The role of calcium current and changes in intracellular calcium concentration ([Ca2+l,) in regulation of action potential duration (APD) during electrical restitution process was studied in mammalian ventricular preparations. Properly timed action potentials were recorded from multicellular preparations and isolated cardiomyocytes using conventional microelectrodes and EGTA-containing patch pipettes. APD increased monotonically in canine and guinea pig ventricular preparations with increasing diestolic interval (DI), while in rabbit papillary muscles the restitution process was biphasic: APD first lengthened, then shortened as the DI increased. When the restitution process was studied in single cardiomyocytes using EGTA-containing patch pipettes, the restitution pattern was similar in the three species studied. Similarly, no difference was observed in the recovery time constant of calcium current (I(ca)-L) measured under these conditions in voltage clamped myocytes. Loading the myocytes with the [Ca2+](i)-chelator BAPTA-AM had adverse effects in rabbit and canine cells. In rabbit myocytes steady-state APD lengthened and the late shortening component of restitution was abolished in BAPTA-loaded cells. In canine myocytes BAPTA-load shortened steady-state APD markedly, and during restitution, APD decreased with increasing DI. The late shortening component of restitution, observed in untreated rabbit preparations, was greatly reduced after nifedipine treatment, but remained preserved in the presence of 4-aminopyridine or nicorandil. Beat to beat changes in APD, peak I(Ca)-L and [Ca2+](i), measured using the fluorescent dye, Fura-2, were monitored in rabbit ventricular myocytes after a 1-min period of rest. In these cells, the shortening of APD was accompanied by a gradual reduction of the peak I(Ca)-L and elevation of diastolic (Ca2+](i) during the initial eight post-rest action potentials. It is concluded that elevation of [Ca2+](i) shortens, while reduction of [Ca2+](i) lengthens APD in rabbit, but not in canine ventricular myocytes. These differences may probably be related to different distributions of [Ca2+](i)-dependent ion currents and/or to differences in calcium handling between the two species.
ASJC Scopus subject areas