Effects of Acetylcholine on Action Potential Characteristics of Atrial and Ventricular Myocardium after Bilateral Cervical Vagotomy in the Cat Richard

Acetylcholine, the parasympathetic neurotransmitter, shortens the action potential duration of cat atrial muscle cells, but not ventricular muscle cells. In mammalian species, atrial tissue receives a richer cholinergic nerve supply than ventricular tissue. To determine whether chronic withdrawal of cholinergic tone might influence the subsequent response of these tissues to cholinergic stimulation, we examined the effect of acetylcholine on the action potentials of atrial and ventricular myocytes from cats with intact vagi and cats after chronic bilateral cervical vagotomy. Following bilateral cervical vagotomy, physostigmine (10~ M) failed to alter atrial tension development or action potential duration. Acetylcholine produced shortening of the action potential duration in atrial muscle from cats with intact vagi and in cats following bilateral cervical vagotomy. However, the degree of shortening produced by acetylcholine after bilateral cervical vagotomy was significantly greater (P < 0.001). In ventricular muscle from cats with intact vagi, acetylcholine did not alter action potential duration. In ventricular muscle from cats after bilateral cervical vagotomy, acetylcholine shortened the action potential duration. Maximal effect was seen at a concentration of 10~ M where acetylcholine shortened action potential duration at 90% repolarization from a control value of 179 ± 4 to 150 ± 7 msec. Atropine (10~ M) reversed the effects of acetylcholine. Addition of propranolol (10~ M) to the superfusate or pretreatment of the animals with reserpine (2 mg/kg, ip) 24 hours before sacrifice failed to alter the response of ventricular muscle cells to acetylcholine. We conclude that after bilateral cervical vagotomy, acetylcholine produces an exaggerated effect on atrial action potential duration, and produces a direct effect on the action potential duration of ventricular myocytes. These effects are mediated through muscarinic cholinergic receptors. (Circ Res 56: 613-620, 1985)