Abstract
The cochlea’s high sensitivity stems from the active process of outer hair cells, which possess two force-generating mechanisms: active hair-bundle motility elicited by Ca2+ influx and somatic motility mediated by the voltage-sensitive protein prestin. Although interference with prestin has demonstrated a role for somatic motility in the active process, it remains unclear whether hair-bundle motility contributes in vivo. We selectively perturbed the two mechanisms by infusing substances into the endolymph or perilymph of the chinchilla’s cochlea and then used scanning laser interferometry to measure vibrations of the basilar membrane. Blocking somatic motility, damaging the tip links of hair bundles, or depolarizing hair cells eliminated amplification. While reducing amplification to a lesser degree, pharmacological perturbation of active hair-bundle motility diminished or eliminated the nonlinear compression underlying the broad dynamic range associated with normal hearing. The results suggest that active hair-bundle motility plays a significant role in the amplification and compressive nonlinearity of the cochlea.
Content
The sense of hearing excels in several ways. Human hearing spans the enormous frequency range from 20 Hz to 20 kHz, yet we can distinguish frequencies that are only 0.2% apart. This interval is well below a semitone in Western music, which represents about 6% in frequency. Moreover, humans can perceive trillionfold differences in sound intensity, yet the faintest detectable sounds vibrate the tympanic membrane by only 10 pm. These extraordinary features ensue from an active process that provides tuned mechanical amplification of weak signals in the mammalian cochlea. Stimulation with a pure tone elicits a wave of basilar-membrane motion that travels apically and peaks at a frequency-dependent position: high frequencies evoke a maximal response near the cochlear base and progressively lower frequencies at successively more apical positions (1-4). As a traveling wave advances, the active process of outer hair cells continuously adds energy to the vibration to counter the dissipative effect of viscosity (5-7).
The molecular basis of the active process remains unclear. The outer hair cells of mammals exhibit a unique form of mechanical activity: their cell bodies change in length when the membrane potential is altered (8, 9). This somatic motility or electromotility is produced by the membrane protein prestin, which undergoes conformational changes upon alteration of the membrane potential (10). Several experimental studiesdemonstrate that somatic motility is required for the active process in the cochlea. Transgenic mice in which prestin has been incapacitated or eliminated display severely elevated hearing thresholds (11-14). In wild-type animals, targeted inactivation of prestin over cochlear segments near a traveling wave’s peak dramatically reduces the gain (15).
