The effects of the dihydropyridine (DHP) Ca2+ channel antagonist, nifedipine, were studied on the cholinergic synapse between the presynaptic neurones B4/B5 and the postsynaptic neurones B3/B6 located in the buccal ganglion of Aplysia californica. Nifedipine (10 microM) decreased the presynaptic Ca2+ current by 30%-40%. Blockade of DHP-sensitive Ca2+ channels, however, did not affect quantal transmitter release from the presynaptic neurones. Thus, at this synapse, DHP-sensitive Ca2+ channels appear not to be involved in acetylcholine (ACh) release. The postsynaptic response to an ionophoretic application of ACh was decreased by nifedipine, pointing to a blocking action of the drug on the postsynaptic receptor/channel complex. Nifedipine was also found to activate protein kinase C, which in turn induces an increase in the nifedipine-resistant presynaptic Ca2+ influx and in the number of released ACh quanta. These effects of nifedipine could be prevented by a previous application of 1,5-(isoquinolinylsulfonyl)-2-methyl-piperazine (H-7), a protein kinase blocker.