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 less than 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 (ICa). 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 ICa 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 ICa. 6. The actions of captopril on ICa and developed shortening were dose-dependent and took place in the same proportion when Ica was increased by isoprenaline. 7. These results are discussed in relation to the effects of captopril on Ica and contraction and to its clinical usage.
Bryant
S M
SM
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington.
Ryder
K O
KO
Hart
G
G
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects
D015220:Calcium Channels; D002216:Captopril