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Extracellular K+ Concentration (extracellular + k+_concentration)
Selected AbstractsInfluence of Extracellular K+ Concentrations on Quinidine-induced K+ Current Inhibition in Rat Ventricular MyocytesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2000MICHIKO HIROTA Hypokalaemia is one of the important risk factors for development of torsades de pointes. We recently reported that hypokalaemia increased the electrocardiographic QT interval in rats treated with quinidine, but did not alter the arrhythmogenic potency of quinidine. In this study, we have investigated the influence of extracellular potassium concentration ([K+]o) on the inhibition of several types of cardiac potassium currents by quinidine. Such types of currents include the delayed rectifier potassium current (IK), the transient outward current (Ito), and the inward rectifier potassium current (IK1), as measured in isolated rat ventricular cells using patch-clamp techniques. Concentration-dependent effects of quinidine on IK, Ito, and IK1 were evaluated under both normal ([K+]o = 5.4 mM) and hypokalaemic ([K+]o = 3.5 mM) conditions. In contrast to both IK and Ito, which were barely influenced by changes in [K+]o, IK1 was significantly inhibited by hypokalaemia. Furthermore, while quinidine suppressed both IK and Ito in a concentration-dependent manner, the inhibitory potency of quinidine on these currents was not influenced by changes in [K+]o. The respective normal and hypokalaemic IC50 values for quinidine were 11.4 and 10.0 ,M (IK), and 17.6 and 17.3 ,M (Ito). Although higher concentrations of quinidine were required to inhibit IK1, the inhibitory potency of quinidine was also found to be insensitive to changes in [K+]o. Thus, in rats, the inhibitory potency of quinidine for the K+ current-types IK, Ito and IK1 is barely influenced by changes in [K+]o. These findings are consistent with our previous report showing that the QT-prolonging potency of quinidine was not altered under hypokalaemic conditions. However, whilst hypokalaemia does not affect IK or Ito, it can inhibit IK1 and can result in QT prolongation in-vivo. [source] Potassium-transporting proteins in skeletal muscle: cellular location and fibre-type differencesACTA PHYSIOLOGICA, Issue 2 2010M. Kristensen Abstract Potassium (K+) displacement in skeletal muscle may be an important factor in the development of muscle fatigue during intense exercise. It has been shown in vitro that an increase in the extracellular K+ concentration ([K+]e) to values higher than approx. 10 mm significantly reduce force development in unfatigued skeletal muscle. Several in vivo studies have shown that [K+]e increases progressively with increasing work intensity, reaching values higher than 10 mm. This increase in [K+]e is expected to be even higher in the transverse (T)-tubules than the concentration reached in the interstitium. Besides the voltage-sensitive K+ (Kv) channels that generate the action potential (AP) it is suggested that the big-conductance Ca2+ -dependent K+ (KCa1.1) channel contributes significantly to the K+ release into the T-tubules. Also the ATP-dependent K+ (KATP) channel participates, but is suggested primarily to participate in K+ release to the interstitium. Because there is restricted diffusion of K+ to the interstitium, K+ released to the T-tubules during AP propagation will be removed primarily by reuptake mediated by transport proteins located in the T-tubule membrane. The most important protein that mediates K+ reuptake in the T-tubules is the Na+,K+ -ATPase ,2 dimers, but a significant contribution of the strong inward rectifier K+ (Kir2.1) channel is also suggested. The Na+, K+, 2Cl, 1 (NKCC1) cotransporter also participates in K+ reuptake but probably mainly from the interstitium. The relative content of the different K+ -transporting proteins differs in oxidative and glycolytic muscles, and might explain the different [K+]e tolerance observed. [source] Electrical and Chemical Long-term Depression Do Not Attenuate Low-Mg2+,induced Epileptiform Activity in the Entorhinal CortexEPILEPSIA, Issue 4 2005Jörg Solger Summary:,Purpose: Low-frequency electrical and magnetic stimulation of cortical brain regions has been shown to reduce cortical excitability and to decrease the susceptibility to seizures in humans and in vivo models of epilepsy. The induction of long-term depression (LTD) or depotentiation of a seizure-related long-term potentiation has been proposed to be part of the underlying mechanism. With the low-Mg2+ -model of epilepsy, this study investigated the effect of electrical LTD, chemical LTD, and depotentiation on the susceptibility of the entorhinal cortex to epileptiform activity. Methods: The experiments were performed on isolated entorhinal cortex slices obtained from adult Wistar rats and mice. With extracellular recording techniques, we studied whether LTD induced by (a) three episodes of low-frequency paired-pulse stimulation (3 × 900 paired pulses at 1 Hz), and by (b) bath-applied N -methyl- d -aspartate (NMDA, 20 ,M) changes time-to-onset, duration, and frequency of seizure-like events (SLEs) induced by omitting MgSO4 from the artificial cerebrospinal fluid. Next we investigated the consequences of depotentiation on SLEs themselves by applying low-frequency stimulation after onset of low-Mg2+,induced epileptiform activity. Results: LTD, induced either by low-frequency stimulation or by bath-applied NMDA, had no effect on time-to-onset, duration, and frequency of SLEs compared with unconditioned slices. Low-frequency stimulation after onset of SLEs did not suppress but induced SLEs that lasted for the time of stimulation and were associated with a simultaneous increase of the extracellular K+ concentration. Conclusions: Our study demonstrates that neither conditioning LTD nor brief low-frequency stimulation decreases the susceptibility of the entorhinal cortex to low-Mg2+,induced epileptiform activity. The present study does not support the hypothesis that low-frequency brain stimulation exerts its anticonvulsant effect via the induction of LTD or depotentiation. [source] Synaptic and non-synaptic mechanisms of amygdala recruitment into temporolimbic epileptiform activitiesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2003Julia Klueva Abstract Lateral amygdala (LA) activity during synchronized-epileptiform discharges in temporolimbic circuits was investigated in rat horizontal slices containing the amygdala, hippocampus (Hip), perirhinal (Prh) and lateral entorhinal (LEnt) cortex, through multiple-site extra- and intracellular recording techniques and measurement of the extracellular K+ concentration. Application of 4-aminopyridine (50 µm) induced epileptiform discharges in all regions under study. Slow interictal-like burst discharges persisted in the Prh/LEnt/LA after disconnection of the Hip, seemed to originate in the Prh as shown from time delay analyses, and often preceded the onset of ictal-like activity. Disconnection of the amygdala resulted in de-synchronization of epileptiform discharges in the LA from those in the Prh/LEnt. Interictal-like activity was intracellularly reflected in LA projection neurons as ,-aminobutyric acid (GABA)A/B receptor-mediated synaptic responses, and depolarizing electrogenic events (spikelets) residing on the initial phase of the GABA response. Spikelets were considered antidromically conducted ectopic action potentials generated at axon terminals, as they were graded in amplitude, were not abolished through hyperpolarizing membrane responses (which effectively blocked evoked orthodromic action potentials), lacked a clear prepotential or synaptic potential, were not affected through blockers of gap junctions, and were blocked through remote application of tetrodotoxin at putative target areas of LA projection neurons. Remote application of a GABAB receptor antagonist facilitated spikelet generation. A transient elevation in the extracellular K+ level averaging 3 mm above baseline occurred in conjunction with interictal-like activity in all areas under study. We conclude that interictal-like discharges in the LA/LEnt/Prh spread in a predictable manner through the synaptic network with the Prh playing a leading role. The rise in extracellular K+ may provide a depolarizing mechanism for recruitment of interneurons and generation of ectopic action potentials at axon terminals of LA projection neurons. Antidromically conducted ectopic action potentials may provide a spreading mechanism of seizure activity mediated by diffuse axonal projections of LA neurons. [source] Potassium channel Kir4.1 macromolecular complex in retinal glial cellsGLIA, Issue 2 2006Nathan C. Connors Abstract A major role for Müller cells in the retina is to buffer changes in the extracellular K+ concentration ([K+]o) resulting from light-evoked neuronal activity. The primary K+ conductance in Müller cells is the inwardly rectifying K+ channel Kir4.1. Since this channel is constitutively active, K+ can enter or exit Müller cells depending on the state of the [K+]o. This process of [K+]o buffering by Müller cells ("K+ siphoning") is enhanced by the precise accumulation of these K+ channels at discrete subdomains of Müller cell membranes. Specifically, Kir4.1 is localized to the perivascular processes of Müller cells in animals with vascular retinas and to the endfeet of Müller cells in all species examined. The water channel aquaporin-4 (AQP4) also appears to be important for [K+]o buffering and is expressed in Müller cells in a very similar subcellular distribution pattern to that of Kir4.1. To gain a better understanding of how Müller cells selectively target K+ and water channels to discrete membrane subdomains, we addressed the question of whether Kir4.1 and AQP4 associate with the dystrophin,glycoprotein complex (DGC) in the mammalian retina. Immunoprecipitation (IP) experiments were utilized to show that Kir4.1 and AQP4 are associated with DGC proteins in rat retina. Furthermore, AQP4 was also shown to co-precipitate with Kir4.1, suggesting that both channels are tethered together by the DGC in Müller cells. This work further defines a subcellular localization mechanism in Müller cells that facilitates [K+]o buffering in the retina. © 2005 Wiley-Liss, Inc. [source] Changes in extracellular K+ concentration modulate contractility of rat and rabbit cardiac myocytes via the inward rectifier K+ current IK1THE JOURNAL OF PHYSIOLOGY, Issue 3 2004Ron Bouchard The mechanisms underlying the inotropic effect of reductions in [K+]o were studied using recordings of membrane potential, membrane current, cell shortening and [Ca2+]i in single, isolated cardiac myocytes. Three types of mammalian myocytes were chosen, based on differences in the current density and intrinsic voltage dependence of the inwardly rectifying background K+ current IK1 in each cell type. Rabbit ventricular myocytes had a relatively large IK1 with a prominent negative slope conductance whereas rabbit atrial cells expressed much smaller IK1, with little or no negative slope conductance. IK1 in rat ventricle was intermediate in both current density and slope conductance. Action potential duration is relatively short in both rabbit atrial and rat ventricular myocytes, and consequently both cell types spend much of the duty cycle at or near the resting membrane potential. Rapid increases or decreases of [K+]o elicited significantly different inotropic effects in rat and rabbit atrial and ventricular myocytes. Voltage-clamp and current-clamp experiments showed that the effects on cell shortening and [Ca2+]i following changes in [K+]o were primarily the result of the effects of alterations in IK1, which changed resting membrane potential and action potential waveform. This in turn differentially altered the balance of Ca2+ efflux via the sarcolemmal Na+,Ca2+ exchanger, Ca2+ influx via voltage-dependant Ca2+ channels and sarcoplasmic reticulum (SR) Ca2+ release in each cell type. These results support the hypothesis that the inotropic effect of alterations of [K+]o in the heart is due to significant non-linear changes in the current,voltage relation for IK1 and the resulting modulation of the resting membrane potential and action potential waveform. [source] External K+ modulates the activity of the Arabidopsis potassium channel SKOR via an unusual mechanismTHE PLANT JOURNAL, Issue 2 2006Ingela Johansson Summary Plant outward-rectifying K+ channels mediate K+ efflux from guard cells during stomatal closure and from root cells into the xylem for root,shoot allocation of potassium (K). Intriguingly, the gating of these channels depends on the extracellular K+ concentration, although the ions carrying the current are derived from inside the cell. This K+ dependence confers a sensitivity to the extracellular K+ concentration ([K+]) that ensures that the channels mediate K+ efflux only, regardless of the [K+] prevailing outside. We investigated the mechanism of K+ -dependent gating of the K+ channel SKOR of Arabidopsis by site-directed mutagenesis. Mutations affecting the intrinsic K+ dependence of gating were found to cluster in the pore and within the sixth transmembrane helix (S6), identifying an ,S6 gating domain' deep within the membrane. Mapping the SKOR sequence to the crystal structure of the voltage-dependent K+ channel KvAP from Aeropyrum pernix suggested interaction between the S6 gating domain and the base of the pore helix, a prediction supported by mutations at this site. These results offer a unique insight into the molecular basis for a physiologically important K+ -sensory process in plants. [source] Glutamate-induced post-activation inhibition of locus coeruleus neurons is mediated by AMPA/kainate receptors and sodium-dependent potassium currentsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2009Teresa Zamalloa Background and purpose:, Locus coeruleus (LC) neurons respond to sensory stimuli with a glutamate-triggered burst of spikes followed by an inhibition. The aim of our work was to characterize the inhibitory effect of glutamate in the LC. Experimental approach:, Single-unit extracellular and patch-clamp recordings were performed to examine glutamate responses in rat brain slices containing the LC. Key results:, Glutamate caused an initial activation followed by a late post-activation inhibition (PAI). Both effects were blocked by an AMPA/kainate receptor antagonist but not by NMDA or metabotropic glutamate receptor antagonists. All glutamate receptor agonists were able to activate neurons, but only AMPA and quisqualate caused inhibition. In neurons clamped at ,60 mV, glutamate and AMPA induced inward, followed by outward, currents, with the latter reversing polarity at ,110 mV. Glutamate-induced PAI was not modified by ,2 -adrenoceptor, µ opioid, A1 adenosine and GABAA/B receptor antagonists or Ca2+ -dependent release blockade, but it was reduced by raising the extracellular K+ concentration. Glutamate-induced PAI was not affected by several potassium channel, Na+/K+ pump, PKC and neuronal NO synthase inhibitors or lowering the extracellular Ca2+ concentration. The Na+ -activated K channel opener bithionol concentration-dependently potentiated glutamate-induced PAI, whereas partial (80%) Na+ replacement reduced glutamate- and AMPA-induced PAI. Finally, reverse transcription polymerase chain reaction assays showed the presence of mRNA for the Ca2+ -impermeable GluR2 subunit in the LC. Conclusions and implications:, Glutamate induces a late PAI in the LC, which may be mediated by a novel postsynaptic Na+ -dependent K+ current triggered by AMPA/kainate receptors. Mandarin translation of abstract [source] | |||||||||||||