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

Area of Science:

• Auditory Neuroscience
• Cellular Electrophysiology
• Mechanobiology of Hearing

Background:

• Cochlear amplification, crucial for hearing's dynamic range, relies on outer hair cell (OHC) electromotility driven by membrane voltage changes.
• OHC membranes' low-pass filtering properties attenuate high-frequency intracellular receptor potentials (RPs), potentially impairing high-frequency hearing.
• Understanding the precise voltage sources driving OHC electromotility across frequencies is vital for explaining cochlear function.

Purpose of the Study:

• To investigate the roles of intracellular receptor potentials (RPs) and extracellular receptor potentials (ERPs) in driving OHC electromotility and cochlear amplification at different frequencies.
• To elucidate the mechanisms underlying high-frequency hearing loss and rescue in specific mouse models.

Main Methods:

• Performed in vivo intracellular and extracellular electrophysiological recordings from the organ of Corti in CBA/J and CD-1 mice.
• Utilized a CD-1 mouse strain transfected with an A88V mutation in connexin 30 to alter gap-junction protein function and membrane resistance.
• Measured basolateral membrane voltages of OHCs across a range of sound frequencies in both wild-type and mutant mice.

Main Results:

• The connexin 30 A88V mutation increased organ of Corti resistance, preserved OHC extracellular receptor potential (ERP) magnitude, and rescued high-frequency hearing.
• This mutation reduced intracellular receptor potentials (RPs) and impaired low-frequency hearing, suggesting differential voltage dependence.
• Extracellular receptor potentials (ERPs), not intracellular RPs, were found to drive OHC motility and cochlear amplification at high frequencies due to lack of frequency attenuation and greater magnitude.

Conclusions:

• Intracellular receptor potentials (RPs) are the primary drivers of OHC motility and cochlear amplification at low frequencies.
• Extracellular receptor potentials (ERPs) are critical for driving OHC motility and cochlear amplification at high frequencies, overcoming the limitations of electrical filtering.
• The study reveals distinct frequency-dependent mechanisms for cochlear amplification mediated by different voltage potentials in outer hair cells.