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Conduction through a narrow inward-rectifier K(+) channel pore

Inwardly rectifying potassium (Kir) channels play a key role in controlling membrane potentials in excitable and unexcitable cells, thereby regulating a plethora of physiological processes. G-protein–gated Kir channels control heart rate and neuronal excitability via small hyperpolarizing outward K(...

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Autores principales: Bernsteiner, Harald, Zangerl-Plessl, Eva-Maria, Chen, Xingyu, Stary-Weinzinger, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785732/
https://www.ncbi.nlm.nih.gov/pubmed/31511304
http://dx.doi.org/10.1085/jgp.201912359
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author Bernsteiner, Harald
Zangerl-Plessl, Eva-Maria
Chen, Xingyu
Stary-Weinzinger, Anna
author_facet Bernsteiner, Harald
Zangerl-Plessl, Eva-Maria
Chen, Xingyu
Stary-Weinzinger, Anna
author_sort Bernsteiner, Harald
collection PubMed
description Inwardly rectifying potassium (Kir) channels play a key role in controlling membrane potentials in excitable and unexcitable cells, thereby regulating a plethora of physiological processes. G-protein–gated Kir channels control heart rate and neuronal excitability via small hyperpolarizing outward K(+) currents near the resting membrane potential. Despite recent breakthroughs in x-ray crystallography and cryo-EM, the gating and conduction mechanisms of these channels are poorly understood. MD simulations have provided unprecedented details concerning the gating and conduction mechanisms of voltage-gated K(+) and Na(+) channels. Here, we use multi-microsecond–timescale MD simulations based on the crystal structures of GIRK2 (Kir3.2) bound to phosphatidylinositol-4,5-bisphosphate to provide detailed insights into the channel’s gating dynamics, including insights into the behavior of the G-loop gate. The simulations also elucidate the elementary steps that underlie the movement of K(+) ions through an inward-rectifier K(+) channel under an applied electric field. Our simulations suggest that K(+) permeation might occur via direct knock-on, similar to the mechanism recently shown for K(v) channels.
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spelling pubmed-67857322019-10-11 Conduction through a narrow inward-rectifier K(+) channel pore Bernsteiner, Harald Zangerl-Plessl, Eva-Maria Chen, Xingyu Stary-Weinzinger, Anna J Gen Physiol Research Articles Inwardly rectifying potassium (Kir) channels play a key role in controlling membrane potentials in excitable and unexcitable cells, thereby regulating a plethora of physiological processes. G-protein–gated Kir channels control heart rate and neuronal excitability via small hyperpolarizing outward K(+) currents near the resting membrane potential. Despite recent breakthroughs in x-ray crystallography and cryo-EM, the gating and conduction mechanisms of these channels are poorly understood. MD simulations have provided unprecedented details concerning the gating and conduction mechanisms of voltage-gated K(+) and Na(+) channels. Here, we use multi-microsecond–timescale MD simulations based on the crystal structures of GIRK2 (Kir3.2) bound to phosphatidylinositol-4,5-bisphosphate to provide detailed insights into the channel’s gating dynamics, including insights into the behavior of the G-loop gate. The simulations also elucidate the elementary steps that underlie the movement of K(+) ions through an inward-rectifier K(+) channel under an applied electric field. Our simulations suggest that K(+) permeation might occur via direct knock-on, similar to the mechanism recently shown for K(v) channels. Rockefeller University Press 2019-10-07 2019-09-11 /pmc/articles/PMC6785732/ /pubmed/31511304 http://dx.doi.org/10.1085/jgp.201912359 Text en © 2019 Bernsteiner et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Bernsteiner, Harald
Zangerl-Plessl, Eva-Maria
Chen, Xingyu
Stary-Weinzinger, Anna
Conduction through a narrow inward-rectifier K(+) channel pore
title Conduction through a narrow inward-rectifier K(+) channel pore
title_full Conduction through a narrow inward-rectifier K(+) channel pore
title_fullStr Conduction through a narrow inward-rectifier K(+) channel pore
title_full_unstemmed Conduction through a narrow inward-rectifier K(+) channel pore
title_short Conduction through a narrow inward-rectifier K(+) channel pore
title_sort conduction through a narrow inward-rectifier k(+) channel pore
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785732/
https://www.ncbi.nlm.nih.gov/pubmed/31511304
http://dx.doi.org/10.1085/jgp.201912359
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