EFFECTS OF CAPTOPRIL ON MEMBRANE CURRENT AND CONTRACTION IN SINGLE VENTRICULAR MYOCYTES FROM GUINEA-PIG

1 Single guinea-pig ventricular myocytes were voltage-clamped and cell length was measured with a photodiode array. 2 Captopril (1 x 10(-5) M) reduced both peak early current and active shortening in response to a depolarizing clamp pulse along a similar time course. 3 From a holding potential of around -45 mV peak early inward current was reduced by 37 +/- 9% (P < 0.001) on exposure to captopril. The early current-voltage relationship was shifted outwards by captopril indicating a reduction in membrane conductance through the L-type calcium channel (I(Ca)). 4 The amplitude of cell shortening in response to depolarizing voltage steps was reduced but the voltage-dependence of contraction after captopril was unchanged. 5 A small negative shift of the potential at which I(Ca) was half-activated was observed after captopril. There was no change in the voltage-dependence of the inactivation variable or in the time-dependence of repriming for I(Ca). 6 The actions of captopril on I(Ca) and developed shortening were dose-dependent and took place in the same proportion when I(Ca) was increased by isoprenaline. 7 These results are discussed in relation to the effects of captopril on I(Ca) and contraction and to its clinical usage.