Increased Intracellular Calcium Causes Ventricular Electrical Turbulences And Arrhythmias In The Heart

Background: Dysregulation of intracellular Ca²⁺ homeostatsis is associated with pathological conditions and the arrhythmogenesis of the heart. The objective of this study was to investigate the effects of acute increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i), mimicking intracellular Ca²⁺ overload, on cellular electrophysiology of guinea pig ventricular myocytes.Methods: Myocytes were isolated enzymatically from guinea pig hearts. [Ca²⁺]_i was clamped to either a control (65-100nmol/L) or increased level (1μmol/L). Transmembrane action potentials (AP) and ionic currents were recorded using whole cell current and voltage clamp techniques.Results: Compared with the control, acute increased [Ca²⁺]_i shortened action potential duration (APD), decreased action potential amplitude (APA) and maximal depolarization velocity (Vmax), and resting membrane potential (RMP), and caused delayed afterdepolarizations (DADs) and triggered activities in 5 and 3 out of 15 cells. Acute increased [Ca²⁺]_i regulates peak and late INa, IKr, ICaL and IK1 but not IKs and the effects reached steady-states at 5-8 min. Increased [Ca²⁺]_i time-dependently increased peak and late INa (n=8 and 7, p<0.01) and shifted steady-state inactivation, but not the activation, of the peak INa toward to the more positive potential. Increased [Ca²⁺]_i decreased ICaL at 1 and 5 min (n=7, p<0.01) and IK1 (n=8, p<0.01), and increased IKr (n=7, p<0.01) but not IKs (n=7, p>0.05) at 2-8 min.Conclusion: Acute increased [Ca²⁺]_i regulated various cardiac ionic currents, decreased RMP, APA, Vmax and APD, and caused arrhythmic activities. These results can be used to explain the calcium overload-induced ventricular arrhythmias in clinical and experimental observations.