P-type Ca2+ channels trigger stimulus-evoked [3H]acetylcholine release from mammalian motor endplates

In the present experiments it was tested whether omega-agatoxin-IVA, a peptide blocking P-type voltage-dependent Ca2+ channels, inhibits the evoked release of newly synthesized [3H]acetylcholine from the rat phrenic nerve. Release of [3H]acetylcholine was evoked by electrical stimulation of the isolated phrenic nerve (100 or 750 pulses at 5 Hz). omega-Agatoxin-IVA inhibited evoked [3H]acetylcholine release in a concentration-related manner; inhibition started at a concentration of 30 nM with complete block occurring at 500 nM. In conclusion, the present experiments demonstrate that omega-agatoxin-IVA-sensitive P-type Ca2+ channels are critically involved in the regulation of stimulus-induced transmitter release at mammalian motor endplates.