Muscarinic receptor subtypes in rat dorsal cochlear nucleus

Abstract

We previously reported that responses of spontaneously active rat dorsal cochlear nucleus (DCN) neurons to cholinergic agonists are mediated predominantly by muscarinic receptors. We have now tested the effects of 7 antagonists with differing affinities for the muscarinic receptor subtypes M 1–M 4 on the responses to constant, submaximal doses of carbachol in rat brainstem slices. Each slice was exposed to one or more concentrations of one antagonist applied during extracellular recording of a DCN neuron. The concentrations yielding 50% reduction of test responses (IC 50) of regular and bursting neurons were estimated for each antagonist. Correlation coefficients were calculated between log(IC 50) values and log( K i) values of the drugs for the receptor subtypes. Correlation coeffi for both regular and bursting neurons were not significant ( P>0.05) for M 1 and M 3, but were significant ( P<0.02) for M 4. Bursting but not regular neurons also showed a significant correlation for M 2 ( P<0.05). Our results suggest that (1) M 4 contributes to the cholinergic responses in DCN and M 2 may also contribute to the responses of bursting neurons, but the contribution of other subtypes cannot be completely excluded; (2) muscarinic subtypes in DCN probably differ from those reported for cochlea and some brain regions.