A Gap-Junction Mutation Reveals That Outer Hair Cell Extracellular Receptor Potentials Drive High-Frequency Cochlear Amplification

Cochlear amplification enables the enormous dynamic range of hearing through amplifying cochlear responses to low-to moderate-level sounds and compressing them to loud sounds. Amplification is attributed to voltage-dependent electromotility of mechanosensory outer hair cells (OHCs) driven by changing voltages developed across their cell membranes. At low fre-quencies, these voltage changes are dominated by intracellular receptor potentials (RPs). However, OHC membranes have electrical low-pass filter properties that attenuate high-frequency RPs, which should potentially attenuate amplification of high-frequency cochlear responses and impede high-frequency hearing. We made in vivo intracellular and extracellular elec-trophysiological measurements from the organ of Corti of male and female mice of the CBA/J strain, with excellent high -fre-quency hearing, and from the CD-1 mouse strain, which has sensitive hearing below 12 kHz but loses high-frequency hearing within a few weeks postpartum. The CD-1 mouse strain was transfected with an A88V mutation of the connexin 30 gap -junc-tion protein. By blocking the action of the GJ protein to reduce input resistance, the mutation increased the OHC extracellu-lar RP (ERP) magnitude and rescued high-frequency hearing. However, by increasing the organ of Corti resistance, the mutation rescued high-frequency hearing through preserving the OHC extracellular RP (ERP) magnitude. We measured the voltage developed across the basolateral membranes of OHCs, which controls their electromotility, for low-to high-frequency sounds in male and female mice of the CD-1 strain that expressed the A88V mutation. We demonstrate that ERPs, not RPs, drive OHC motility and cochlear amplification at high frequencies because at high frequencies, ERPs are not frequency atte-nuated, exceed RPs in magnitude, and are appropriately timed to provide cochlear amplification.

Automated summary

Cochlear amplification is achieved through the voltage-dependent electromotility of mechanosensory outer hair cells, which amplifies low-to-moderate level sounds and compresses loud sounds. This study investigates the role of receptor potentials and electrical properties of outer hair cells in high-frequency hearing. The results suggest that extracellular receptor potentials, rather than receptor potentials, drive outer hair cell motility and cochlear amplification at high frequencies.