hsun; Huang, Chun-Feng; Cheng, Chen-Chuan; Chen, Yi-Jen; Chen, Shih-Ann

2010-04-01

Heat stress-induced responses change the ionic currents and calcium homeostasis. However, the molecular insights into the heat stress responses on calcium homeostasis remain unclear. The purposes of this study were to examine the mechanisms of heat stress responses on calcium handling and electrophysiological characteristics in atrial myocytes. We used indo-1 fluorimetric ratio technique and whole-cell patch clamp to investigate the intracellular calcium, action potentials, and ionic currents in isolated rabbit single atrial cardiomyocytes with or without (control) exposure to heat stress (43 degrees C, 15 min) 5+/-1 h before experiments. The expressions of sarcoplasmic reticulum ATPase (SERCA2a), and Na(+)-Ca(2+) exchanger (NCX) in the control and heat stress-treated atrial myocytes were evaluated by Western blot and real-time PCR. As compared with control myocytes, the heat stress-treated myocytes had larger sarcoplasmic reticulum calcium content and larger intracellular calcium transient with a shorter decay portion. Heat stress-treated myocytes also had larger L-type calcium currents, transient outward potassium currents, but smaller NCX currents. Heat stress responses increased the protein expressions, SERCA2a, NCX, and heat shock protein. However, heat stress responses did not change the RNA expression of SERCA2a and NCX. In conclusion, heat stress responses change calcium handling through protein but not RNA regulation. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Mechanism of resveratrol-induced relaxation of the guinea pig fundus.

PubMed

Tsai, Ching-Chung; Tey, Shu-Leei; Lee, Ming-Che; Liu, Ching-Wen; Su, Yu-Tsun; Huang, Shih-Che

2018-04-01

Resveratrol is a polyphenolic compound that can be isolated from plants and also is a constituent of red wine. Resveratrol induces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Impaired gastric accommodation plays an important role in functional dyspepsia and fundic relaxation and is a therapeutic target of functional dyspepsia. Although drugs for fundic relaxation have been developed, these types of drugs are still rare. The purpose of this study was to investigate the relaxant effects of resveratrol in the guinea pig fundus. We studied the relaxant effects of resveratrol in the guinea pig fundus. In addition, we investigated the mechanism of resveratrol-induced relaxation on the guinea pig fundus by using tetraethylammonium (a non-selective potassium channel blocker), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channels), glibenclamide (an ATP-sensitive potassium channel blocker), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na + channel blocker), ω-conotoxin GVIA (a selective neuronal Ca 2+ channel blocker) and G-15 (a G-protein coupled estrogen receptor antagonist). The results of this study showed that resveratrol has potent and dose-dependent relaxant effects on the guinea pig fundic muscle. In addition, the results showed that resveratrol-induced relaxation of the guinea pig fundus occurs through nitric oxide and ATP-sensitive potassium channels. This study provides the first evidence concerning the relaxant effects of resveratrol in the guinea pig fundic muscle strips. Furthermore, resveratrol may be a potential drug to relieve gastrointestinal dyspepsia. Copyright © 2018 Elsevier GmbH. All rights reserved.

Cell-autonomous excitation of midbrain dopamine neurons by endocannabinoid-dependent lipid signaling

PubMed Central

Gantz, Stephanie C.; Bean, Bruce P.

2017-01-01

SUMMARY The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood. Using a preparation of dissociated mouse midbrain dopamine neurons to isolate effects on intrinsic excitability, we found that 100 nM 2-AG accelerated pacemaking and steepened the frequency-current relationship for burst-like firing. In voltage-clamp experiments, 2-AG reduced A-type potassium current (IA) through a cannabinoid receptor-independent mechanism mimicked by arachidonic acid, which has no activity on cannabinoid receptors. Activation of orexin, neurotensin, and metabotropic glutamate Gq/11-linked receptors mimicked the effects of exogenous 2-AG and their actions were prevented by inhibiting the 2-AG-synthesizing enzyme diacylglycerol lipase α. The results show that 2-AG and related lipid signaling molecules can directly tune neuronal excitability in a cell-autonomous manner by modulating IA. PMID:28262417

Physiology and pathophysiology of potassium homeostasis.

PubMed

Palmer, Biff F; Clegg, Deborah J

2016-12-01

Total body potassium content and proper distribution of potassium across the cell membrane is of critical importance for normal cellular function. Potassium homeostasis is maintained by several different methods. In the kidney, total body potassium content is achieved by alterations in renal excretion of potassium in response to variations in intake. Insulin and beta-adrenergic tone play critical roles in maintaining the internal distribution of potassium under normal conditions. Despite homeostatic pathways designed to maintain potassium levels within the normal range, disorders of altered potassium homeostasis are common. The clinical approach to designing effective treatments relies on understanding the pathophysiology and regulatory influences which govern the internal distribution and external balance of potassium. Here we provide an overview of the key regulatory aspects of normal potassium physiology. This review is designed to provide an overview of potassium homeostasis as well as provide references of seminal papers to guide the reader into a more in depth discussion of the importance of potassium balance. This review is designed to be a resource for educators and well-informed clinicians who are teaching trainees about the importance of potassium balance. Copyright © 2016 the American Physiological Society.

Tables Of Gaussian-Type Orbital Basis Functions

NASA Technical Reports Server (NTRS)

Partridge, Harry

1992-01-01

NASA technical memorandum contains tables of estimated Hartree-Fock wave functions for atoms lithium through neon and potassium through krypton. Sets contain optimized Gaussian-type orbital exponents and coefficients, and near Hartree-Fock quality. Orbital exponents optimized by minimizing restricted Hartree-Fock energy via scaled Newton-Raphson scheme in which Hessian evaluated numerically by use of analytically determined gradients.

Single cell analysis of voltage-gated potassium channels that determines neuronal types of rat hypothalamic paraventricular nucleus neurons.

PubMed

Lee, S K; Lee, S; Shin, S Y; Ryu, P D; Lee, S Y

2012-03-15

The hypothalamic paraventricular nucleus (PVN), a site for the integration of both the neuroendocrine and autonomic systems, has heterogeneous cell composition. These neurons are classified into type I and type II neurons based on their electrophysiological properties. In the present study, we investigated the molecular identification of voltage-gated K+ (Kv) channels, which determines a distinctive characteristic of type I PVN neurons, by means of single-cell reverse transcription-polymerase chain reaction (RT-PCR) along with slice patch clamp recordings. In order to determine the mRNA expression profiles, firstly, the PVN neurons of male rats were classified into type I and type II neurons, and then, single-cell RT-PCR and single-cell real-time RT-PCR analysis were performed using the identical cell. The single-cell RT-PCR analysis revealed that Kv1.2, Kv1.3, Kv1.4, Kv4.1, Kv4.2, and Kv4.3 were expressed both in type I and in type II neurons, and several Kv channels were co-expressed in a single PVN neuron. However, we found that the expression densities of Kv4.2 and Kv4.3 were significantly higher in type I neurons than in type II neurons. Taken together, several Kv channels encoding A-type K+ currents are present both in type I and in type II neurons, and among those, Kv4.2 and Kv4.3 are the major Kv subunits responsible for determining the distinct electrophysiological properties. Thus these 2 Kv subunits may play important roles in determining PVN cell types and regulating PVN neuronal excitability. This study further provides key molecular mechanisms for differentiating type I and type II PVN neurons. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Regulation of the instantaneous inward rectifier and the delayed outward rectifier potassium channels by Captopril and Angiotensin II via the Phosphoinositide-3 kinase pathway in volume-overload-induced hypertrophied cardiac myocytes.

PubMed

Alvin, Zikiar V; Laurence, Graham G; Coleman, Bernell R; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E

2011-07-01

Early development of cardiac hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents can be modulated by the activation of humoral factors, such as angiotensin II (ANG II) through protein kinases. The aim of this work is to assess the regulation of IK and IK1 by ANG II through the PI3-K pathway in hypertrophied ventricular myocytes. Cardiac eccentric hypertrophy was induced through volume-overload in adult male rats by aorto-caval shunt (3 weeks). After one week half of the rats were given captopril (2 weeks; 0.5 g/l/day) and the other half served as control. The voltage-clamp and western blot techniques were used to measure the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity, respectively. Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10-6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts, but not in sham. Captopril treatment reversed ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin converting enzyme inhibition, ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Thus, captopril treatment reveals a negative effect of ANG II on IK and IK1, which is PI3-K independent, whereas in the absence of angiotensin converting enzyme inhibition IK and IK1 regulation is dependent upon PI3-K.

The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression.

PubMed

Teah, Yi Fan; Abduraman, Muhammad Asyraf; Amanah, Azimah; Adenan, Mohd Ilham; Sulaiman, Shaida Fariza; Tan, Mei Lan

2017-09-01

Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. Human ether-a-go-go-related gene (hERG) encodes the cardiac I Kr current which is a determinant of the duration of ventricular action potentials and QT interval. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 μM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 μM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and I kr blocker. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electrical Engineering (Selected Articles).

DTIC Science & Technology

1980-05-15

Homopolar Machine with Sodium-Potassium Ring-Shaped Contacts, by L.A. Sukhanov , G.A. Karmonov .......... 19 ACCESSION forWht hieSeto NTISuf ecine 1DOCS...3663 FACE 19 DIFECT-CURRENT HOMOPOLAS AACHIhI ITH SCIIUM-ECIASSIUM RING-SHAPED CONTACTS L. A. Sukhanov , Cand. tech. sciences, G. A. Karmanov, eng. ThA

Nicotine inhibits potassium currents in Aplysia bag cell neurons

PubMed Central

White, Sean H.; Sturgeon, Raymond M.

2016-01-01

Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPβS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K+ with Cs+. Consistent with an underlying mechanism of direct inhibition of one or more K+ channels, nicotine was found to rapidly reduce the fast-inactivating A-type K+ current as well as both components of the delayed-rectifier K+ current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K+ channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time. PMID:26864763

A role of stretch-activated potassium currents in the regulation of uterine smooth muscle contraction

PubMed Central

Buxton, Iain L O; Heyman, Nathanael; Wu, Yi-ying; Barnett, Scott; Ulrich, Craig

2011-01-01

Rates of premature birth are alarming and threaten societies and healthcare systems worldwide. Premature labor results in premature birth in over 50% of cases. Preterm birth accounts for three-quarters of infant morbidity and mortality. Children that survive birth before 34 weeks gestation often face life-long disability. Current treatments for preterm labor are wanting. No treatment has been found to be generally effective and none are systematically evaluated beyond 48 h. New approaches to the treatment of preterm labor are desperately needed. Recent studies from our laboratory suggest that the uterine muscle is a unique compartment with regulation of uterine relaxation unlike that of other smooth muscles. Here we discuss recent evidence that the mechanically activated 2-pore potassium channel, TREK-1, may contribute to contraction-relaxation signaling in uterine smooth muscle and that TREK-1 gene variants associated with human labor and preterm labor may lead to a better understanding of preterm labor and its possible prevention. PMID:21642947

Current Pharmacological Management of Gastroesophageal Reflux Disease

PubMed Central

Wang, Yao-Kuang; Hsu, Wen-Hung; Wang, Sophie S. W.; Lu, Chien-Yu; Kuo, Fu-Chen; Su, Yu-Chung; Yang, Sheau-Fang; Chen, Chiao-Yun; Wu, Deng-Chyang

2013-01-01

Gastroesophageal reflux disease (GERD), a common disorder with troublesome symptoms caused by reflux of gastric contents into the esophagus, has adverse impact on quality of life. A variety of medications have been used in GERD treatment, and acid suppression therapy is the mainstay of treatment for GERD. Although proton pump inhibitor is the most potent acid suppressant and provides good efficacy in esophagitis healing and symptom relief, about one-third of patients with GERD still have persistent symptoms with poor response to standard dose PPI. Antacids, alginate, histamine type-2 receptor antagonists, and prokinetic agents are usually used as add-on therapy to PPI in clinical practice. Development of novel therapeutic agents has focused on the underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxation, motility disorder, mucosal protection, and esophageal hypersensitivity. Newer formulations of PPI with faster and longer duration of action and potassium-competitive acid blocker, a newer acid suppressant, have also been investigated in clinical trials. In this review, we summarize the current and developing therapeutic agents for GERD treatment. PMID:23878534

Energy generation by fermentation of glucose in a batch flow microbial fuel cell

NASA Astrophysics Data System (ADS)

Badea, Silviu-Laurentiu; Enache, Stanica; Tamaian, Radu; Buga, Mihaela-Ramona; Pirvu, Cristian; Varlam, Mihai

2016-04-01

In the last years, microbial fuel cells (MFCs) have emerged like a novel research technologies for production of sustainable and clean electricity energy through bioxidation of organic materials, representing a promising alternative to combustion energy sources. In this study, production of bioelectricity in MFC in batch system (dual chambered MFC) was investigated. A dual chambered MFC from glass was built for this purpose. Saccharomyces cerevisiae as an active biocatalyst was explored for power generation. Graphite plates were used as electrodes and glucose as substrate. Saccharomyces cerevisiae was initially grown on a period of 72h at 30 degree Celsius, on medium of modified Sabouraud liquid medium containing 30 g glucose/L. A volume of inoculated medium (80 mL) was transferred in the anode compartment of MFC together with 20 mL glucose 1M, while neutral red was used as mediator (electron shuttle) in concentration of 200 μM in anaerobic anode chamber. Potassium permanganate (KMnO4) was used as oxidizing agent in the cathode in wide concentration range (400 μM-40 000 μM). Cathodic compartment was loaded initially with 40 mM potassium permanganate, and afterwards was supplied two times more with KMnO4 of the same concentration, in order to maintain MFC functionality. The MFC was operated on a water bath heated by a combined hot-plate magnetic-stirrer device at 30 degree Celsius and mixed at 180 rpm. The maximum open circuit potential (OCV) recorded of about 0.6 V was reached after the 3rd loading with 40 milimolles of potassium permanganate. Using a potentiostat, the polarization curve was recorded by varying the potential between 0.5 V and 0.0 V, while the intensity of current increased from 0.0 to about 1.5 mA respectively, corresponding to an anodic current density of about 0.81 A/m2. In order to optimize the design and performance of the MFC, the goal of the further research is to use variously concentrations of potassium permanganate. Furthermore, a dual chambered MFC of large volume (0.5 L), a nafion membrane between anodic and cathodic compartments, and recirculation flows of glucose and potassium permanganate are planned to be used for a longer operability of the MFC.

Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation

PubMed Central

Tsai, Chia-Ti; Hsieh, Chia-Shan; Chang, Sheng-Nan; Chuang, Eric Y.; Ueng, Kwo-Chang; Tsai, Chin-Feng; Lin, Tsung-Hsien; Wu, Cho-Kai; Lee, Jen-Kuang; Lin, Lian-Yu; Wang, Yi-Chih; Yu, Chih-Chieh; Lai, Ling-Ping; Tseng, Chuen-Den; Hwang, Juey-Jen; Chiang, Fu-Tien; Lin, Jiunn-Lee

2016-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 × 10−24). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor of AF risk possibly pointing to a functional pathway. PMID:26831368

Diagnostic value of potassium level in a spot urine sample as an index of 24-hour urinary potassium excretion in unselected patients hospitalized in a hypertension unit

PubMed Central

Symonides, Bartosz; Wojciechowska, Ewa; Gryglas, Adam; Gaciong, Zbigniew

2017-01-01

Background Primary hyperaldosteronism may be associated with elevated 24-hour urinary potassium excretion. We evaluated the diagnostic value of spot urine (SU) potassium as an index of 24-hour urinary potassium excretion. Methods We measured SU and 24-hour urinary collection potassium and creatinine in 382 patients. Correlations between SU and 24-hour collections were assessed for potassium levels and potassium/creatinine ratios. We used the PAHO formula to estimate 24-hour urinary potassium excretion based on SU potassium level. The agreement between estimated and measured 24-hour urinary potassium excretion was evaluated using the Bland-Altman method. To evaluate diagnostic performance of SU potassium, we calculated areas under the curve (AUC) for SU potassium/creatinine ratio and 24-hour urinary potassium excretion estimated using the PAHO formula. Results Strongest correlation between SU and 24-hour collection was found for potassium/creatinine ratio (r = 0.69, P<0.001). The PAHO formula underestimated 24-hour urinary potassium excretion by mean 8.3±18 mmol/d (95% limits of agreement -28 to +44 mmol/d). Diagnostic performance of SU potassium/creatinine ratio was borderline good only if 24-hour urinary potassium excretion was largely elevated (AUC 0.802 for 120 mmol K+/24 h) but poor with lower values (AUC 0.696 for 100 mmol K+/24 h, 0.636 for 80 mmol K+/24 h, 0.675 for 40 mmol K+/24 h). Diagnostic performance of 24-hour urinary potassium excretion estimated by the PAHO formula was excellent with values above 120 mmol/d and good with lower values (AUC 0.941 for 120 mmol K+/24 h, 0.819 for 100 mmol K+/24 h, 0.823 for 80 mmol K+/24 h, 0.836 for 40 mmol K+/24 h). Conclusions Spot urine potassium/creatinine ratio might be a marker of increased 24-hour urinary potassium excretion and a potentially useful screening test when reliable 24-hour urine collection is not available. The PAHO formula allowed estimation of the 24-hour urinary potassium excretion based on SU measurements with reasonable clinical accuracy. PMID:28662194

Experimental patch testing with chromium-coated materials.

PubMed

Bregnbak, David; Thyssen, Jacob P; Jellesen, Morten S; Zachariae, Claus; Johansen, Jeanne D

2017-06-01

Chromium coatings on metal alloys can be decorative, and prevent corrosion and metal ion release. We recently showed that handling of a chromium-containing disc resulted in chromium deposition on the skin. To examine patch test reactivity to chromium-coated discs. We included 15 patients: 10 chromium-allergic patients, and 5 patients without chromium allergy. All were patch tested with potassium dichromate, cobalt chloride, nickel sulfate, and nine different metallic discs. The chromium-allergic patients were also patch tested with serial dilutions of potassium dichromate. Positive/weaker reactions were observed to disc B (1 of 10), disc C (1 of 10), and disc D, disc E, and disc I (4 of 10 each). As no controls reacted to any of the discs, the weak reactions indicate allergic reactions. Positive patch test reactions to 1770 ppm chromium(VI) in the serial dilutions of potassium dichromate were observed in 7 of 10 patients. When the case group was narrowed down to include only the patients with a current positive patch test reaction to potassium dichromate, elicitation of dermatitis by both chromium(III) and chromium(VI) discs was observed in 4 of 7 of patients. Many of the patients reacted to both chromium(III) and chromium(VI) surfaces. Our results indicate that both chromium(VI) and chromium(III) pose a risk to chromium-allergic patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Insulin increases excitability via a dose-dependent dual inhibition of voltage-activated K+ currents in differentiated N1E-115 neuroblastoma cells.

PubMed

Lima, Pedro A; Vicente, M Inês; Alves, Frederico M; Dionísio, José C; Costa, Pedro F

2008-04-01

A role in the control of excitability has been attributed to insulin via modulation of potassium (K(+)) currents. To investigate insulin modulatory effects on voltage-activated potassium currents in a neuronal cell line with origin in the sympathetic system, we performed whole-cell voltage-clamp recordings in differentiated N1E-115 neuroblastoma cells. Two main voltage-activated K(+) currents were identified: (a) a relatively fast inactivating current (I(fast) - time constant 50-300 ms); (b) a slow delayed rectifying K(+) current (I(slow) - time constant 1-4 s). The kinetics of inactivation of I(fast), rather than I(slow), showed clear voltage dependence. I(fast) and I(slow) exhibited different activation and inactivation dependence for voltage, and have different but nevertheless high sensitivities to tetraethylammonium, 4-aminopyridine and quinidine. In differentiated cells - rather than in non-differentiated cells - application of up to 300 nm insulin reduced I(slow) only (IC(50) = 6.7 nm), whereas at higher concentrations I(fast) was also affected (IC(50) = 7.7 microm). The insulin inhibitory effect is not due to a change in the activation or inactivation current-voltage profiles, and the time-dependent inactivation is also not altered; this is not likely to be a result of activation of the insulin-growth-factor-1 (IGF1) receptors, as application of IGF1 did not result in significant current alteration. Results suggest that the current sensitive to low concentrations of insulin is mediated by erg-like channels. Similar observations concerning the insulin inhibitory effect on slow voltage-activated K(+) currents were also made in isolated rat hippocampal pyramidal neurons, suggesting a widespread neuromodulator role of insulin on K(+) channels.

21 CFR 184.1613 - Potassium bicarbonate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium bicarbonate. 184.1613 Section 184.1613... Listing of Specific Substances Affirmed as GRAS § 184.1613 Potassium bicarbonate. (a) Potassium... potassium hydroxide with carbon dioxide; (2) By treating a solution of potassium carbonate with carbon...

21 CFR 184.1613 - Potassium bicarbonate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium bicarbonate. 184.1613 Section 184.1613... Listing of Specific Substances Affirmed as GRAS § 184.1613 Potassium bicarbonate. (a) Potassium... potassium hydroxide with carbon dioxide; (2) By treating a solution of potassium carbonate with carbon...

21 CFR 184.1613 - Potassium bicarbonate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium bicarbonate. 184.1613 Section 184.1613... Listing of Specific Substances Affirmed as GRAS § 184.1613 Potassium bicarbonate. (a) Potassium... potassium hydroxide with carbon dioxide; (2) By treating a solution of potassium carbonate with carbon...

21 CFR 184.1613 - Potassium bicarbonate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium bicarbonate. 184.1613 Section 184.1613... Listing of Specific Substances Affirmed as GRAS § 184.1613 Potassium bicarbonate. (a) Potassium... potassium hydroxide with carbon dioxide; (2) By treating a solution of potassium carbonate with carbon...

Direct block of hERG potassium channels by the protein kinase C inhibitor bisindolylmaleimide I (GF109203X).

PubMed

Thomas, Dierk; Hammerling, Bettina C; Wimmer, Anna-Britt; Wu, Kezhong; Ficker, Eckhard; Kuryshev, Yuri A; Scherer, Daniel; Kiehn, Johann; Katus, Hugo A; Schoels, Wolfgang; Karle, Christoph A

2004-12-01

The human ether-a-go-go-related gene (hERG) encodes the rapid component of the cardiac repolarizing delayed rectifier potassium current, I(Kr). The direct interaction of the commonly used protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIM I) with hERG, KvLQT1/minK, and I(Kr) currents was investigated in this study. hERG and KvLQT1/minK channels were heterologously expressed in Xenopus laevis oocytes, and currents were measured using the two-microelectrode voltage clamp technique. In addition, hERG currents in stably transfected human embryonic kidney (HEK 293) cells, native I(Kr) currents and action potentials in isolated guinea pig ventricular cardiomyocytes were recorded using whole-cell patch clamp electrophysiology. Bisindolylmaleimide I blocked hERG currents in HEK 293 cells and Xenopus oocytes in a concentration-dependent manner with IC(50) values of 1.0 and 13.2 muM, respectively. hERG channels were primarily blocked in the open state in a frequency-independent manner. Analysis of the voltage-dependence of block revealed a reduction of inhibition at positive membrane potentials. BIM I caused a shift of -20.3 mV in the voltage-dependence of inactivation. The point mutations tyrosine 652 alanine (Y652A) and phenylalanine 656 alanine (F656A) attenuated hERG current blockade, indicating that BIM I binds to a common drug receptor within the pore region. KvLQT1/minK currents were not significantly altered by BIM I. Finally, 1 muM BIM I reduced native I(Kr) currents by 69.2% and lead to action potential prolongation. In summary, PKC-independent effects have to be carefully considered when using BIM I as PKC inhibitor in experimental models involving hERG channels and I(Kr) currents.

Effects of n-alkanols and a methyl ester on a transient potassium (IA) current in identified neurones from Helix aspersa.

PubMed Central

Winpenny, J P; Elliott, J R; Harper, A A

1992-01-01

1. A two-microelectrode voltage clamp was used to determine the effects of n-butanol, n-hexanol, n-octanol, n-decanol and methyl hexanoate on a transient potassium (IA) current in identified Helix aspersa neurones. Experiments were carried out at a temperature of 10-12 degrees C. 2. Each n-alkanol reversibly reduced the amplitude of the IA current. Logarithmic dose-response curves for the current reduction by each homologue were sigmoidal and had slope factors of around four. The concentrations required to reduce the peak (with time) current at -30 mV by 50% (ED50 +/- fitted standard error) were: 57 +/- 5 mM (n-butanol); 2.0 +/- 0.1 mM (n-hexanol); 0.28 +/- 0.02 mM (n-octanol) and 0.016 +/- 0.001 mM (n-decanol). Methyl hexanoate also reduced the current amplitude, with an ED50 of 1-2 mM. The Helix IA current thus showed a similar sensitivity to n-alkanols to that of squid and rat sodium currents but was rather more sensitive than the squid delayed rectifier potassium current. 3. The n-alkanol ED50 concentrations were used to calculate a standard free energy per methylene group for adsorption to a site of action in the cell of -3.1 +/- 0.2 kJ/mol. This suggested a hydrophobic site or sites of action. The regularity of the change in free energy with chain length was maintained up to, and including, n-decanol. This implied that the site(s) could accommodate a ten-carbon chain as readily as an eight-carbon chain. 4. The voltage dependencies of IA current activation and steady-state inactivation were not consistently altered by treatment with n-alkanols at concentrations around or above their current suppression ED50 concentrations. 5. The kinetics of current activation and inactivation were affected, particularly by lower chain length compounds. At 60 mM n-butanol reduced the time constant for development of inactivation of open channels (tau b) by 56%, while 0.016 mM n-decanol produced only a 13% reduction. n-Butanol (60 mM) also caused a substantial (76%) reduction in the time constant for development of inactivation in channels which were presumed to be closed. The effects of n-alkanols on the current time-to-peak (tc) were complex, showing both increases and decreases, but these actions also declined with chain length. Methyl hexanoate (1 mM) reduced tau b by around 30% and tc by around 20%. 6. n-Alkanols have now been shown to inhibit a number of voltage-gated ion conductances.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1293276

Interaction between synaptic inhibition and glial-potassium dynamics leads to diverse seizure transition modes in biophysical models of human focal seizures.

PubMed

Y Ho, E C; Truccolo, Wilson

2016-10-01

How focal seizures initiate and evolve in human neocortex remains a fundamental problem in neuroscience. Here, we use biophysical neuronal network models of neocortical patches to study how the interaction between inhibition and extracellular potassium ([K (+)] o ) dynamics may contribute to different types of focal seizures. Three main types of propagated focal seizures observed in recent intracortical microelectrode recordings in humans were modelled: seizures characterized by sustained (∼30-60 Hz) gamma local field potential (LFP) oscillations; seizures where the onset in the propagated site consisted of LFP spikes that later evolved into rhythmic (∼2-3 Hz) spike-wave complexes (SWCs); and seizures where a brief stage of low-amplitude fast-oscillation (∼10-20 Hz) LFPs preceded the SWC activity. Our findings are fourfold: (1) The interaction between elevated [K (+)] o (due to abnormal potassium buffering by glial cells) and the strength of synaptic inhibition plays a predominant role in shaping these three types of seizures. (2) Strengthening of inhibition leads to the onset of sustained narrowband gamma seizures. (3) Transition into SWC seizures is obtained either by the weakening of inhibitory synapses, or by a transient strengthening followed by an inhibitory breakdown (e.g. GABA depletion). This reduction or breakdown of inhibition among fast-spiking (FS) inhibitory interneurons increases their spiking activity and leads them eventually into depolarization block. Ictal spike-wave discharges in the model are then sustained solely by pyramidal neurons. (4) FS cell dynamics are also critical for seizures where the evolution into SWC activity is preceded by low-amplitude fast oscillations. Different levels of elevated [K (+)] o were important for transitions into and maintenance of sustained gamma oscillations and SWC discharges. Overall, our modelling study predicts that the interaction between inhibitory interneurons and [K (+)] o glial buffering under abnormal conditions may explain different types of ictal transitions and dynamics during propagated seizures in human focal epilepsy.