Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium

Abstract

In order to elucidate the mode of action of the Ca²⁺-antagonistic inhibitor nifedipine, its effect on Ca²⁺-mediated action potentials and transmembrane slow inward current in papillary muscles of guinea pigs and cats was studied. Nifedipine (0.5 mg/l≈1.4×10⁻⁶M) depressed upstroke velocity and overshoot of the Ca²⁺-mediated action potential and reduced the transmembrane slow inward current by about 50%, but the kinetics of inactivation and recovery from inactivation were not affected. The decrease of upstroke velocity was accompanied by a proportional diminution of isometric contractile force. This indicates that nifedipine exerts its Ca²⁺-antagonistic effect on excitation-contraction coupling in mammalian ventricular myocardium by inhibition of the transmembrane Ca²⁺ inward current. The inhibitory action of nifedipine on contractile tension development could be neutralized by an augmentation of the extracellular Ca²⁺ concentration from 2 mM to 4 mM or by β-receptor stimulation (isoproterenol) that promotes the transmembrane Ca²⁺-rich medium or under the influence of isoproterenol the upstroke velocity of the Ca²⁺-mediated action potentials rose even above the initial values which were measured prior to the nifedipine administration.