Inhibition of acetylcholine release from mouse motor nerve by a P-type calcium channel blocker, omega-agatoxin IVA.

1. The effects were studied of the central neurone P-type Ca2+ channel blockers, omega-agatoxin IVA, omega-conotoxin MVIIC (polypeptide toxins) and synthetic funnel-web spider polyamine toxin on acetylcholine release from mouse motor nerve. 2. omega-Agatoxin IVA decreased the quantal content of endplate potentials and blocked synaptic transmission in the nanomolar range in a reversible manner, whereas the other toxins depressed transmission in the hundred micromolar range. 3. The polyamine toxin, but not the polypeptide toxins, decreased the amplitude of the miniature endplate potential. The increase in the frequency of miniature endplate potentials evoked by high [K+], but not that evoked by alpha-latrotoxin, was effectively antagonized by omega-agatoxin IVA. 4. In the presence of omega-agatoxin IVA, high frequency nerve stimulation produced facilitation of endplate currents and tetanic contractions. 5. The results suggest that, under physiological conditions, the Ca2+ necessary for nerve action potential-evoked acetylcholine release is translocated via a subtype of the P-type Ca2+ channel sensitive to omega-agatoxin IVA.