Inhibitory effect of ionized free intracellular calcium enhanced by ruthenium red and m-chloro-carbonylcyanide phenyl hydrazon on the evoked release of acetylcholine

In order to understand the relationship between the free ionized calcium concentration in the axon terminals and the transmitter release we have investigated the effect of ruthenium red (RuR) and m-chloro-carbonylcyanide phenyl hydrazon (CCCP), mitochondrial uncoupler agents on the liberation of acetylcholine from myenteric plexus of guinea-pig ileum. Both compounds are able to enhance intracellular free Ca 2+. In the presence of RuR and CCCP the spontaneous release of radioactivity from isolated myentericplexus preparation, previously loaded with (methyl-3 H)-choline chloride was significantly enhanced while that evoked by electrical stimulation was decreased. Atropine did not affect the electrically evoked release in the presence of CCCP, indicating that in the effect of CCCP the presynaptic muscarinic receptors mediated negative feedback modulation does not play any role. Our findings are consistent with the hypothesis that the enhanced level of intracellular free Ca 2+ enhances the spontaneous while depresses the electrically evoked release of transmitter.