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

Dysregulation of intracellular Ca(2+) 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 Ca(2+) concentration ([Ca(2+)](i)) on the electrophysiology of ventricular myocytes by mimicking intracellular Ca(2+) overload. The [Ca(2+)](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 [Ca(2+)](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 [Ca(2+)](i) augmented late I (Na) in a time-dependent manner, reduced I (CaL) and I (K1), and increased I (Kr) but not I (Ks). The results of this study can be used to explain calcium overload-induced ventricular arrhythmias.