This finding is consistent with observations that the intact cochlear partition is roughly three orders of magnitude stiffer than an individual outer hair cell (He and Dallos, 1999; Olson and Mountain, 1991). A portion of the active process remained after photoinactivation of regions in which gain occurred, however, for damping increased even further after anoxia (Figures 4A and 4B). Although

the residual active process might reflect incomplete blockage of prestin, we ascertained that repeated exposure to UV light in the presence of 4-azidosalicylate did not further diminish the response (Figure 3D). Understanding the degree to which photoinactivation eliminates electromotility selleck kinase inhibitor in vivo could yield a more quantitative assessment of prestin’s contribution to amplification. Obtaining a clearer picture of the intact

active process would also necessitate an appreciation of the specificity with which photoinactivation affects electromotility; are other cellular processes affected? If, for example, active hair-bundle motility were entirely spared the effects of photoinactivation, then bundle forces might account for the balance of amplification. It is possible, however, that photoinactivating prestin affected hair-bundle forces as well. Changes in an outer hair cell’s membrane potential can elicit hair-bundle deflections (Jia and He, 2005). Moreover, hair bundles can Selleck Target Selective Inhibitor Library be displaced by somatic length changes of outer hair cells through the mechanical coupling in an intact organ of Corti. Although adaptation in hair bundles restores the set point of nonlinear amplification even for large static deflections (Martin et al., 2003), photoinactivation might force all prestin molecules into a conformation normally elicited only by extreme depolarization. In this circumstance, active hair-bundle motility could be compromised. Finally, salicylate might affect other aspects of hair-cell physiology. Although we failed to detect photolabeling of other proteins during our biochemical investigation, it remains possible that photoinactivation

modifies proteins in addition to prestin. Cell press These results demonstrate that an active process overcomes viscous damping to locally amplify the cochlear traveling wave and that this locally accrued gain accumulates spatially up to the wave’s peak. The results further indicate that prestin plays a crucial role in establishing this gain. It remains an open question, however, how this active process is locally tuned to yield a tonotopic map of amplification. Despite its critical contribution, there is no evidence yet that somatic motility exhibits resonance. Under physiological conditions, sound-evoked receptor potentials in mammalian outer hair cells modulate a resting potential of −40 mV by less than 10 mV at moderate stimulus levels (Johnson et al., 2011; Kössl and Russell, 1992).