Voltage-dependent modulation of Ca channel current in heart cells by Bay K8644.
We have investigated the voltage-dependent effects of the dihydropyridine Bay K8644 on Ca channel currents in calf Purkinje fibers and enzymatically dispersed rat ventricular myocytes. Bay K8644 increases the apparent rate of inactivation of these currents, measured during depolarizing voltage pulses, and shifts both channel activation and inactivation in the hyperpolarizing direction. Consequently, currents measured after hyperpolarizing conditioning pulses are larger in the presence of drug compared with control conditions, but are smaller than control if they are measured after positive conditioning pulses. Most of our experimental observations on macroscopic currents can be explained by a single drug-induced change in one rate constant of a simple kinetic model. The rate constant change is consistent with results obtained by others with single channel recordings.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002417:Cattle; D004553:Electric Conductivity; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D015737:Nisoldipine; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D016276:Ventricular Function
D002121:Calcium Channel Blockers; D007473:Ion Channels; D015737:Nisoldipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium