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Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes
Biochemical and functional studies of ion channels have shown that many of these integral membrane proteins form macromolecular signaling complexes by physically associating with many other proteins. These macromolecular signaling complexes ensure specificity and proper rates of signal transduction....
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795833/ https://www.ncbi.nlm.nih.gov/pubmed/35095560 http://dx.doi.org/10.3389/fphys.2021.796540 |
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author | Shah, Kunal R. Guan, Xin Yan, Jiusheng |
author_facet | Shah, Kunal R. Guan, Xin Yan, Jiusheng |
author_sort | Shah, Kunal R. |
collection | PubMed |
description | Biochemical and functional studies of ion channels have shown that many of these integral membrane proteins form macromolecular signaling complexes by physically associating with many other proteins. These macromolecular signaling complexes ensure specificity and proper rates of signal transduction. The large-conductance, Ca(2+)-activated K(+) (BK) channel is dually activated by membrane depolarization and increases in intracellular free Ca(2+) ([Ca(2+)](i)). The activation of BK channels results in a large K(+) efflux and, consequently, rapid membrane repolarization and closing of the voltage-dependent Ca(2+)-permeable channels to limit further increases in [Ca(2+)](i). Therefore, BK channel-mediated K(+) signaling is a negative feedback regulator of both membrane potential and [Ca(2+)](i) and plays important roles in many physiological processes and diseases. However, the BK channel formed by the pore-forming and voltage- and Ca(2+)-sensing α subunit alone requires high [Ca(2+)](i) levels for channel activation under physiological voltage conditions. Thus, most native BK channels are believed to co-localize with Ca(2+)-permeable channels within nanodomains (a few tens of nanometers in distance) to detect high levels of [Ca(2+)](i) around the open pores of Ca(2+)-permeable channels. Over the last two decades, advancement in research on the BK channel’s coupling with Ca(2+)-permeable channels including recent reports involving NMDA receptors demonstrate exemplary models of nanodomain structural and functional coupling among ion channels for efficient signal transduction and negative feedback regulation. We hereby review our current understanding regarding the structural and functional coupling of BK channels with different Ca(2+)-permeable channels. |
format | Online Article Text |
id | pubmed-8795833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87958332022-01-29 Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes Shah, Kunal R. Guan, Xin Yan, Jiusheng Front Physiol Physiology Biochemical and functional studies of ion channels have shown that many of these integral membrane proteins form macromolecular signaling complexes by physically associating with many other proteins. These macromolecular signaling complexes ensure specificity and proper rates of signal transduction. The large-conductance, Ca(2+)-activated K(+) (BK) channel is dually activated by membrane depolarization and increases in intracellular free Ca(2+) ([Ca(2+)](i)). The activation of BK channels results in a large K(+) efflux and, consequently, rapid membrane repolarization and closing of the voltage-dependent Ca(2+)-permeable channels to limit further increases in [Ca(2+)](i). Therefore, BK channel-mediated K(+) signaling is a negative feedback regulator of both membrane potential and [Ca(2+)](i) and plays important roles in many physiological processes and diseases. However, the BK channel formed by the pore-forming and voltage- and Ca(2+)-sensing α subunit alone requires high [Ca(2+)](i) levels for channel activation under physiological voltage conditions. Thus, most native BK channels are believed to co-localize with Ca(2+)-permeable channels within nanodomains (a few tens of nanometers in distance) to detect high levels of [Ca(2+)](i) around the open pores of Ca(2+)-permeable channels. Over the last two decades, advancement in research on the BK channel’s coupling with Ca(2+)-permeable channels including recent reports involving NMDA receptors demonstrate exemplary models of nanodomain structural and functional coupling among ion channels for efficient signal transduction and negative feedback regulation. We hereby review our current understanding regarding the structural and functional coupling of BK channels with different Ca(2+)-permeable channels. Frontiers Media S.A. 2022-01-14 /pmc/articles/PMC8795833/ /pubmed/35095560 http://dx.doi.org/10.3389/fphys.2021.796540 Text en Copyright © 2022 Shah, Guan and Yan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Shah, Kunal R. Guan, Xin Yan, Jiusheng Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes |
title | Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes |
title_full | Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes |
title_fullStr | Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes |
title_full_unstemmed | Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes |
title_short | Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes |
title_sort | structural and functional coupling of calcium-activated bk channels and calcium-permeable channels within nanodomain signaling complexes |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795833/ https://www.ncbi.nlm.nih.gov/pubmed/35095560 http://dx.doi.org/10.3389/fphys.2021.796540 |
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