Furosemide alters organ of corti mechanics: evidence for feedback of outer hair cells upon the basilar membrane

TLDR

The mechanical response of the basilar membrane to sound is thought to depend on outer hair cell transduction. The study aimed to test whether outer hair cell transduction affects basilar membrane mechanics by administering furosemide. Basilar membrane vibrations were recorded with Mossbauer spectroscopy or Doppler‑shift laser velocimetry following systemic furosemide injection. Furosemide reversibly diminished basilar membrane responses to tones and clicks, with reductions up to 61 dB at low intensities near the characteristic frequency and phase lags up to 77°, confirming that outer hair cells are essential for high sensitivity and frequency selectivity and indicating that outer hair cell loss leads to reduced basilar membrane vibrations in sensorineural hearing loss.

Abstract

A widely held hypothesis of mammalian cochlear function is that the mechanical responses to sound of the basilar membrane depend on transduction by the outer hair cells. We have tested this hypothesis by studying the effect upon basilar membrane vibrations (measured by means of either the Mossbauer technique or Doppler-shift laser velocimetry) of systemic injection of furosemide, a loop diuretic that decreases transduction currents in hair cells. Furosemide reversibly altered the responses to tones and clicks of the chinchilla basilar membrane, causing response-magnitude reductions that were largest (up to 61 dB, averaging 25–30 dB) at low stimulus intensities at the characteristic frequency (CF) and small or nonexistent at high intensities and at frequencies far removed from CF. Furosemide also induced response-phase lags that were largest at low stimulus intensities (averaging 77 degrees) and were confined to frequencies close to CF. These results constitute the most definitive demonstration to date that mechanical responses of the basilar membrane are dependent on the normal function of the organ of Corti and strongly implicate the outer hair cells as being responsible for the high sensitivity and frequency selectivity of basilar membrane responses. A corollary of these findings is that sensorineural hearing deficits in humans due to outer hair cell loss reflect pathologically diminished vibrations of the basilar membrane.