The generation and maintenance of large ion and voltage gradients between cochlear endolymph and perilymph is essential for normal hearing. Alterations in these gradients underlie the auditory dysfunction in Meniere's disease and certain metabolic and genetic disorders, and account for a large amount of the hearing loss seen with age. The stria vascularis is generally accepted as the main tissue site responsible for generating the cochlea's electrochemical gradients. More recent studies, however, have provided evidence for the active participation of complex networks of supporting cells and fibrocytes in the regulation of inner ear ion and fluid balance, and point to the need for more comprehensive studies of cochlear ion transport mechanisms. The overall goal of this project is to increase understanding of inner ear ion homeostasis in general, and of the specific molecular and cellular mechanisms mediating cochlear K+ flux, in particular. There are three complimentary Specific Aims.
Aim 1 seeks to identify and define the cell-type specific distribution of members of three ion transport protein families suspected to reside in several of the unique cell types thought to be involved with intercellular K+ recycling.
Aim 2 will characterize, in vitro, the membrane conductance and K+ transport properties of several different cell types in the lateral K+ recirculation pathway.
Aim 3 proposes to pharmacologically manipulate various ion transport mediators in the putative recycling pathways in vivo, and to ascertain electrophysiological, as well as potential histochemical and histopathological changes resulting from these perturbations. Data obtained through this comprehensive yet highly focused study will serve to verify and extend current models of inner ear ion homeostasis and provide information of importance in the design of therapies for disorders associated with inner ear electrochemical imbalances.
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