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 contro lling neurotransmitter release in preganglionic sympathetic nerve terminals in the guinea-pig anterior pelvic ganglion has been carried out. Conventio nal intracellular recording techniques were used to record excitatory posts ynaptic potentials as a measure of neurotransmitter release. Excitatory pos tsynaptic potentials were abolished by hexamethonium (30-100 mu M) and are therefore mediated by acetylcholine acting at nicotinic receptors. In studi es of more than 150 cells, the N-type calcium channel blocker omega-conotox in GVIA (100-300 nM) failed to block the initiation of the nerve impulse by the excitatory postsynaptic potential. In single-cell studies, omega-conot oxin GVIA (1 mu M) sometimes altered the configuration of the excitatory po stsynaptic potential/cell body nerve action potential complex, but on only one occasion was the excitatory postsynaptic potential reduced below the th reshold required to initiate the action potential. Nifedipine (10 mu M), om ega-agatoxin IVA (100 nM) and omega-conotoxin MVIIC (300 nM), applied alone or in combination with omega-conotoxin GVIA (300 nM), were also ineffectiv e. 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 wer e delivered at higher frequencies (4 Hz), the block induced by w-grammotoxi n SIA could be overcome, and excitatory postsynaptic potentials were able t o initiate action potentials even when w-conotoxin GVIA, w-agatoxin IVA and omega-conotoxin MVIIC were also present. The calcium channel(s) controllin g acetylcholine release was (were) blocked by low concentrations of cadmium ions (30 mu M) at all stimulation frequencies studied (0.1-50 Hz). Thus, t he dominant calcium channels controlling acetylcholine release in sympathet ic,ganglia are not the L, N, P or Q types. At low frequencies of stimulatio n, w-grammotoxin SIA-sensitive calcium channels play a dominant role in ace tylcholine release, but at higher stimulation frequencies yet another pharm acologically distinct calcium channel (or subtype) supports neurotransmitte r release. (C) 1999 EBRO. Published by Elsevier Science Ltd.