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

The functional role of muscarinic acetylcholine receptors in the lateral spiriform nucleus was studied in chick brain slices. Whole-cell patch-clamp recordings of neurons in the lateral spiriform nucleus revealed that carbachol enhanced GABAergic spontaneous inhibitory postsynaptic currents. The duration of the response to carbachol was significantly reduced after blockade of muscarinic receptors with atropine. In the presence of the nicotinic receptor antagonist dihydro-β-erythroidine, carbachol produced a delayed but prolonged enhancement of spontaneous GABAergic inhibitory postsynaptic currents that was completely blocked by atropine. Muscarine also enhanced the 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 hydrochloride, a M 3 antagonist, completely blocked muscarine's effect, telenzepine, a M 1 antagonist, and tropicamide, a M 4 antagonist, only partially decreased the response to muscarine. Pirenzepine, a M 1 antagonist, and methoctramine, a M 2 antagonist, potentiated muscarine's enhancement of spontaneous GABAergic inhibitory postsynaptic currents. Muscarine's action was blocked by tetrodotoxin, cadmium chloride and ω-conotoxin GVIA, but was not affected by dihydro-β-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 currents 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 postsynaptic 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 muscarinic receptors.