Adaptation is a process by which hair cells extend their dynamic range, reducing saturation and preventing damage. A tonographic distribution in the adaptation rate of the mechano-electric transducer (MET) current has demonstrate in hair cells of the turtle auditory papilla leading to the suggestions that the rate of adaptation serves as a high pass filter to mechanical stimulation. The purpose of this proposal is to substantiate the filtering properties of adaptation and to elucidate the underling mechanisms involved in establishing this gradient. The possible mechanisms to be addressed include: (i) a distribution in the effective calcium buffering in the stereocilia of hair bundles along the papilla, (ii) a change in the Ca/2+ load per stereocilium, either by varying the number of MET channels per stereocilium or by a variation in the relative calcium permeability of the MET channel across the papilla, (ii) a change in the Ca2+ load per stereocilium, either by varying the number of MET channel across the papilla and, (iii) a change in the relative force exerted by the adaptation processes across the papilla. These possible mechanisms will be addressed by recording the MET currents from hair cells in a newly developed Intact turtle auditory papilla preparation using both whole cell and perforated patch techniques (i-iv). Both displacement-clamp and force-clamp stimuli will be employed. Single-channel measurements, calcium imaging experiments and flash photolysis experiments will be incorporated to better resolve the mechanisms involved in the regulation of calcium homeostasis and the adaptation process. Recently cyclic nucleotides have been reported to shift the set point of the displacement sensitivity of the hair bundle by some unknown mechanism. A fourth topic of study for this proposal will be to characterize the cyclic nucleotide effects and to determine the mechanisms of action. Understanding calcium dynamics in the hair bundle as well as the cyclic nucleotide effects on adaptation have broad implications into the physiologic function of auditory and vestibular hair cells and may underlie the large frequency range at which hair cells are capable of responding. Pathophysiologic implications of alterations in calcium homeostasis in the stereociliary bundle may be linked to both temporary and permanent threshold shifts and noise induced hearing loss.
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