Calcium-dependent electrophysiological alterations in hypertrophied rat cardiomyocytes

We compared the occurrence of calcium-dependent electrophysiological alterations in left ventricular myocytes isolated from the heart of old spontaneously hypertensive (SHR) and age-matched normotensive Wistar Kyoto rats (WKY). Electrical and mechanical activity were measured in patch-clamped myocytes in which intracellular Ca2+ was allowed to change freely. In parallel experiments, intracellular Ca2+ concentration was monitored in fura-2-AM preloaded cells using an image analysis system. Left ventricular myocytes from SHR showed a significantly greater membrane capacitance (an index of cell size), a prolonged duration of the action potential and a higher incidence of delayed afterdepolarization (DADs) and associated aftercontractions, and of spontaneous activity. DADs were likely generated by intracellular Ca2+ waves due to spontaneous and local Ca2+ release from intracellular stores. These results demonstrate that DADs, possibly related to spontaneous intracellular Ca2+ waves, occur frequently in hypertrophied rat cardiomyocytes and may be a relevant arrhythmogenic mechanism.