Calcium current and tension generation in immature mammalian myocardium: Effects of diltiazem

Abstract

Single sucrose gap and isolated myocyte voltage-clamp techniques were used to study the effects of diltiazem on calcium current ( I Ca) and tension generation in isolated ventricular myocytes and right ventricular papillary muscles from neonatal New Zealand White rabbits. Diltiazem was shown to significantly shorten the duration of isolated myocyte action potentials with no effect on overshoot potential or resting membrane potential. Diltiazem blocked but did not completely abolish I Ca in these neonatal cells. Addition of diltiazem to the solution bathing papillary muscles resulted in a similar reduction in action potential duration accompanied by a reduction in twitch tension. When the duration of depolarization was controlled employing the single sucrose gap voltage clamp, the decrease in tension development caused by diltiazem was abolished despite a significant decrease in twitch tension in the same muscles. In another series of experiments it was demonstrated that the magnitude of developed tension in neonatal papillary muscles is dependent upon the duration of depolarization. Taken together, the results of this investigation suggest that in neonatal myocardium when I Ca is blocked by diltiazem, the resulting reduction in developed tension is caused in part by reduction of action potential duration. The calcium carried into the neonatal heart cell by I Ca does not appear to be the only source of extracellular Ca 2+ for excitation-contraction coupling. Finally, the action potential appears to act as a gate for calcium movement into the neonatal heart cell.