Intracellular anions as the voltage sensor of prestin, the outer hair cellmotor protein

Outer hair cells (OHCs) of the mammalian cochlea actively change their cell Length in response to changes in membrane potential. This electromotility, thought to be the basis of cochlear amplification, is mediated by a voltag e-sensitive motor molecule recently identified as the membrane protein pres tin. Here, we show that voltage sensitivity is conferred to prestin by the intracellular anions chloride and bicarbonate. Removal of these anions abol ished fast voltage-dependent motility, as well as the characteristic nonlin ear charge movement ("gating currents") driving the underlying structural r earrangements of the protein. The results support a model in which anions a ct as extrinsic voltage sensors, which bind to the prestin molecule and thu s trigger the conformational changes required for motility of OHCs.