scholarly journals Bicarbonate efflux via GABAA receptors depolarizes membrane potential and inhibits two-pore domain potassium channels of astrocytes in rat hippocampal slices

Glia ◽  
2012 ◽  
Vol 60 (11) ◽  
pp. 1761-1772 ◽  
Author(s):  
Bao-Feng Ma ◽  
Min-Jie Xie ◽  
Min Zhou
Keyword(s):  
Membrane Potential ◽  
Potassium Channels ◽  
Gabaa Receptors ◽  
Hippocampal Slices ◽  
Pore Domain

Local Anesthetic Inhibition of Baseline Potassium Channels with Two Pore Domains in Tandem 

1999 ◽  
Vol 90 (4) ◽  
pp. 1092-1102 ◽  
Author(s):  
Christoph H. Kindler ◽  
Spencer C. Yost ◽  
Andrew T. Gray
Keyword(s):  
Membrane Potential ◽  
Potassium Channels ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Resting Membrane Potential ◽  
Electrode Voltage ◽  
Primary Amino ◽  
Anesthetic Action ◽  
Pore Domain ◽  
Pore Domains

Background Recently, a new structural family of potassium channels characterized by two pore domains in tandem within their primary amino acid sequence was identified. These tandem pore domain potassium channels are not gated by voltage and appear to be involved in the control of baseline membrane conductances. The goal of this study was to identify mechanisms of local anesthetic action on these channels. Methods Oocytes of Xenopus laevis were injected with cRNA from five cloned tandem pore domain baseline potassium channels (TASK, TREK-1, TOK1, ORK1, and TWIK-1), and the effects of several local anesthetics on the heterologously expressed channels were assayed using two-electrode voltage-clamp and current-clamp techniques. Results Bupivacaine (1 mM) inhibited all studied tandem pore potassium channels, with TASK inhibited most potently. The potency of inhibition was directly correlated with the octanol: buffer distribution coefficient of the local anesthetic, with the exception of tetracaine, to which TASK is relatively insensitive. The approximate 50% inhibitory concentrations of TASK were 709 microM mepivacaine, 222 microM lidocaine, 51 microM R(+)-ropivacaine, 53 microM S(-)-ropivacaine, 668 microM tetracaine, 41 microM bupivacaine, and 39 microM etidocaine. Local anesthetics (1 mM) significantly depolarized the resting membrane potential of TASK cRNA-injected oocytes compared with saline-injected control oocytes (tetracaine 22+/-6 mV rs. 7+/-1 mV, respectively, and bupivacaine 31+/-7 mV vs. 6+/-4 mV). Conclusions Local anesthetics inhibit tandem pore domain baseline potassium channels, and they could depolarize the resting membrane potential of cells expressing these channels. Whether inhibition of these channels contributes to conduction blockade or to the adverse effects of local anesthetics remains to be determined.

scholarly journals Negative Influence by the Force: Mechanically Induced Hyperpolarization via K2P Background Potassium Channels

2021 ◽  
Vol 22 (16) ◽  
pp. 9062
Author(s):  
Miklós Lengyel ◽  
Péter Enyedi ◽  
Gábor Czirják
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Potassium Channels ◽  
Cell Types ◽  
Negative Influence ◽  
Phospholipid Bilayer ◽  
Cellular Functions ◽  
K2p Channels ◽  
K Current ◽  
Pore Domain

The two-pore domain K2P subunits form background (leak) potassium channels, which are characterized by constitutive, although not necessarily constant activity, at all membrane potential values. Among the fifteen pore-forming K2P subunits encoded by the KCNK genes, the three members of the TREK subfamily, TREK-1, TREK-2, and TRAAK are mechanosensitive ion channels. Mechanically induced opening of these channels generally results in outward K+ current under physiological conditions, with consequent hyperpolarization and inhibition of membrane potential-dependent cellular functions. In the past decade, great advances have been made in the investigation of the molecular determinants of mechanosensation, and members of the TREK subfamily have emerged among the best-understood examples of mammalian ion channels directly influenced by the tension of the phospholipid bilayer. In parallel, the crucial contribution of mechano-gated TREK channels to the regulation of membrane potential in several cell types has been reported. In this review, we summarize the general principles underlying the mechanical activation of K2P channels, and focus on the physiological roles of mechanically induced hyperpolarization.

Differential expression of two-pore domain potassium channels in rat cerebellar granule neurons

2014 ◽  
Vol 453 (4) ◽  
pp. 754-760 ◽  
Author(s):  
Paulina Burgos ◽  
Rafael Zúñiga ◽  
Pedro Domínguez ◽  
Fernando Delgado-López ◽  
Leigh D. Plant ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Differential Expression ◽  
Cerebellar Granule Neurons ◽  
Granule Neurons ◽  
Cerebellar Granule ◽  
Pore Domain

scholarly journals Expression of TASK and TREK, two-pore domain K+ channels, in human myometrium

Reproduction ◽  
2005 ◽  
Vol 129 (4) ◽  
pp. 525-530 ◽  
Author(s):  
Xilian Bai ◽  
George J Bugg ◽  
Susan L Greenwood ◽  
Jocelyn D Glazier ◽  
Colin P Sibley ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Pregnant Women ◽  
Human Myometrium ◽  
Rt Pcr ◽  
Excitable Cells ◽  
K Channels ◽  
Myometrial Cells ◽  
Channel Proteins ◽  
A Site ◽  
Pore Domain

Two-pore domain K+channels are an emerging family of K+channels that may contribute to setting membrane potential in both electrically excitable and non-excitable cells and, as such, influence cellular function. The human uteroplacental unit contains both excitable (e.g. myometrial) and non-excitable cells, whose function depends upon the activity of K+channels. We have therefore investigated the expression of two members of this family, TWIK (two-pore domain weak inward rectifying K+channel)-related acid-sensitive K+channel (TASK) and TWIK-related K+channel (TREK) in human myometrium. Using RT-PCR the mRNA expression of TASK and TREK isoforms was examined in myometrial tissue from pregnant women. mRNAs encoding TASK1, 4 and 5 and TREK1 were detected whereas weak or no signals were observed for TASK2, TASK3 and TREK2. Western blotting for TASK1 gave two bands of approximately 44 and 65 kDa, whereas TREK1 gave bands of approximately 59 and 90 kDa in myometrium from pregnant women. TASK1 and TREK1 immunofluorescence was prominent in intracellular and plasmalemmal locations within myometrial cells. Therefore, we conclude that the human myometrium is a site of expression for the two-pore domain K+channel proteins TASK1 and TREK1.

Intrinsic Theta-Frequency Membrane Potential Oscillations in Hippocampal CA1 Interneurons of Stratum Lacunosum-Moleculare

1999 ◽  
Vol 81 (3) ◽  
pp. 1296-1307 ◽  
Author(s):  
C. Andrew Chapman ◽  
Jean-Claude Lacaille
Keyword(s):  
Membrane Potential ◽  
Hippocampal Slices ◽  
Stratum Radiatum ◽  
Potential Oscillations ◽  
Spike Threshold ◽  
Hippocampal Ca1 ◽  
Theta Frequency ◽  
Stratum Lacunosum Moleculare ◽  
Membrane Potential Oscillations

Intrinsic theta-frequency membrane potential oscillations in hippocampal CA1 interneurons of stratum lacunosum-moleculare. The ionic conductances underlying membrane potential oscillations of hippocampal CA1 interneurons located near the border between stratum lacunosum-moleculare and stratum radiatum (LM) were investigated using whole cell current-clamp recordings in rat hippocampal slices. At 22°C, when LM cells were depolarized near spike threshold by current injection, 91% of cells displayed 2–5 Hz oscillations in membrane potential, which caused rhythmic firing. At 32°C, mean oscillation frequency increased to 7.1 Hz. Oscillations were voltage dependent and were eliminated by hyperpolarizing cells 6–10 mV below spike threshold. Blockade of ionotropic glutamate and GABA synaptic transmission did not affect oscillations, indicating that they were not synaptically driven. Oscillations were eliminated by tetrodotoxin, suggesting that Na+ currents generate the depolarizing phase of oscillations. Oscillations were not affected by blocking Ca2+ currents with Cd2+ or Ca2+-free ACSF or by blocking the hyperpolarization-activated current ( I h) with Cs+. Both Ba2+ and a low concentration of 4-aminopyridine (4-AP) reduced oscillations but TEA did not. Theta-frequency oscillations were much less common in interneurons located in stratum oriens. Intrinsic membrane potential oscillations in LM cells of the CA1 region thus involve an interplay between inward Na+ currents and outward K+ currents sensitive to Ba2+ and 4-AP. These oscillations may participate in rhythmic inhibition and synchronization of pyramidal neurons during theta activity in vivo.

scholarly journals Expression of two pore‐domain potassium channels in mouse myometrial cells

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Ryan C. Smith ◽  
Kelly A. O’Connell ◽  
Giana Igwike ◽  
Andrea L. Rice ◽  
Peter W. Abel ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Myometrial Cells ◽  
Pore Domain
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