How much prestin motor activity is required for normal hearing?

Prestin (SLC26A5) is a membrane-based voltage-dependent motor protein responsible for outer hair cell (OHC) somatic electromotility. Its importance for mammalian cochlear amplification has been demonstrated using mouse models lacking prestin (prestin-KO) and expressing dysfunctional prestin, prestin^V499G/Y501H (499-prestin-KI). However, it is still not elucidated how prestin contributes to the mechanical amplification process in the cochlea. In this study, we characterized several prestin mouse models in which prestin activity in OHCs was variously manipulated. We found that near-normal cochlear function can be maintained even when prestin activity is significantly reduced, suggesting that the relationship between OHC electromotility and the peripheral sensitivity to sound may not be linear. This result is counterintuitive given the large threshold shifts in prestin-KO and 499-prestin-KI mice, as reported in previous studies. To reconcile these apparently opposing observations, we entertain a voltage- and turgor pressure-based cochlear amplification mechanism that requires prestin but is insensitive to significant reductions in prestin protein expression.