A. James Hudspeth

Our senses of hearing and equilibrium depend upon hair cells, the sensory receptors of the internal ear. A mechanical stimulus applied to such a cell is transduced into an electrical response by the hair bundle, a cluster of 20-300 "feelers" termed stereocilia. The response is then transmitted across a synapse to an afferent fiber of the eighth cranial nerve and thence to the brain. Hair cells are of interest both because of our limited understanding of mechanoelectrical transduction and because their degeneration underlies hearing impairment in 30 million Americans. Dr. Hudspeth and his associates have demonstrated that mechanical stimuli directly activate cation-permeable ion channels near the stereociliary tips. Shear between adjacent stereocilia stretches the tip link, a fine filament connecting them; tension in the tip link then opens the molecular gate of a transduction channel. The group has shown that individual hair cells are electrically tuned to specific frequencies by the interaction between calcium and potassium channels. The latter occur in a wide variety of forms, generated by alternative mRNA splicing, whose varied physiological properties underlie the cells' different frequency responsiveness. The investigators have recently begun to study the constituents of hair cells at a biochemical, molecular-biological, and developmental level.