OBSERVATIONS ON THE ROLE OF CALCIUM IONS IN GANGLIONIC RESPONSES TO ACETYLCHOLINE

¹ Department of Pharmacology, School of Medicine. University of Pennsylvania, Philadelphia, Pennsylvania

An electrophysiologic study was made of sympathetic ganglia perfused with Locke solutions of varied electrolyte composition. Ganglionic responses to injected acetylcholine (ACh) and stimulation of the preganglionic nerve during perfusion with Locke solution were comparable to those of a ganglion receiving its normal blood supply. Reduction of the sodium concentration in the perfused medium to 25% of normal produced no significant alterations in the responses of the ganglion to injected ACh and preganglionic nerve stimulation. Lowering the sodium concentration to 12.5% of normal (20 mM) or less revealed the presence of an ACh- induced ganghonic depolarization which was supported by calcium ions. Ganglionic transmission and ACh-evoked postganglionic discharges were completely abolished in these sodium-deficient media. The calcium-dependent, ACh-evoked depolarizations of the ganglion were antagonized by hexamethonium and d-tubocurarine. Interestingly, in the presence of a 12.5% sodium concentration, only a slow negative wave (synaptic potential) was produced by stimulation of the preganglionic nerve at a time when transmission was completely blocked. The synaptic potential was antagonized by hexamethonium and by alterations of the calcium concentration from normal (2.2 mM). Replacement of NaCl by isosmotic CaCl₂ showed that calcium ions can temporarily substitute for sodium ions in maintaining ACh-induced depolarizations of the ganglion. Ganglionic transmission and the postganglionic discharges produced by ACh and KCl were completely abolished at a time when elevated calcium had enhanced the depolarization induced by ACh. The ability of elevated calcium to enhance the ganglionic depolarizations produced by ACh was short-lived (about 15 min). The ganglionic depolarizations evoked by KCl were always depressed in elevated calcium media, thus indicating some specificity of excess alcitum ions for participation in ACh- induced depolarizations. A probable mechanism by which calcium ions can support ACh- induced ganghonic depolarization in solutions extremely deficient in sodium ions is by means of an inward movement of the divalent cation into the ganglion cells under the influence of ACh. It is also possible that sodium ions can compete with calcium ions for entry into the ganglion cells during the action of ACh.