Variable effects of isoproterenol on action potential duration in guinea-pig papillary muscle: differences between nonsteady and steady state; role of extracellular calcium concentration.

The effect of three different isoproterenol (ISP) concentrations (10(-6), 10(-7) and 10(-8) M) on action potential duration (APD) was studied in guinea-pig papillary muscles at low (0.6-0.9 mM), intermediate (1.8 mM) and high (3.6 mM) calcium concentrations (Ca++)0. All three ISP concentrations produced (Ca++)0-dependent changes during both nonsteady (NSS) and steady state (SS). During NSS, initial prolongation of APD occurred in 22 of 22 experiments at low, in 16 of 36 experiments at intermediate and 0 of 15 experiments at high (Ca++)0. In the remaining experiments, APD became progressively shorter. The NSS-APD changes were associated with increase in plateau amplitude attributed to slow inward current (isi). However, we found no correlation between the amplitude of plateau and APD change. This suggests that the (Ca++)0-dependent differences were due more likely to differences in the rat of isi inactivation than to differences in the absolute isi magnitude. The SS-APD was also dependent on (Ca++)0 but, during progression from NSS to SS, plateau amplitude did not change, whereas the force of contraction increased. This supports the hypothesis that the dependence of SS-APD on (Ca++)0 is mediated by the time-independent K conductance controlled by intracellular calcium concentration. Thus, the early and the late ISP effects on APD appeared to differ in their mechanism, but both depended on (Ca++)0.