Meniere's Disease is one of the pathological entities characterized by endolymphatic hydrops of the cochlear and vestibular labyrinths. Hydrops can result from an alteration of ion transport properties of the epithelial cells bordering the endolymphatic system. Little is known about the cellular basis of the pathologic processes involved because data are lacking from normal as well as pathological systems concerning active and passive mechanisms of secretion and absorption of ions. Endolymph is unique in that it is the only extracellular fluid in the body with a high potassium (K+) concentration and low sodium (Na+) and calcium (Ca2+) concentrations. It is proposed to study the ion transport processes responsible for fluxes of K+, Na+ and Ca2+ in the vestibular labyrinth and cochlea, specifically vestibular dark cells (VDC) and strial marginal cells (SMC), by further utilization of electrophysiologic techniques and in vitro preparations developed in this laboratory. Specific issues to be addressed by the proposed studies include a) whether the specific membrane conductances present in basal and intermediate cells of the stria vascularis can provide the basis for generation of the large endocochlear potential; b) whether the K+ flux across the apical membrane of VDC and SMC is entirely electrogenic or whether electroneutral K+ flux contributes to secretion or reabsorption of K+ under unstimulated conditions and during activation of intracellular regulatory pathways; c) determination of the constituents of two biochemical regulatory pathways purported to control K+ secretion by VDC and SMC, the cyclic AMP pathway and an autocrine purinergic receptor pathway, and their effectors in these cells; d) whether VDC and SMC support transepithelial Na+ and/or Ca2+ fluxes. Specific parameters to be measured include transepithelial voltage and resistance with the micro-Ussing chamber, transepithelial fluxes of K+, Na+ and Ca2+ with the ion-selective vibrating probe, and electrical properties of cell membranes with several configurations of the patch clamp technique, including on-cell macro patch. The vibrating probe and macro patch clamp techniques are the most powerful methods for addressing the questions posed in this application and this laboratory is the only one in the world applying them to the study of inner ear function.
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