Although non-sensory cells constitute most of the tissue lining the cochlear duct, almost nothing is known about their function in the inner ear. With respect to morphology and chemical constituents, the non-sensory cells differ in many ways from the hair cells that transduce sound stimuli and from the auditory nerve cells that transmit auditory information to the brain. Similarities of cochlear non-sensory cells to glia in the central nervous system suggest that, like glia, non-sensory cells may be involved in regulating the ionic composition of extracellular fluids, particularly during periods of high-level sound stimulation. In the past funding period, we discovered that most non-sensory cells lining the cochlear duct belong to one of two gap-junctional networks: an epithelial network in the organ of Corti, and a connective tissue network in the accessory structures. Anatomical features, and the presence at key sites of a variety of proteins known to be important in ion regulation, strongly suggest that these gap junctional networks play important roles in ion homeostasis of cochlear fluids. Furthermore, the presence of proteins within these networks that have been shown to regulate the expression and permeability of gap junctions in other organ system suggest that gap junctions within the cochlea are under dynamic control. In the proposed work we will determine, in non-sensory cells of both gap junctional networks, the resting membrane potentials and the electrophysiological responses to sound stimuli. These measure will indicate whether these networks play roles in the return of potassium ions from the region of hair cells back to the stria vasularis. Using a dye-spread assay, we will test hypotheses concerning dynamic control of cochlear gap junctions by perturbing the system with low-level sound, traumatizing sound, and infusion of chemical agents. In addition, we will examine the effects of acoustic injury on levels of some constituents of the non-sensory cells that are related to ion regulation in the cochlea or elsewhere in the body. The proposed experiments will provide considerable new information about the functional organization in a virtually unexplored aspect of cochlear physiology. Determining the roles that non-sensory cells play in cochlear ion flows will open new areas of investigation into normal cochlear function as well as into mechanisms underlying a variety of otophathologies, especially those involving disorders of fluid homeostasis such as Meniere~s disease.
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