INTRACELLULAR CALCIUM AND ELECTRICAL RESTITUTION IN MAMMALIAN CARDIAC-CELLS

The role of calcium current and changes in intracellular calcium conce ntration ([Ca2+](i)) in regulation of action potential duration (APD) during electrical restitution process was studied in mammalian ventric ular preparations. Properly timed action potentials were recorded from multicellular preparations and isolated cardiomyocytes using conventi onal microelectrodes and EGTA-containing patch pipettes, APD increased monotonically in canine and guinea pig ventricular preparations with increasing diastolic interval (DI), while in rabbit papillary muscles the restitution process was biphasic: APD first lengthened, then short ened as the DI increased. When the restitution process was studied in single cardiomyocytes using EGTA-containing patch pipettes, the restit ution pattern was similar in the three species studied. Similarly, no difference was observed in the recovery time constant of calcium curre nt (/(Ca-L)) measured under these conditions in voltage clamped myocyt es. Loading the myocytes with the [Ca2+](i)-chelator BAPTA-AM had adve rse effects in rabbit and canine cells. In rabbit myocytes steady-stat e APD lengthened and the late shortening component of restitution was abolished in BAPTA-loaded cells. In canine myocytes BAPTA-load shorten ed steady-stare APD markedly, and during restitution, APD decreased wi th increasing DI. The late shortening component of restitution, observ ed in untreated rabbit preparations, was greatly reduced after nifedip ine treatment, but remained preserved in the presence of 4-aminopyridi ne or nicorandil. Beat to beat changes in APD, peak /Ca-L and [Ca2+](i ), measured using the fluorescent dye, Fura-2, were monitored in rabbi t ventricular myocytes after a 1-min period of rest. In these cells, t he shortening of APD was accompanied by a gradual reduction of the pea k /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.io different distributions of [Ca2+](i)-dependent ion current s and/or to differences in calcium handling between the two species.