Inhibition of neuromuscular transmission in the myenteric plexus of guinea-pig ileum by omega-conotoxins GVIA, MVIIA, MVIIC and SVIB.

1. The effects of a number of Ca2+ channel blockers on the transmural electrical stimulation or receptor agonist-elicited contractile responses of guinea-pig ileum were compared. 2. omega-Conotoxins (MVIIA, GVIA, SVIB and MVIIC), but not omega-agatoxin IVA, completely blocked the twitch responses evoked by low frequency (0.1 Hz) transmural stimulation without inhibition of the contractures evoked by exogenous acetylcholine. The concentration-inhibition curves were shifted by changes of external Ca2+. 3. The tetanic contractures produced by a high frequency (30 Hz) train of stimulation were inhibited by omega-conotoxins by only 25-30%, except for omega-conotoxin MVIIC, which produced about 55% inhibition, all significantly less than that produced by atropine (about 70%) or tetrodotoxin (about 85%). Combinations of omega-conotoxins did not produce additive inhibitory effects. 4. The four omega-conotoxins as well as atropine produced similar partial inhibition (53-62%) of the contractures evoked by dimethylphenylpiperazinium, while tetrodotoxin inhibited the contracture completely. 5. Nifedipine and Ni2+ depressed the nerve stimulation-evoked twitch response and tetanic contracture as well as acetylcholine contracture. 6. These observations suggest that, in the myenteric plexus, a subset of N-type Ca2+ channel dominates under low frequency stimulation, while high frequency stimulation may recruit additional channels and non-cholinergic pathways.