Calcium channels controlling acetylcholine release in the guinea-pig isolated anterior pelvic ganglion: an electropharmacological study.

An electropharmacological analysis of the type(s) of calcium channel controlling neurotransmitter release in preganglionic sympathetic nerve terminals in the guinea-pig anterior pelvic ganglion has been carried out. Conventional intracellular recording techniques were used to record excitatory postsynaptic potentials as a measure of neurotransmitter release. Excitatory postsynaptic potentials were abolished by hexamethonium (30-100 microM) and are therefore mediated by acetylcholine acting at nicotinic receptors. In studies of more than 150 cells, the N-type calcium channel blocker omega-conotoxin GVIA (100-300 nM) failed to block the initiation of the nerve impulse by the excitatory postsynaptic potential. In single-cell studies, omega-conotoxin GVIA (1 microM) sometimes altered the configuration of the excitatory postsynaptic potential/cell body nerve action potential complex, but on only one occasion was the excitatory postsynaptic potential reduced below the threshold required to initiate the action potential. Nifedipine (10 microM), omega-agatoxin IVA (100 nM) and omega-conotoxin MVIIC (300 nM), applied alone or in combination with omega-conotoxin GVIA (300 nM), were also ineffective. However, excitatory postsynaptic potentials evoked by trains of stimuli (0.1-0.5 Hz) were markedly reduced or abolished by the non-specific calcium channel blocker omega-grammotoxin SIA (300 nM). When trains of stimuli were delivered at higher frequencies (4 Hz), the block induced by omega-grammotoxin SIA could be overcome, and excitatory postsynaptic potentials were able to initiate action potentials even when omega-conotoxin GVIA, omega-agatoxin IVA and omega-conotoxin MVIIC were also present. The calcium channel(s) controlling acetylcholine release was (were) blocked by low concentrations of cadmium ions (30 microM) at all stimulation frequencies studied (0.1-50 Hz). Thus, the dominant calcium channels controlling acetylcholine release in sympathetic ganglia are not the L, N, P or Q types. At low frequencies of stimulation, omega-grammotoxin SIA-sensitive calcium channels play a dominant role in acetylcholine release, but at higher stimulation frequencies yet another pharmacologically distinct calcium channel (or subtype) supports neurotransmitter release.