Two models representing the events after anion binding to prestin. The left panel depicts the extrinsic voltage sensor model (21), where Cl− binds and enters the defunct transporter, which in turn triggers an extension of prestin. The right panel depicts the intrinsic voltage sensor model (23–25), where Cl− binding to prestin allosterically promotes the contracted state, but voltage sensing results from movement of intrinsically charged amino acid residues (red: positive residues; black: negative residues) (26). Our new data confirm that during expansion, anions are released from prestin. (In both panels, d is the perpendicular distance traversed across the membrane field by the voltage sensor.)