ELECTRICAL DEVELOPMENT OF COCHLEAR HAIR CELLS

Johns Hopkins University, Baltimore MD

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Abstract

Cochlear function depends on the specific response properties of the individual sensory hair cells. These receptor cells have a variety of voltage and ligand-gated ion channels which modulate the response to a mechanical stimulus. In the chick's cochlea (basilar papilla) each hair cell's complement of ion channels varies as a function of its position both along and across the tonotopic axis. For example, previous and ongoing work in this laboratory has shown that L-type voltage-gated calcium channels support transmitter release from the hair cells and may vary in number as a function of the afferent innervation density of the cell. Large conductance calcium-activated potassium channels (maxi-K" channels) are associated with voltage-gated calcium channels and can produce electrical tuning in some chick hair cells. Are there cell- specific variations in maxi-K channel kinetics and number as in electrically-tuned hair cells in other species? Further, we've found that maxi-K channels appear uniquely late during embryonic development, coinciding with a time of rapid functional maturation. Do topological and developmental variations in maxi-K channel expression arise by variable gene expression (including mRNA splicing), post-translational modification, or both? Our examination of these questions will take three main forms. First, we have made an important beginning by identification of a candidate gene coding for the maxi-K channel in hair cells. We will attempt to confirm that identity and use it to assess the transcriptional regulation of maxi-K channels both topologically and developmentally. Second, we will continue to examine the cell-specific distribution of maxi-K channels and voltage-gated calcium channels, with a particular emphasis on their possible co-localization at sites of transmitter release from hair cells. Finally, we will examine the role of calcium influx in hair cell maturation by manipulating calcium channel conductance in the embryonic cochlea in vitro.