Omega-conotoxin differentially blocks acetylcholine and adenosine triphosphate releases from Torpedo synaptosomes

Abstract

We have examined the effect of several blockers of voltage-sensitive calcium channels on the release of acetylcholine and ATP from synaptosomes isolated from Torpedo marmorata electric organ. Depolarization of these nerve terminals with high K + -containing solutions resulted in a calcium-dependent release of both molecules. Cadmium ions (10 −6 to 10 −3 M) inhibited similarly both releases whereas nickel ions (10 −4 M) in the external medium did not affect either neurotransmitter or nucleotide release. Both releases were completely resistant to the effect of 1,4-dihydropyridines (antagonists nimodipine, nifedipine and agonist Bay K 8644) and of a related compound (diltiazem) at concentrations up to 10 −5 M. These drugs failed to cause any effect even when synaptosomes were submaximally depolarized during incubation. Omega-conotoxin (10 −8 to5 × 10 −5 M) showed a differential effect on acetylcholine and ATP releases. Nucleotide release was inhibited 90% ai the highest concentration tested (50 μm) while acetylcholine release was only moderately decreased (30%). ec 50 values for acetylcholine and ATP were of 167 and 2 μM respectively. The results suggest the implication of different types of calcium channels in the release of these molecules.