Abstract

Comparisons were made of the actions on sympathetic ganglia of acetylcholine (ACh) and methacholine (MCh). Unlike ACh, MCh evoked postganglionic firing which was late in onset and was sensitive to blockade by small doses of atropine. Relatively large doses of hexamethonium (C₆) had no effect on the response to MCh. An analysis of the ganglionic potentials evoked by ACh and MCh revealed further differences between the two agents. In both normal and denervated ganglia, ACh evoked ganglionic depolarization which coincided with the postganglionic firing. In many of the experiments the depolarization was followed by hyperpolarization. The ganglionic potentials evoked by MCh consisted of an initial period of hyperpolarization which was followed by depolarization. The depolarization produced by MCh coincided with postganglionic firing. The postganglionic nerve was electrically silent during the hyperpolarization of the ganglia.

The blockade of transmission produced by ACh occurred during both periods of the ganglionic potential. On the other hand, the blockade produced by MCh occurred only during the period of hyperpolarization evoked by this agent.

Treatment of the ganglia with small doses of atropine had no effect on the ganglionic potentials evoked by ACh but blocked completely the potentials produced by MCh. In addition, atropine antagonized the depression of transmission produced by either ACh or MCh.

These findings suggest, (1) that the blockade of ganglionic transmission produced by ACh and MCh occurred by basically different mechanisms, (2) that the activation of an inhibitory mechanism by MCh was the basis of the blockade caused by this agent and (3) that the blockade by ACh of transmission is not related always to ganglionic depolarization.