Muscarinic receptors modulate the afterhyperpolarizing potential in neostriatal neurons

The actions of carbachol were studied on the firing response of neostriatal neurons recorded intracellularly from in vitro slice preparations of the rat brain. Carbachol (1-10 microM) reversibly reduced the afterhyperpolarization in neostriatal neurons. This effect was accompanied by an increase in both firing frequency and input resistance in the subthreshold voltage range. Atropine (1-10 microM) reversibly blocked carbachol effects, suggesting muscarinic receptor modulation. Pirenzepine (up to 1 microM), but not AF-DX 384 (10 microM) or gallamine (30 microM), blocked the effects of carbachol on the afterhyperpolarization. The protein kinase C activator, phorbol 12,13 dibutyrate, but not the inactive phorbol ester, 4 alpha-phorbol 12-myristate 13-acetate, mimicked carbachol effects. The results suggest that muscarinic receptors, probably of the M1 type, regulate neostriatal excitability by modulating afterhyperpolarization.