Effects of a Selective Acetylcholine-activated Potassium Channel Blocker on the Regulation of Heart Rate

Abstract

Sinus bradycardia causes a decreased cardiac output resulting in a variety of clinical symptoms. From a pedigree of familial sinus bradycardia, we previously identified a novel missense mutation in the KCNJ3 gene. KCNJ3 is a member of heterotetrameric acetylcholine-activated potassium channel (KACh channel) in the sinus node, atrioventricular node, and atrial myocardium. The mutation is located in the M1 helix of KCNJ3, which forms the transmembrane pore of the KACh channel. Electrophysiological analyses demonstrated that the KCNJ3 mutation increased the basal current amplitude, and the increased current flow through KACh channels leads to sinus bradycardia.