Project 12

Regulation of cochlear function by ATP receptors

Hearing sensitivity is determined by a number of variables in the peripheral receptor organ. One of these is the steady voltage in the scala media, the fluid compartment into which the stereocilia of the hair cells project. This voltage is a vital element in the total driving force on ions through the hair cell transduction channels. Disturbances of this voltage could underly a variety of hearing pathologies including tinnitus and hence it is interesting to study the mechanism by which it is regulated. We have consistently found that perfusion of the cochlea with agonists of receptors for ATP (so-called purinergic receptors) causes a marked rise in the voltage in the scala media (endocochlear potential). Three possible hypotheses of the mechanism of this increase are 1) that there is a change in activity in an efferent feedback loop regulating the voltage, 2) that there is activation of P2 receptors in the stria vascularis (the transporting epithelium that is responsible for generating the voltage) and 3) that there is a reduction in the current drain on the scala media voltage by closure of ion channels in hair cells and/or supporting cells lining the scala media. These hypotheses will be tested by a series of experiments using intracochlear perfusion and intracochlear electrical measurements