Maturation of Voltage-induced Shifts in SLC26a5 (Prestin) Operating Point during Trafficking and Membrane Insertion

Prestin (SLC26a5) is an integral membrane motor protein in outer hair cells (OHC) that underlies cochlear amplification. As a voltage-dependent protein, it relies on intrinsic sensor charge to respond to transmembrane voltage (receptor potentials), thereby effecting conformational changes. The protein's electromechanical actively is experimentally monitored as a bell-shaped nonlinear capacitance (NLC), whose magnitude peaks at a characteristic voltage, V_h. This voltage denotes the midpoint of prestin's charge-voltage (Q-V) Boltzmann distribution and region of maximum gain of OHC electromotility. It is an important factor in hearing capabilities for mammals. A variety of biophysical forces can influence the distribution of charge, gauged by shifts in V_h, including prior holding voltage or membrane potential. Here we report that the effectiveness of prior voltage augments during the delivery of prestin to the membranes in an inducible HEK cell line. The augmentation coincides with an increase in prestin density, maturing at a characteristic membrane areal density of 870 functional prestin units per square micrometer, and is likely indicative of prestin-prestin cooperative interactions.