Localisation of functional muscarinic receptors in the rat cochlea: evidence for efferent presynaptic autoreceptors

Abstract

In the rat cochlea, the activation of muscarinic receptors stimulates the hydrolysis of phosphoinositides but the importance of this muscarinic effect is still unknown. In order to find out about the role of the muscarinic receptors in the cochlea, we examined their functional distribution within this organ. This was achieved by measuring the formation of [3H]inositol phosphates induced by carbachol (1 mM) in two regions of the cochlea: the modiolus and the organ of Corti. At both sites, carbachol enhanced the accumulation of inositol phosphates in an atropine-sensitive way. These stimulations were completely antagonised by 4-diphenylacetoxy-N-methyl piperidine methiodide (1 microM) but unchanged by pirenzepine (1 microM). In cochleas depleted of outer hair cells by a treatment with amikacin, the carbachol-induced formation of inositol phosphates is not altered with respect to control, undamaged cochleas. 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 response is reduced by 35% in the organ of Corti. This section has no effect 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 contain presumably the same class of cholinoceptor. The effects of selective destruction clearly demonstrate that a population of muscarinic receptors is located on presynaptic membranes at the level of the medial axon-outer hair cell contacts. They also point to spiral ganglion neurons and/or the Schwann cells as sites for the functional cholinoceptors in the modiolus.