Increased GIRK channel activity prevents arrhythmia in mice with heart failure by enhancing ventricular repolarization.

ABSTRACT: Ventricular arrhythmia causing sudden cardiac death is the leading mode of death in patients with heart failure. Yet, the mechanisms that prevent ventricular arrhythmias in heart failure are not well characterized. Using a mouse model of heart failure created by transverse aorta constriction, we show that GIRK channel, an important regulator of cardiac action potentials, is constitutively active in failing ventricles in contrast to normal cells. Evidence is presented indicating that the tonic activation of M₂ muscarinic acetylcholine receptors by endogenously released acetylcholine contributes to the constitutive GIRK activity. This constitutive GIRK activity prevents the action potential prolongation in heart failure ventricles. Consistently, GIRK channel blockade with tertiapi

SUBMITTER: An X 

PROVIDER: S-EPMC10728207 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature