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Functional Regulation of K(ATP) Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases

ATP-sensitive potassium channels (K(ATP) channels) play pivotal roles in excitable cells and link cellular metabolism with membrane excitability. The action potential converts electricity into dynamics by ion channel-mediated ion exchange to generate systole, involved in every heartbeat. Activation...

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Autores principales: Wang, Zhicheng, Bian, Weikang, Yan, Yufeng, Zhang, Dai-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274113/
https://www.ncbi.nlm.nih.gov/pubmed/35837280
http://dx.doi.org/10.3389/fphar.2022.868401
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author Wang, Zhicheng
Bian, Weikang
Yan, Yufeng
Zhang, Dai-Min
author_facet Wang, Zhicheng
Bian, Weikang
Yan, Yufeng
Zhang, Dai-Min
author_sort Wang, Zhicheng
collection PubMed
description ATP-sensitive potassium channels (K(ATP) channels) play pivotal roles in excitable cells and link cellular metabolism with membrane excitability. The action potential converts electricity into dynamics by ion channel-mediated ion exchange to generate systole, involved in every heartbeat. Activation of the K(ATP) channel repolarizes the membrane potential and decreases early afterdepolarization (EAD)-mediated arrhythmias. K(ATP) channels in cardiomyocytes have less function under physiological conditions but they open during severe and prolonged anoxia due to a reduced ATP/ADP ratio, lessening cellular excitability and thus preventing action potential generation and cell contraction. Small active molecules activate and enhance the opening of the K(ATP) channel, which induces the repolarization of the membrane and decreases the occurrence of malignant arrhythmia. Accumulated evidence indicates that mutation of K(ATP) channels deteriorates the regulatory roles in mutation-related diseases. However, patients with mutations in K(ATP) channels still have no efficient treatment. Hence, in this study, we describe the role of K(ATP) channels and subunits in angiocardiopathy, summarize the mutations of the K(ATP) channels and the functional regulation of small active molecules in K(ATP) channels, elucidate the potential mechanisms of mutant K(ATP) channels and provide insight into clinical therapeutic strategies.
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spelling pubmed-92741132022-07-13 Functional Regulation of K(ATP) Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases Wang, Zhicheng Bian, Weikang Yan, Yufeng Zhang, Dai-Min Front Pharmacol Pharmacology ATP-sensitive potassium channels (K(ATP) channels) play pivotal roles in excitable cells and link cellular metabolism with membrane excitability. The action potential converts electricity into dynamics by ion channel-mediated ion exchange to generate systole, involved in every heartbeat. Activation of the K(ATP) channel repolarizes the membrane potential and decreases early afterdepolarization (EAD)-mediated arrhythmias. K(ATP) channels in cardiomyocytes have less function under physiological conditions but they open during severe and prolonged anoxia due to a reduced ATP/ADP ratio, lessening cellular excitability and thus preventing action potential generation and cell contraction. Small active molecules activate and enhance the opening of the K(ATP) channel, which induces the repolarization of the membrane and decreases the occurrence of malignant arrhythmia. Accumulated evidence indicates that mutation of K(ATP) channels deteriorates the regulatory roles in mutation-related diseases. However, patients with mutations in K(ATP) channels still have no efficient treatment. Hence, in this study, we describe the role of K(ATP) channels and subunits in angiocardiopathy, summarize the mutations of the K(ATP) channels and the functional regulation of small active molecules in K(ATP) channels, elucidate the potential mechanisms of mutant K(ATP) channels and provide insight into clinical therapeutic strategies. Frontiers Media S.A. 2022-06-28 /pmc/articles/PMC9274113/ /pubmed/35837280 http://dx.doi.org/10.3389/fphar.2022.868401 Text en Copyright © 2022 Wang, Bian, Yan and Zhang. 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 Pharmacology
Wang, Zhicheng
Bian, Weikang
Yan, Yufeng
Zhang, Dai-Min
Functional Regulation of K(ATP) Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases
title Functional Regulation of K(ATP) Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases
title_full Functional Regulation of K(ATP) Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases
title_fullStr Functional Regulation of K(ATP) Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases
title_full_unstemmed Functional Regulation of K(ATP) Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases
title_short Functional Regulation of K(ATP) Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases
title_sort functional regulation of k(atp) channels and mutant insight into clinical therapeutic strategies in cardiovascular diseases
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274113/
https://www.ncbi.nlm.nih.gov/pubmed/35837280
http://dx.doi.org/10.3389/fphar.2022.868401
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