Baux_1993_Neurosci_53_581

Changes in evoked acetylcholine quantal release induced by histamine, FLRFamide and buccalin were investigated at an identified neuro-neuronal synapse in the buccal ganglion of Aplysia californica. Regulation of acetylcholine release by these neuromodulators was correlated with their actions on the presynaptic Ca2+ current. We have previously reported that FLRFamide and histamine, respectively, increase and decrease acetylcholine release from buccal neurons B4/B5. Buccalin, a peptide specific to the buccal ganglion, lowered the number of acetylcholine quanta released. Consistent with the synaptic effects, the presynaptic nifedipine-resistant Ca2+ current that triggers the release of acetylcholine in B4/B5 neurons [Trudeau L.-E. et al. (1993) Neuroscience 53, 571-580] was lowered by buccalin or by histamine and enhanced by FLRFamide. The analysis of tail currents showed that histamine shifts the voltage dependence of the nifedipine-resistant Ca2+ channels towards more positive voltages, whereas FLRFamide has an opposite action. Buccalin did not affect the voltage dependence of the channels but depressed the amplitude of the Ca2+ current, an effect which could be due either to a reduction of the number of available Ca2+ channels, to a decrease of their unitary conductance or to a modification of their gating. Inactivation of presynaptic G proteins prevented the modulatory actions of FLRFamide and histamine on quantal acetylcholine release and also on the voltage dependence of the nifedipine-resistant Ca2+ channels. This procedure, however, failed to prevent the suppressive effects of buccalin. The possibility of relating the voltage dependence shifts of the Ca2+ current induced by FLRFamide and histamine to the phosphorylation state of the Ca2+ channels is discussed. It is concluded that three independent presynaptic pathways initiated by histamine, FLRFamide and buccalin control presynaptic Ca2+ influx, these modulations being apparent within the physiological range of voltages required to activate Ca2+ channels.