title: Anticholinergic action of quinidine sulfate in the rabbit atrioventricular node.
abstract: Anticholinergic action of quinidine sulfate was electrophysiologically studied by recording spontaneous action potentials and membrane current of the rabbit atrioventricular node. In the presence of 0.1 mumol/l carbachol, the spontaneous activity of the atrioventricular nodal preparations was markedly inhibited, whereas subsequent addition of 1, 5 and 20 mumol/l quinidine restored automaticity in a concentration-dependent manner. In some preparations, quinidine at concentrations of 5 mumol/l and higher slowed the spontaneous activity by its direct membrane action even in the presence of carbachol. The dose-response curve for acetylcholine action on the spontaneous firing frequency showed that one molecule of acetylcholine bound to one muscarinic receptor of the atrioventricular node cell (Hill coefficient = 1.2). A parallel shift of this curve towards higher acetylcholine concentrations was observed at 0.03, 0.1 and 0.3 mumol/l but not at 1 and 3 mumol/l quinidine, suggesting a noncompetitive antagonism of quinidine against acetylcholine. Voltage clamp experiments revealed that 5 mumol/l quinidine reduced the slow inward current, hyperpolarization-activated inward current, and delayed rectifying K+ current, through its membrane actions. Quinidine at this concentration almost completely suppressed the acetylcholine-activated K+ current, which showed a relaxation phenomenon. Hence, the direct blockage of the acetylcholine-activated K+ current by quinidine was considered responsible for the anticholinergic action of this drug. We conclude that quinidine is a non-specific ionic channel blocker that inhibits all the membrane currents in the atrioventricular node including the acetylcholine-activated K+ current.
authors.affiliation: Cardiovascular Institute, Fujita Health University School of Medicine, Aichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: R M
authors.initials: RM
authors.lastname: Huan
authors.forename: Y
authors.initials: Y
authors.lastname: Habuchi
authors.forename: N
authors.initials: N
authors.lastname: Homma
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects*; D001285:Atropine / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010276:Parasympatholytics; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D010276:Parasympatholytics; D015221:Potassium Channels; D001285:Atropine; D011802:Quinidine