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.
Smith
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Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Australia.
Cunnane
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D010455:Peptides; D010456:Peptides, Cyclic; D011978:Receptors, Nicotinic; D020960:omega-Conotoxins; C082807:omega-grammotoxin SIA; D002104:Cadmium; C075851:omega-conotoxin-MVIIC; D018738:Hexamethonium; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D000109:Acetylcholine