Résumé
The effect of three well known calcium antagonists [verapamil, diltiazem and nifedipine] on the force of contraction of left guinea-pig atria and on the physicochemical properties of differently composed liposomes was investigated at three external calcium concentrations. The physicochemical properties of liposomes were assessed by the drug-induced change in the surface potential measured by laser Doppler electrophoresis. High calcium concentrations cause a shift in the calcium antagonist concentration-response curves performed in experiments on the force of contraction as well as on the membrane surface potential. The calcium induced shift was highest for verapamil and lowest for nifedipine. The same sequence was observed for the drug-induced surface potential change on liposomes; nifedipine, an uncharged molecule at physiological pH had no effect at all. The sequence of drug receptor affinities, however, was as follows: Nifedipine > verapamil > diltiazem. It may be concluded that charged molecules like verapamil and diltiazem exert their negative inotropic action via two mechanisms; namely, a calcium channel blockade and a change in the electrostatic potential of the membrane, while nifedipine acts only via its calcium blocking activity