Pharmacological characterization of the calcium-insensitive, intermittent acetylcholine release at the rat...

A variety of pharmacologically active compounds was surveyed for effects on the Ca2+-insensitive miniature end-plate potentials (slow mepps) induced by botulinum toxin type A (Botx) poisoning in rat muscle. The purpose was to gain insight into the release process responsible for this type of acetylcholine secretion. It was found that caffeine and dibutyryl cyclic adenosine 3',5'-monophosphate increased significantly the frequency of slow mepps in Botx-poisoned muscles, but had no effect on slow mepps in control muscles. Vinblastine and cytochalasin B significantly increased the slow mepp frequency in Botx-poisoned as well as in normal control muscles. Inhibitors of oxidative metabolism reduced the frequency of slow mepps by 90%, indicating a high energy requirement for this type of release. No agent was found to augment the slow mepp frequency above 1-2 Hz, suggesting that an upper limit exists for this type of packaging and release of acetylcholine.