Action potential, membrane currents and force of contraction in mammalian heart muscle fibers treated with quinidine.
The effects of quinidine on electrical and mechanical activity were investigated in atrial and/or ventricular heart muscle preparations from guinea pigs and cats. Quinidine (1--100 micrometer) exerted negative inotropic effects in papillary muscles from guinea pigs and cats. In guinea-pig left atria, a positive inotropic effect was superimposed on the negative inotropic effect in response to quinidine. Quinidine (100 micrometer) prolonged the duration of the action potential in guinea-pig atria but shortened it in guinea-pig ventricular muscle. In cat papillary muscles, the late repolarization was markedly prolonged by quinidine, but virtually no change of the plateau phase was observed. The maximal rate of rise and the resting potential were reduced by quinidine in all preparations. Voltage clamp experiments in cat ventricular muscle revealed that the calcium-dependent slow inward current and the outward current of potassium were decreased by quinidine. The effects of quinidine on slow inward current and force of contraction in ventricular muscle were antagonized by isoprenaline (1 micrometer). The results show that the effects of quinidine and the different changes of the action potential configuration can be explained by an unspecific inhibition of the currents of sodium, calcium and potassium. The negative inotropic effect of quinidine is probably related to the depressing effect of the drug on the calcium-dependent slow inward current. The positive inotropic effect of the drug in atrial heart muscle could be related to the prolongation of the action potential which may indirectly improve the influx of calcium during excitation.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002415:Cats; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011802:Quinidine / Q000494:pharmacology*
D011802:Quinidine; D007545:Isoproterenol