Distinctive electrophysiological characteristics of right ventricular out-flow tract cardiomyocytes

Abstract

Ventricular arrhythmias commonly originate from the right ventricular out-flow tract (RVOT). However, the electrophysiological characteristics and Ca2+ homoeostasis of RVOT cardiomyocytes remain unclear. Whole-cell patch clamp and indo-1 fluorometric ratio techniques were used to investigate action potentials, Ca2+ homoeostasis and ionic currents in isolated cardiomyocytes from the rabbit RVOT and right ventricular apex (RVA). Conventional microelectrodes were used to record the electrical activity before and after (KN-93, a Ca2+/calmodulin-dependent kinase II inhibitor, or ranolazine, a late sodium current inhibitor) treatment in RVOT and RVA tissue preparations under electrical pacing and ouabain (Na+/K+ ATPase inhibitor) administration. In contrast to RVA cardiomyocytes, RVOT cardiomyocytes were characterized by longer action poten-tial duration measured at 90 % and 50 % repolarization, larger Ca2+ transients, higher Ca2+ stores, higher late Na+ and transient outward K+ cur-rents, but smaller delayed rectifier K+, L-type Ca2+ currents and Na+-Ca2+ exchanger currents. RVOT cardiomyocytes showed significantly more pacing-induced delayed afterdepolarizations (22 % versus 0%, P < 0.05) and ouabain-induced ventricular arrhythmias (94 % versus 61%