Abstract
ω-Conotoxin GVIA (ω-conotoxin) is an inhibitor of neuronal voltage sensitive calcium channels (VSCCs). We have examined the effects of various manipulations aimed at elucidating the effects of ω-conotoxin particularly on K + stimulated 45Ca 2+ influx and endogenous acetylcholine (ACh) release. The initial phase of K + stimulated 45Ca 2+ influx was accompanied by a large rapid release of ACh measured by a modification of the chemiluminescent technique of Israël and Lesbats ( J. Neurochem. 39, 248–250, 1982). ACh release was greatly reduced ( ⋍90%) in Ca 2+ free solution or by Cd 2+ (100 μM) period ω-conotoxin (1 μM) completely blocked the initial phase of 45Ca 2+ influx (1–3 s) from synaptosomes and reduced K + stimulated ACh release from tissue slices. ω-Conotoxin (0.1 μM) reduced ACh release which was reversed in the presence of high Ca 2+ concentrations. The dihydropyridine VSCC inhibitor (−)202–791 or agonist (+)202–791 had no effect on ACh release or 45Ca 2+ influx. The pattern of responses on 45Ca 2+ influx and endogenous ACh release was consistent with the suggestion that ω-conotoxin inhibits N-type VSCCs and that these channels are intimately related to ACh release.
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