Expression and relevance of the G protein-gated K+ channel in the mouse ventricle

Abstract The atrial G protein-gated inwardly rectifying K+ (GIRK) channel is a critical mediator of parasympathetic influence on cardiac physiology. Here, we probed the details and relevance of the GIRK channel in mouse ventricle. mRNAs for the atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscari...

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Autores principales:	Allison Anderson, Kanchan Kulkarni, Ezequiel Marron Fernandez de Velasco, Nicholas Carlblom, Zhilian Xia, Atsushi Nakano, Kirill A. Martemyanov, Elena G. Tolkacheva, Kevin Wickman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/88e26c9be7d64664993ca42a8ef00461
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spelling	oai:doaj.org-article:88e26c9be7d64664993ca42a8ef004612021-12-02T15:08:14ZExpression and relevance of the G protein-gated K+ channel in the mouse ventricle10.1038/s41598-018-19719-x2045-2322https://doaj.org/article/88e26c9be7d64664993ca42a8ef004612018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19719-xhttps://doaj.org/toc/2045-2322Abstract The atrial G protein-gated inwardly rectifying K+ (GIRK) channel is a critical mediator of parasympathetic influence on cardiac physiology. Here, we probed the details and relevance of the GIRK channel in mouse ventricle. mRNAs for the atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscarinic receptor (M2R), and RGS6, a negative regulator of atrial GIRK-dependent signaling, were detected in mouse ventricle at relatively low levels. The cholinergic agonist carbachol (CCh) activated small GIRK currents in adult wild-type ventricular myocytes that exhibited relatively slow kinetics and low CCh sensitivity; these currents were absent in ventricular myocytes from Girk1−/− or Girk4−/− mice. While loss of GIRK channels attenuated the CCh-induced shortening of action potential duration and suppression of ventricular myocyte excitability, selective ablation of GIRK channels in ventricle had no effect on heart rate, heart rate variability, or electrocardiogram parameters at baseline or after CCh injection. Additionally, loss of ventricular GIRK channels did not impact susceptibility to ventricular arrhythmias. These data suggest that the mouse ventricular GIRK channel is a GIRK1/GIRK4 heteromer, and show that while it contributes to the cholinergic suppression of ventricular myocyte excitability, this influence does not substantially impact cardiac physiology or ventricular arrhythmogenesis in the mouse.Allison AndersonKanchan KulkarniEzequiel Marron Fernandez de VelascoNicholas CarlblomZhilian XiaAtsushi NakanoKirill A. MartemyanovElena G. TolkachevaKevin WickmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Allison Anderson Kanchan Kulkarni Ezequiel Marron Fernandez de Velasco Nicholas Carlblom Zhilian Xia Atsushi Nakano Kirill A. Martemyanov Elena G. Tolkacheva Kevin Wickman Expression and relevance of the G protein-gated K+ channel in the mouse ventricle
description	Abstract The atrial G protein-gated inwardly rectifying K+ (GIRK) channel is a critical mediator of parasympathetic influence on cardiac physiology. Here, we probed the details and relevance of the GIRK channel in mouse ventricle. mRNAs for the atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscarinic receptor (M2R), and RGS6, a negative regulator of atrial GIRK-dependent signaling, were detected in mouse ventricle at relatively low levels. The cholinergic agonist carbachol (CCh) activated small GIRK currents in adult wild-type ventricular myocytes that exhibited relatively slow kinetics and low CCh sensitivity; these currents were absent in ventricular myocytes from Girk1−/− or Girk4−/− mice. While loss of GIRK channels attenuated the CCh-induced shortening of action potential duration and suppression of ventricular myocyte excitability, selective ablation of GIRK channels in ventricle had no effect on heart rate, heart rate variability, or electrocardiogram parameters at baseline or after CCh injection. Additionally, loss of ventricular GIRK channels did not impact susceptibility to ventricular arrhythmias. These data suggest that the mouse ventricular GIRK channel is a GIRK1/GIRK4 heteromer, and show that while it contributes to the cholinergic suppression of ventricular myocyte excitability, this influence does not substantially impact cardiac physiology or ventricular arrhythmogenesis in the mouse.
format	article
author	Allison Anderson Kanchan Kulkarni Ezequiel Marron Fernandez de Velasco Nicholas Carlblom Zhilian Xia Atsushi Nakano Kirill A. Martemyanov Elena G. Tolkacheva Kevin Wickman
author_facet	Allison Anderson Kanchan Kulkarni Ezequiel Marron Fernandez de Velasco Nicholas Carlblom Zhilian Xia Atsushi Nakano Kirill A. Martemyanov Elena G. Tolkacheva Kevin Wickman
author_sort	Allison Anderson
title	Expression and relevance of the G protein-gated K+ channel in the mouse ventricle
title_short	Expression and relevance of the G protein-gated K+ channel in the mouse ventricle
title_full	Expression and relevance of the G protein-gated K+ channel in the mouse ventricle
title_fullStr	Expression and relevance of the G protein-gated K+ channel in the mouse ventricle
title_full_unstemmed	Expression and relevance of the G protein-gated K+ channel in the mouse ventricle
title_sort	expression and relevance of the g protein-gated k+ channel in the mouse ventricle
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/88e26c9be7d64664993ca42a8ef00461
work_keys_str_mv	AT allisonanderson expressionandrelevanceofthegproteingatedkchannelinthemouseventricle AT kanchankulkarni expressionandrelevanceofthegproteingatedkchannelinthemouseventricle AT ezequielmarronfernandezdevelasco expressionandrelevanceofthegproteingatedkchannelinthemouseventricle AT nicholascarlblom expressionandrelevanceofthegproteingatedkchannelinthemouseventricle AT zhilianxia expressionandrelevanceofthegproteingatedkchannelinthemouseventricle AT atsushinakano expressionandrelevanceofthegproteingatedkchannelinthemouseventricle AT kirillamartemyanov expressionandrelevanceofthegproteingatedkchannelinthemouseventricle AT elenagtolkacheva expressionandrelevanceofthegproteingatedkchannelinthemouseventricle AT kevinwickman expressionandrelevanceofthegproteingatedkchannelinthemouseventricle
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Expression and relevance of the G protein-gated K+ channel in the mouse ventricle

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