Increased intracellular calcium concentration causes electrical turbulence in guinea pig ventricular myocytes

Abstract

Dysregulation of intracellular Ca2+ homeostasis is associated with various pathological conditions and arrhythmogenesis of the heart. The objective of this study was to investigate the effects of an acute increase in intracellular Ca2+ concentration ([Ca2+]i) on the electrophysiology of ventricular myocytes by mimicking intracellular Ca2+ overload. The [Ca2+]i was clamped to either a controlled (65-100 nmol L-1) or increased (1 μmol L-1) level. The transmembrane action potentials and ionic currents were recorded using whole-cell patch clamp techniques. We found that the acute increase in [Ca2+]i shortened the action potential duration, reduced the action potential amplitude, maximum depolarization velocity and resting membrane potential, caused delayed after-depolarizations (DADs), and triggered activity-compared with these parameters in the control. The increased [Ca2+]i augmented late INa in a time-dependent manner, reduced ICaL and IK1, and increased IKr but not IKs. The results of this study can be used to explain calcium overload-induced ventricular arrhythmias. © 2011 The Author(s).