Age-related Quinidine Effects on Ionic Currents of Rabbit Cardiac Myocytes

Abstract

Age-related cardiac actions of quinidine have been shown in prolongation of action potential duration, but not in the tonic and use-dependent block of the maximal velocity of action potential upstroke. To elucidate the underlying ionic mechanisms, currents through the Na, Ca and K channels were examined by using a whole-cell voltage clamp technique on isolated neonatal (<5 day) and adult (>3 months) rabbit cardiac myocytes under various concentrations (0.5, 1.5 and 4.5 μM) of quinidine. In neonatal and adult myocytes, quinidine caused a comparable degree of dose-dependent effects on Na currents including decrease in peak Na currents, left-shift of steady-state availability curve and slowing of the recovery from inactivation. However, the inwardly rectifier K current and the transient outward current were suppressed to a greater extent in the neonatal myocytes than in the adult ( P=0.0002 and 0.02, respectively). On the contrary, the magnitude of decrease in peak Ca currents after quinidine treatment was much smaller in the neonatal myocytes than in the adult ( P=0.01). These findings indicate that age-related ionic channel-block by quinidine is complex; and shows major differences in the Ca and K currents of cardiac myocytes. Accordingly, a differential therapeutic potential of quinidine may exist in hearts of different ages.