omega-Conotoxin reduces facilitation of transmitter release at the frog neuromuscular junction.

We have examined the effects of the peptide toxin omega-conotoxin GVIA (omega-CgTx), a known calcium channel blocker, on stimulation-induced changes in end-plate potential (EPP) amplitude at the frog neuromuscular junction. We found that the addition of this toxin in submicromolar concentrations reduced both the control EPP amplitude and the increase in EPP amplitude that normally occurs during repetitive stimulation under low quantal conditions. These effects of omega-CgTx developed slowly following its addition to the bathing solution, were concentration-dependent and were essentially irreversible. The effects of omega-CgTx appeared to result from reductions in the facilitation and augmentation components of stimulation-induced increases in release. While the effects of omega-CgTx on EPP amplitude could be reversed by increasing the extracellular concentration of Ca2+, we were unable to reverse the effects of the toxin on stimulation-induced increases in EPP amplitude. Thus it appears that omega-CgTx has a dual effect on neuromuscular transmission, perhaps by acting at two different presynaptic sites.