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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(...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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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. |
format | Online Article Text |
id | pubmed-6785732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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