Succinylcholine-Induced Acceleration and Suppression of Electrically Evoked Acetylcholine Release from Mouse Phrenic Nerve-Hemidiaphragm Muscle Preparation

Abstract

The effects of a depolarizing neuromuscular blocker on electrically evoked acetylcholine (ACh) release were studied using a mouse phrenic nerve-diaphragm muscle preparation preloaded with [³H]-choline, and the changes in muscle tension were recorded simultaneously. Succinylcholine at a low concentration (1 μM) enhanced evoked [³H]-ACh release, which tended to follow the increase in peak amplitude of tetanic tension; whereas at high concentrations (10 and 30 μM), it simultaneously reduced both release and tension. Decamethonium even at 10 and 30 μM had little effect on [³H]-ACh release despite producing a significantly greater reduction in tension compared with succinylcholine. (+)-Tubocurarine (5 μM) prevented the enhancing effect of [³H]-ACh release induced by 1 μM, but not the decreasing effect induced by 10 μM succinylcholine. These results suggest that succinylcholine induced acceleration at low concentrations due to a positive feedback mechanism through presynaptic nicotinic ACh receptors and the inhibition of ACh release at high concentration contributes in part to the neuromuscular blockade.