scholarly journals Interaction of local anesthetics with the K+channel pore domain

Channels ◽  
2013 ◽  
Vol 7 (3) ◽  
pp. 182-193 ◽  
Author(s):  
Noel W. Gray ◽  
Boris S. Zhorov ◽  
Edward G. Moczydlowski
Keyword(s):  
Local Anesthetics ◽  
K Channel ◽  
Channel Pore ◽  
Pore Domain

Amide Local Anesthetics Potently Inhibit the Human Tandem Pore Domain Background K+ Channel TASK-2 (KCNK5)

2003 ◽  
Vol 306 (1) ◽  
pp. 84-92 ◽  
Author(s):  
Christoph H. Kindler ◽  
Matthias Paul ◽  
Hilary Zou ◽  
Canhui Liu ◽  
Bruce D. Winegar ◽  
...  
Keyword(s):  
Local Anesthetics ◽  
K Channel ◽  
Pore Domain

Gating energetics of a voltage-dependent K+ channel pore domain

2017 ◽  
Vol 38 (16) ◽  
pp. 1472-1478 ◽  
Author(s):  
Greg Starek ◽  
J. Alfredo Freites ◽  
Simon Bernèche ◽  
Douglas J. Tobias
Keyword(s):  
K Channel ◽  
Channel Pore ◽  
Voltage Dependent ◽  
Pore Domain

scholarly journals Conformational Flexibility of the hERG K+ Channel Pore Domain

2010 ◽  
Vol 98 (3) ◽  
pp. 120a
Author(s):  
Anna Weinzinger ◽  
Kirsten Knape ◽  
Sören J. Wacker ◽  
Lars Boukharta ◽  
Bert L. de Groot
Keyword(s):  
Conformational Flexibility ◽  
K Channel ◽  
Channel Pore ◽  
Pore Domain

scholarly journals Structural Basis for pH-Gating of the K+ Channel TWIK1 at the Selectivity Filter

2021 ◽  
Author(s):  
Toby S Turney ◽  
Vivian Li ◽  
Stephen G Brohawn
Keyword(s):  
Conformational Changes ◽  
Pancreatic Beta Cells ◽  
Low Ph ◽  
Selectivity Filter ◽  
Structural Basis ◽  
K Channel ◽  
Open Conformation ◽  
Gating Mechanism ◽  
Lipid Nanodiscs ◽  
Pore Domain

TWIK1 is a widely expressed pH-gated two-pore domain K+ channel (K2P) that contributes to cardiac rhythm generation and insulin release from pancreatic beta cells. TWIK1 displays unique properties among K2Ps including low basal activity and inhibition by extracellular protons through incompletely understood mechanisms. Here, we present cryo-EM structures of TWIK1 in lipid nanodiscs at high and low pH that reveal a novel gating mechanism at the K+ selectivity filter. At high pH, TWIK1 adopts an open conformation. At low pH, protonation of an extracellular histidine results in a cascade of conformational changes that close the channel by sealing the top of the selectivity filter, displacing the helical cap to block extracellular ion access pathways, and opening gaps for lipid block of the intracellular cavity. These data provide a mechanistic understanding for extracellular pH-gating of TWIK1 and show how diverse mechanisms have evolved to gate the selectivity filter of K+ channels.

scholarly journals Modulation of the Two-pore Domain Acid-sensitive K+Channel TASK-2 (KCNK5) by Changes in Cell Volume

2001 ◽  
Vol 276 (46) ◽  
pp. 43166-43174 ◽  
Author(s):  
Marı́a Isabel Niemeyer ◽  
L. Pablo Cid ◽  
L. Felipe Barros ◽  
Francisco V. Sepúlveda
Keyword(s):  
Cell Volume ◽  
K Channel ◽  
Pore Domain

scholarly journals Cerebrovascular responses in mice deficient in the potassium channel, TREK-1

2010 ◽  
Vol 299 (2) ◽  
pp. R461-R469 ◽  
Author(s):  
Khodadad Namiranian ◽  
Eric E. Lloyd ◽  
Randy F. Crossland ◽  
Sean P. Marrelli ◽  
George E. Taffet ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Linolenic Acid ◽  
Basilar Artery ◽  
Cerebral Arteries ◽  
K Channel ◽  
Whole Cell ◽  
Middle Cerebral Arteries ◽  
Basilar Arteries ◽  
Cerebrovascular Smooth Muscle Cells ◽  
Pore Domain

We tested the hypothesis that TREK-1, a two-pore domain K channel, is involved with dilations in arteries. Because there are no selective activators or inhibitors of TREK-1, we generated a mouse line deficient in TREK-1. Endothelium-mediated dilations were not different in arteries from wild-type (WT) and TREK-1 knockout (KO) mice. This includes dilations of the middle cerebral artery to ATP, dilations of the basilar artery to ACh, and relaxations of the aorta to carbachol, a cholinergic agonist. The nitric oxide (NO) and endothelium-dependent hyperpolarizing factor components of ATP dilations were identical in the middle cerebral arteries of WT and TREK-1 KO mice. Furthermore, the NO and cyclooxygenase-dependent components were identical in the basilar arteries of the different genotypes. Dilations of the basilar artery to α-linolenic acid, an activator of TREK-1, were not affected by the absence of TREK-1. Whole cell currents recorded using patch-clamp techniques were similar in cerebrovascular smooth muscle cells (CVSMCs) from WT and TREK-1 KO mice. α-linolenic acid or arachidonic acid increased whole cell currents in CVSMCs from both WT and TREK-1 KO mice. The selective blockers of large-conductance Ca-activated K channels, penitrem A and iberiotoxin, blocked the increased currents elicited by either α-linolenic or arachidonic acid. In summary, dilations were similar in arteries from WT and TREK-1 KO mice. There was no sign of TREK-1-like currents in CVSMCs from WT mice, and there were no major differences in currents between the genotypes. We conclude that regulation of arterial diameter is not altered in mice lacking TREK-1.

Block of the background K+ channel TASK-1 contributes to arrhythmogenic effects of platelet-activating factor

2002 ◽  
Vol 282 (6) ◽  
pp. H2024-H2030 ◽  
Author(s):  
Andrea Barbuti ◽  
Satoshi Ishii ◽  
Takao Shimizu ◽  
Richard B. Robinson ◽  
Steven J. Feinmark
Keyword(s):  
Ventricular Myocytes ◽  
Platelet Activating Factor ◽  
Specific Protein ◽  
K Channel ◽  
Early Afterdepolarizations ◽  
Quiescent Cells ◽  
Selective Channel ◽  
Paf Receptor ◽  
Pore Domain ◽  
Electrophysiological Effects

Platelet-activating factor (PAF), an inflammatory phospholipid, induces ventricular arrhythmia via an unknown ionic mechanism. We can now link PAF-mediated cardiac electrophysiological effects to inhibition of a two-pore domain K+ channel [TWIK-related acid-sensitive K+background channel (TASK-1)]. Superfusion of carbamyl-PAF (C-PAF), a stable analog of PAF, over murine ventricular myocytes causes abnormal automaticity, plateau phase arrest of the action potential, and early afterdepolarizations in paced and quiescent cells from wild-type but not PAF receptor knockout mice. C-PAF-dependent currents are insensitive to Cs+ and are outwardly rectifying with biophysical properties consistent with a K+-selective channel. The current is blocked by TASK-1 inhibitors, including protons, Ba2+, Zn2+, and methanandamide, a stable analog of the endogenous lipid ligand of cannabanoid receptors. In addition, when TASK-1 is expressed in CHO cells that express an endogenous PAF receptor, superfusion of C-PAF decreases the expressed current. Like C-PAF, methanandamide evoked spontaneous activity in quiescent myocytes. C-PAF- and methanandamide-sensitive currents are blocked by a specific protein kinase C (PKC) inhibitor, implying overlapping signaling pathways. In conclusion, C-PAF blocks TASK-1 or a closely related channel, the effect is PKC dependent, and the inhibition alters the electrical activity of myocytes in ways that would be arrhythmogenic in the intact heart.

scholarly journals Residues Connecting Voltage Sensor Domain to Pore Domain in Shaker K+ Channel by Noncanonical Coupling Mechanism

2020 ◽  
Vol 118 (3) ◽  
pp. 333a
Author(s):  
Carlos Alberto Z. Bassetto Jr ◽  
Joao L. Carvalho-de-Souza ◽  
Francisco Bezanilla
Keyword(s):  
Voltage Sensor ◽  
K Channel ◽  
Coupling Mechanism ◽  
Pore Domain ◽  
Voltage Sensor Domain

scholarly journals Heterodimerization of two pore domain K+ channel TASK1 and TALK2 in living heterologous expression systems

PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0186252 ◽  
Author(s):  
Yoshiaki Suzuki ◽  
Kanako Tsutsumi ◽  
Tatsuya Miyamoto ◽  
Hisao Yamamura ◽  
Yuji Imaizumi
Keyword(s):  
Heterologous Expression ◽  
K Channel ◽  
Expression Systems ◽  
Heterologous Expression Systems ◽  
Pore Domain
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