N- and P-type Ca2+ channels are involved in acetylcholine release at a neuroneuronal synapse: only the N-type channel is the target of neuromodulators.
Cholinergic transmission in an identified neuro-neuronal synapse of the Aplysia buccal ganglion was depressed by application of a partially purified extract of the funnel-web-spider venom (FTx) or of its synthetic analog (sFTx). This specific blocker of voltage-dependent P-type Ca2+ channels did not interfere with the effect of the N-type Ca2+ channel blocker omega-conotoxin, which could further decrease synaptic transmission after a previous application of FTx. Similar results were obtained when the reversal order of application of these two Ca2+ channel blockers was used. Both P- and N-type Ca2+ currents trigger acetylcholine release in the presynaptic neuron. The neuromodulatory effects of FMRF-amide, histamine, and buccalin on transmitter release disappeared after the blockade of the N-type Ca2+ channels but remained still effective in the presence of FTx. These results indicate that only N-type Ca2+ channels appear to be sensitive to the neuromodulators we have identified.
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Laboratoire de Neurobiologie Cellulaire et Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
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D000109:Acetylcholine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004553:Electric Conductivity; D017952:Ganglia, Invertebrate / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018377:Neurotransmitter Agents; D013111:Spider Venoms; D000109:Acetylcholine