Distinct muscarinic receptors enhance spontaneous GABA release and inhibitelectrically evoked GABAergic synaptic transmission in the chick lateral spiriform nucleus

The effects of muscarinic agonists on GABAergic synaptic transmission were examined using whole-cell patch-clamp recording in chick brain slices conta ining the lateral spiriform nucleus. Bath application of muscarine (10 muM) both increased the frequency of spontaneous GABAergic postsynaptic current s and reduced the amplitude of evoked GABAergic polysynaptic postsynaptic c urrents elicited by focal afferent fiber electrical stimulation. Both of th ese muscarinic actions were reversible and dose-dependent. Two M-1 antagoni sts. telenzepine and pirenzipine, and to a lesser extent the M-2 antagonist methoctramine, protected against muscarine's inhibition of the evoked poly synaptic currents. Other M-2 antagonists (tripitramine and gallamine) as we ll as the M-3 antagonist 4-DAMP mustard (4-diphenylacetoxy-N-(2-chloroethyl )- piperidine hydrochloride) and an M-4 antagonist (tropicamide) provided l ittle or no protection against muscarine in this assay. In contrast, 4-diph enylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride. tropicamide and tel enzepine, but not pirenzepine. methoctramine, tripitramine and gallamine, b locked muscarine's enhancement of spontaneous GABAergic currents. McN-A-343 [(4-hydroxy-2-butynyl)-1-trimethylammonium-m-chlorocarbanilate chloride] a nd CDD-0097 (5-propargyloxycarbonyl-1,4,5,6-tetrahydropyrimidine hydrochlor ide), two M-1 agonists, mimicked muscarine's inhibition of the evoked polys ynaptic GABAergic currents but did not mimic muscarine's enhancement of spo ntaneous GABAergic currents, Both actions of muscarine persisted when slice s were pretreated with pertussis toxin or N-ethylmaleimide. which inactivat e G-proteins coupled to M-2 and M-4 receptors while leaving G-proteins coup led to M-1, M-3 and M-5 receptors intact. Muscarine had no significant effe ct on the amplitude of the direct postsynaptic current elicited by exogenou s GABA in the presence of tetrodotoxin. The results demonstrate that distinct muscarinic receptors oppositely modul ate GABAergic transmission in the lateral spiriform nucleus, The receptor m ediating the inhibition of evoked GABAergic polysynaptic currents is pharma cologically similar to an M-1 receptor, while the enhancement of spontaneou s GABAergic currents appears to be mediated by an M-3 receptor. (C) 2001 IB RO. Published by Elsevier Science Ltd. All rights reserved.