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

TLDR: In this paper, Nifedipine (0.5 mg/1 approximately 1.4 X 10(-6) M) 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.

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/1 approximately 1.4 X 10(-6) M) 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 beta-receptor stimulation (isoproterenol) that promotes the transmembrane Ca2+ uptake during excitation. Simultaneously, in the 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.