Muscarinic receptors mediate enhancement of spontaneous GABA release in the chick brain

The functional role of muscarinic acetylcholine receptors in the lateral sp iriform nucleus was studied in chick brain slices. Whole-cell patch-clamp r ecordings of neurons in the lateral spiriform nucleus revealed that carbach ol enhanced GABAergic spontaneous inhibitory postsynaptic currents. The dur ation of the response to carbachol was significantly reduced after blockade of muscarinic receptors with atropine. In the presence of the nicotinic re ceptor antagonist dihydro-beta-erythroidine, carbachol produced a delayed b ut prolonged enhancement of spontaneous GABAergic inhibitory postsynaptic c urrents that was completely blocked by atropine. Muscarine also enhanced th e frequency of spontaneous GABAergic inhibitory postsynaptic currents in a dose-dependent manner, but had no effect on inhibitory postsynaptic current amplitude. While 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochlor ide, a M-3 antagonist, completely blocked muscarine's effect, telenzepine, a M-1 antagonist, and tropicamide, a M-4 antagonist, only partially decreas ed the response to muscarine. Pirenzepine, a M-1 antagonist, and methoctram ine, a M-2 antagonist, potentiated muscarine's enhancement of spontaneous G ABAergic inhibitory postsynaptic currents. Muscarine's action was blocked b y tetrodotoxin, cadmium chloride and omega-conotoxin GVIA, but was not affe cted by dihydro-beta-erythroidine, 6-cyano-7-nitroquinoxaline-2.3-dione, D( -)-2-amino-5-phosphonopentanoic acid, naloxone or fluphenazine. These results demonstrate that activation of both muscarinic and nicotinic acetylcholine receptors can enhance GABAergic inhibitory postsynaptic curre nts in the lateral spiriform nucleus. The muscarinic response has a slower onset but lasts longer than the nicotinic effect. The M-3 receptor subtype is predominantly involved in enhancing spontaneous GABAergic inhibitory pos tsynaptic currents. These M-3 receptors must be located some distance from GABA release sites, since activation of voltage-dependent sodium channels, and consequent activation of N-type voltage-dependent calcium channels, is required to trigger enhanced GABA release following activation of muscarini c receptors. (C) 1999 IBRO. Published by Elsevier Science Ltd.