The sensitivity and selectivity of the human hearing organ rely on amplification of vibrations in the cochlea. Variation of the length of outer hair cells (OHC) in the cochlea in response to changes in transmembrane potential is central to sound amplification. But how do OHC change their length? Last year, prestin — a novel member of the family of pendrin-related transporters, found in the lateral membrane of OHC — was discovered to be the 'motor protein' responsible for OHC electromotility. Now, Oliver and colleagues report in Science that intracellular anions are the voltage sensor of prestin.

When sound travels through the cochlea, vibrations deflect the cilia on the apical side of OHC, opening mechano-sensitive ion channels. The resulting change in membrane potential induces cell lengthening in the case of hyperpolarization or shortening if the cell is depolarized. The motile response of OHC is accompanied by prestin-dependent charge movement, which can be measured experimentally.

Oliver and colleagues first assumed that a charged amino acid in prestin is likely to underlie the measured charge movement. They mutated the most likely candidates to non-charged residues and measured the gating current, but the characteristic bell-shaped electrical signature was not affected by any of these mutations.

The authors then reasoned that if the voltage sensor is not part of prestin, maybe it is an extrinsic charged particle. They tested intra- and extracellular ions and found that the charge movement is in fact due to the movement of cytosolic Cl− or HCO3− ions across the membrane in response to changes in membrane potential.

A model emerges from this study. Many prestin molecules are embedded in the lateral membrane of OHC. When the transmembrane potential changes, it induces movement of intracellular anions into, or out of, a pocket in prestin, causing a switch between a wide and a narrow conformation. If all prestin molecules are in the narrow conformation, the cell shortens, whereas if they are in the wide conformation, the cell lengthens. From a cell biologist's point of view, prestin is an unusual 'motor protein', as it doesn't move relative to an anchorage point but rather changes the volume that it takes up within the plasma membrane, thereby indirectly changing the surface, and hence the length, of the cell.