The long-term goal of this project is to show how head movement stimuli are processed by the sensory cells (hair cells) of the mammalian utricle, a vestibular organ of the inner ear. The majority of vestibular disorders, which may lead to debilitating disequilibrium, result from pathology of the vestibular organ and dysfunction of the hair cells. The proposed research will investigate normal mechanisms of stimulus processing by hair cells of the rodent utricle. These mechanisms include 1) transduction by hair cells of mechanical stimuli into an ionic current (the transduction current) and 2) voltage-dependent processing; ionic currents through voltage-dependent channels that are modulated by the voltage change evoked by the transduction current. The transduction and voltage-dependent currents of single hair cells, and a new preparation, utricles cultured from mice in the first week after birth. Preliminary results from both preparations suggest that the voltage-dependent currents of two types of hair cells (type I and II) differ sufficiently to cause substantial differences in stimulus processing. Experiments proposed here will follow up on these observations by thoroughly characterizing the voltage-dependent currents and their effects on the hair cells' voltage response. Mature hair cells can be studied with the isolated cell preparation. The cultures, while restricted to the first postnatal week, offer the advantage that the hair cells have not been subject to enzymatic dissociation procedures. The cultures are also superior for experiments on transduction, which will measure individual hair cells' transduction currents in response to a moving probe, and for investigating how transduction and voltage-dependent currents vary with region in the utricular epithelium. These electrophysiological studies will be complemented by electron microscopic studies of the anatomy of cultured and acutely excise utricles. In addition to answering questions of basic sensory processing, the proposed experiments would establish the cultured utricles as a model preparation in which to examine vestibular organ function in normal and pathological conditions.
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