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

Allison Anderson, Kanchan Kulkarni, Ezequiel Marron Fernandez De Velasco, Nicholas Carlblom, Zhilian Xia, Atsushi Nakano, Kirill A. Martemyanov, Elena G. Tolkacheva, Kevin Wickman

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 (M 2 R), 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.

Original languageEnglish (US)
Article number1192
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Inwardly Rectifying Potassium Channel
GTP-Binding Proteins
Carbachol
Muscle Cells
Heart Rate
Muscarinic M2 Receptors
Cholinergic Agonists
protein K
Cholinergic Agents
Action Potentials
Cardiac Arrhythmias
Electrocardiography
Messenger RNA
Injections

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Expression and relevance of the G protein-gated K + channel in the mouse ventricle . / Anderson, Allison; Kulkarni, Kanchan; Marron Fernandez De Velasco, Ezequiel; Carlblom, Nicholas; Xia, Zhilian; Nakano, Atsushi; Martemyanov, Kirill A.; Tolkacheva, Elena G.; Wickman, Kevin.

In: Scientific reports, Vol. 8, No. 1, 1192, 01.12.2018.

Research output: Contribution to journalArticle

Anderson, Allison ; Kulkarni, Kanchan ; Marron Fernandez De Velasco, Ezequiel ; Carlblom, Nicholas ; Xia, Zhilian ; Nakano, Atsushi ; Martemyanov, Kirill A. ; Tolkacheva, Elena G. ; Wickman, Kevin. / Expression and relevance of the G protein-gated K + channel in the mouse ventricle In: Scientific reports. 2018 ; Vol. 8, No. 1.
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