Effects of prenylamine on cardiac membrane currents and contractility.
The influence of prenylamine on the electrical and mechanical activity of frog atrial muscle fibers has been studied under voltage clamp conditions. At a concentration of 10-4 M, prenylamine blocks the action potential without much affecting the resting potential. The drug depresses the peak transient sodium conductance with a dissociation constant of 1.7 times 10-5 M and on a one-to-one stoichiometric basis. The curve relating peak sodium conductance to membrane potential is slightly shifted in the direction of hyperpolarization. The time to peak sodium current and the rate of sodium inactivation are not significantly altered. With 2 times 10-5 M prenylamine, the steady-state sodium inactivation curve is shifted by 5 mV to more negative membrane potentials but the decreased availability of the sodium system at the resting level is not sufficient to account for the reduction of sodium current. Recovery from sodium inactivation upon repolarization is distinctly slowed. The slow (secondary) inward current carried by calcium and/or sodium and the steady-state outward current are also depressed by prenylamine. The phasic (twitch-like) contraction related to the slow inward current is slightly decreased. The tonic (sustained) contraction associated with long-lasting depolarizations is increased and the time course of relaxation is retarded by prenylamine.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D011299:Prenylamine / Q000494:pharmacology*; D011892:Rana catesbeiana; D012964:Sodium / Q000502:physiology
D012964:Sodium; D011299:Prenylamine; D002118:Calcium