Succinylcholine-induced acceleration and suppression of electrically evoked acetylcholine release from mouse phrenic...

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 microM) enhanced evoked [3H]-ACh release, which tended to follow the increase in peak amplitude of tetanic tension; whereas at high concentrations (10 and 30 microM), it simultaneously reduced both release and tension. Decamethonium even at 10 and 30 microM had little effect on [3H]-ACh release despite producing a significantly greater reduction in tension compared with succinylcholine. (+)-Tubocurarine (5 microM) prevented the enhancing effect of [3H]-ACh release induced by 1 microM, but not the decreasing effect induced by 10 microM 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.