Changes in intracellular calcium concentration influence beat-to-beat variability of action potential duration in...

The aim of the present work was to study the influence of changes in intracellular calcium concentration ([Ca(2+)]i) on beat-to-beat variability (short term variability, SV) of action potential duration (APD) in isolated canine ventricular cardiomyocytes. Series of action potentials were recorded from enzymatically isolated canine ventricular cells using conventional microelectrode technique. Drug effects on SV were evaluated as relative SV changes determined by plotting the drug-induced changes in SV against corresponding changes in APD and comparing these data to the exponential SV-APD function obtained with inward and outward current injections. Exposure of myocytes to the Ca(2+) chelator BAPTA-AM (5 μM) decreased, while Ca(2+) ionophore A23187 (1 μM) increased the magnitude of relative SV. Both effects were primarily due to the concomitant changes in APD. Relative SV was reduced by BAPTA-AM under various experimental conditions including pretreatment with veratridine, BAY K8644, dofetilide or E-4031. Contribution of transient changes of [Ca(2+)]i due to Ca(2+) released from the sarcoplasmic reticulum (SR) was studied using 10 μM ryanodine and 1 μM cyclopiazonic acid: relative SV was reduced by both agents. Inhibition of the Na(+)-Ca(2+) exchanger by 1 μM SEA0400 increased relative SV. It is concluded that elevation of [Ca(2+)]i increases relative SV significantly. More importantly, Ca(2+) released from the SR is an important component of this effect.