Changes of action potential in human papillary muscles by methoxyverapamil

The effects of Ca-antagonist methoxyverapamil (MOV) on the action potential and force of contraction (Fc) were studied on isolated human papillary muscles driven by electrical stimuli. In the control, the resting potential (RP) was - 83.6±2.9 mV, action potential duration (APD) at 90% of repolarization (APD90 ) 338±80 ms, and maximal upstroke velocity of action potential (dV/dtmax) 204±52 V/s. At 10-5 M MOV depressed Fc, APD20 and APD90 to 9%, 69% and 88% of the control values, respectively. But RP and dV/dtmax were not changed. MOV diminished Fc and APD in a concentration- and frequency-dependent way, but RP and dV/dtmax were not changed not only by 10-9-10-5 M but also at 0.1-5.0 Hz of stimuli. The results show that the negative inotropic effect of MOV and the shortened APD by MOV can be explained by depression of Ca2+ slow inward current during the cardiac action potential, but dV/dtmax was not changed by MOV, since Ca-antagonist does not affect the fast Na+ inward current.