Muscarinic receptor subtypes in rat dorsal cochlear nucleus

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 M1-M4 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 (IC50) of regular and bursting neurons were estimated for each antagonist. Correlation coefficients were calculated between log(IC50) values and log(Ki) values of the drugs for the receptor subtypes. Correlation coefficients for both regular and bursting neurons were not significant (P > 0.05) for M1 and M3, but were significant (P < 0.02) for M4. Bursting but not regular neurons also showed a significant correlation for M2 (P < 0.05). Our results suggest that (1) M4 contributes to the cholinergic responses in DCN and M2 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.