Effects of the calcium antagonist diltiazem on action potentials, slow response and force of contraction in different cardiac tissues.
Action potential duration in human and guinea-pig ventricular myocardium is reduced by diltiazem greater than or equal to 10 mumol/l. A reduction of action potential amplitude and maximum upstroke velocity is observed only at high concentrations of diltiazem (30 mumol/l). In depolarized myocardium (rabbit SA- and AV-node, guinea-pig papillary muscle depolarized by (K+)0 = 27 mmol/l) diltiazem greater than or equal to 0.3 mumol/l reduces amplitude and maximum upstroke velocity of the calcium-dependent action potentials. The decrease in maximum upstroke velocity of the slow response in depolarized guinea-pig papillary muscle is enhanced by elevation of the stimulation frequency, as are the negative inotropic effects (use-dependence). In contrast to nifedipine diltiazem also delays the recovery of the maximum upstroke velocity of the slow response after stimulus-induced inactivation. The reduction of maximum upstroke velocity induced by nifedipine is independent of the rate of activation whereas the blockade induced by diltiazem consists of a small blockade during rest and a profound use-dependent blockade.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002415:Cats; D004110:Diltiazem / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects*; D009928:Organ Specificity; D011188:Potassium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D001552:Benzazepines; D013779:Tetrodotoxin; D004110:Diltiazem; D011188:Potassium