Anticholinergic action of quinidine sulfate in the rabbit atrioventricular node

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.