LOCALIZATION OF FUNCTIONAL MUSCARINIC RECEPTORS IN THE RAT COCHLEA - EVIDENCE FOR EFFERENT PRESYNAPTIC AUTORECEPTORS

In the rat cochlea, the activation of muscarinic receptors stimulates the hydrolysis of phosphoinositides but the importance of this muscari nic effect is still unknown. In order to find out about the role of th e muscarinic receptors in the cochlea, we examined their functional di stribution within this organ. This was achieved by measuring the forma tion of [H-3]inositol phosphates induced by carbachol (1 mM) in two re gions of the cochlea: the modiolus and the organ of Corti. At both sit es, carbachol enhanced the accumulation of inositol phosphates in an a tropine-sensitive way. These stimulations were completely antagonised by 4-diphenylacetoxy-N-methyl piperidine methiodide (1 muM) but unchan ged by pirenzepine (1 muM). In cochleas depleted of outer hair cells b y a treatment with amikacin, the carbachol-induced formation of inosit ol phosphates is not altered with respect to control, undamaged cochle as. Conversely, when the medial cholinergic axons which form synapses with the outer hair cells are destroyed by the section of the crossed olivocochlear bundle the carbachol-stimulated inositol phosphates resp onse is reduced by 35% in the organ of Corti. This section has no effe ct in the modiolus, despite the degeneration of some modiolar fibers. Our results show that functional muscarinic receptors are distributed both in the organ of Corti and in the modiolus. These two structures c ontain presumably the same class of cholinoceptor. The effects of sele ctive destruction clearly demonstrate that a population of muscarinic receptors is located on presynaptic membranes at the level of the medi al axon-outer hair cell contacts. They also point to spiral ganglion n eurons and/or the Schwann cells as sites for the functional cholinocep tors in the modiolus.