Cochlear amplification, whereby cochlear responses to low-to-moderate sound levels are 31 amplified and compressed to loud sounds, is attributed to outer hair cell (OHC) electromotility 32 driven by voltage changes across the OHC basolateral membranes due to sound-induced 33 receptor-current modulation. Cochlear operation at high acoustic frequencies is enigmatic 34 because the OHC intracellular receptor potential (RP) is severely attenuated at these 35 frequencies. Clues to understanding the voltage control of OHC electromotility at different 36 frequencies was provided by measurements from CD-1 mice with an A88V mutation of the 37 gap-junction (GJ) protein connexin 30 (Cx30), which with Cx26, form heterogeneous GJs 38 between supporting cells in the organ of Corti (OoC) and stria vascularis. The A88V mutation 39 results in a smaller GJ conductance which may explain why the resistance across the OoC in 40 CD-1Cx30A88V/A88V mutants is higher compared with wild-type mice. The endocochlear 41 potential, which drives the OHC receptor current and, consequently, the OHC RPs, is smaller 42 in CD-1Cx30A88V/A88V mutants. Even so, their high-frequency hearing sensitivity equals that of 43 wild-type mice. Preservation of high-frequency hearing correlates with similar amplitude of 44 extracellular receptor potentials (ERPs), measured immediately adjacent to the OHCs. ERPs 45 are generated through OHC receptor current flow across the OoC electrical resistance, which 46 is larger in CD-1Cx30A88V/A88V than in wild-type mice. Thus, smaller OHC receptor currents 47 flowing across a larger OoC resistance in CD-1Cx30A88V/A88V mice may explain why their ERP 48 magnitudes are similar to wild-type mice. It is proposed that the ERPs, which are not subject 49 to low-pass electrical filtering, drive high-frequency cochlear amplification.
A gap-junction mutation in the mouse cochlea reveals cochlear amplification is driven by outer hair cell extracellular receptor potentials
