The cellular electrophysiologic mechanism of the dual actions of disopyramide on rabbit sinus node function.
To determine the contribution of disopyramide's suggested opposing direct depressant and indirect acceleratory actions on sinus node function, we studied the effects of disopyramide, 1 x 10(-7) to 1 x 10(-4) M, on isolated rabbit sinus node preparations using standard microelectrode techniques. Transmembrane potentials were recorded simultaneously from the sinus node and adjoining crista terminalis area. Disopyramide, as much as 1 x 10(-5) M, had no effects on the sinus cycle length. At a concentration of 1 x 10(-4) M, sinus cycle length was significantly prolonged due to prolongation of the sinus nodal action potential duration. During cholinergic blockade with atropine, 1 x 10(-6) M, disopyramide, 1 x 10(-7) to 1 x 10(-4) M, significantly prolonged sinus cycle length as a result of a prolongation of the sinus nodal action potential duration and a decrease of the slope of phase 4 depolarization. During cholinergic stimulation with carbamyl choline, 1 x 10(-9) M, disopyramide, 1 x 10(-7) to 1 x 10(-6) M, tended to reverse carbamyl choline-induced prolongation of the sinus cycle length (NS). This acceleratory action of disopyramide was caused by a significant increase of the slope of phase 4 depolarization. Disopyramide, 1 x 10(-7) to 1 x 10(-4) M, had no significant effects on corrected sinus node recovery time or on sinoatrial conduction time under any conditions studied. We conclude that disopyramide has a direct depressant action on normal sinus node cells at the upper therapeutic and toxic levels, which is enhanced during cholinergic blockade, and that disopyramide's acceleratory action appears only at much lower concentrations and only during cholinergic stimulation.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016275:Atrial Function; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004206:Disopyramide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology*
D011725:Pyridines; D001285:Atropine; D002217:Carbachol; D004206:Disopyramide