N-TYPE AND P-TYPE CA2-RELEASE AT A NEURONEURONAL SYNAPSE - ONLY THE N-TYPE CHANNEL IS THE TARGET OF NEUROMODULATORS( CHANNELS ARE INVOLVED IN ACETYLCHOLINE)

Cholinergic transmission in an identified neuro-neuronal synapse of th e Aplysia buccal ganglion was depressed by application of a partially purified extract of the funnel-web-spider venom (FTx) or of its synthe tic analog (sFTx). This specific blocker of voltage-dependent P-type C a2+ channels did not interfere with the effect of the N-type Ca2+ chan nel blocker omega-conotoxin, which could further decrease synaptic tra nsmission after a previous application of FTx. Similar results were ob tained when the reversal order of application of these two Ca2+ channe l blockers was used. Both P- and N-type Ca2+ currents trigger acetylch oline release in the presynaptic neuron. The neuromodulatory effects o f FMRF-amide, histamine, and buccalin on transmitter release disappear ed after the blockade of the N-type Ca2+ channels but remained still e ffective in the presence of FTx. These results indicate that only N-ty pe Ca2+ channels appear to be sensitive to the neuromodulators we have identified.