The sensory and motor roles of auditory hair cells

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Abstract
Sound vibrations conducted to the cochlea are detected by inner and outer hair cells. Both types of hair cell transduce sound stimuli through minute displacements of their hair bundle, an array of modified microvilli known as stereocilia that project from their apical surface. Outer hair cells, unlike inner hair cells, have a further role in generating force, known as the cochlear amplifier, which mechanically boosts the sound-induced vibrations and augments frequency tuning. Two mechanisms of force generation have been advanced: contractions of the cell soma and active motion of the hair bundle. Many proteins found in the mechanosensory hair bundle have been isolated by studies of genetic mutations that cause deafness. Crucial proteins for hair bundle development and function include many myosin isoforms. Myosin XVa is localized to the tips of the stereocilia and might regulate the rate of actin incorporation, and thereby specify stereociliary length. Myosin VIIa might control the interciliary linkages, whereas myosin 1c is proposed to modulate the force on the mechanotransducer channel imposed by stretch of the tip links. Deflections of the hair bundle are detected by mechanoelectrical transduction (MET) channels, which are located at the tips of stereocilia and activated by tension in the tip links. The most likely candidate for the MET channels is a transient receptor potential (TRP) channel, possibly TRPA1, which has large unitary conductance and is highly permeable to Ca2+. Elevation of intracellular Ca2+ by influx of the ion through MET channels controls adaptation by various routes, including fast channel re-closure and slower control of the force imposed on the channel through myosin 1c. Fast adaptation of the MET channels occurs on a submillisecond timescale. Hair cells tuned to higher frequencies have MET channels with larger single-channel conductance, permitting a larger Ca2+ influx and faster adaptation matched to the frequency detected by the hair cell. One mode of force generation by outer hair cells occurs by voltage-dependent contractions of the cell soma attributable to the chloride-binding protein prestin. However, prestin might not operate on a cycle-by-cycle basis at high frequencies because the receptor potential is attenuated by the membrane time constant. Recent results indicate that changes in MET channel gating attributable to fast adaptation cause force generation by the hair bundle that could supplement prestin-driven somatic contractions. Prestin's role might then be to act as another form of adaptation, continuously resetting the operating range of the MET channels to maintain them in their most sensitive position.