Cholinergic and purinergic neurohumoral signalling in the inner ear: a molecular physiological analysis

The ability to identify the expression of the protein subunits which assemble to form ionotropic receptors for acetylcholine and extracellular adenosine 5'-triphosphate (ATP) in individual cells of the inner ear provides examples of the high resolution and exquisite sensitivity which molecular biology brings to the study of hearing and balance. The data from these studies provide both fine detail with respect to the classification of the elements involved and an overview of the sites of potential interaction of both extracellular and intracellular signalling pathways. The high sensitivity necessitates a molecular physiological approach when using these techniques so that these data on the site and extent of expression can be balanced against functional significance. With the demonstration of expression of the alpha 9 subunit of the nicotinic acetylcholine receptor in cochlear outer hair cells, molecular biology has provided an explanation for the unusual cholinergic receptor pharmacology of the olivocochlear efferent innervation which has confounded investigators for decades. In addition, a role for extracellular ATP as a signalling molecule regulating electrochemical gradients and neurotransmission within the inner ear is supported by the extent of P2 receptor expression in this tissue, data which beg for intense functional study.