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

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 Mössbauer 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.

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

“…An ABR threshold elevation between 25 and 50 dB is apparently due to the reduction of the EP (from ~85 mV in WT mice to ~18 mV in heterozygous mice). This is consistent with the level of furosemide-induced reduction of the basilar membrane vibration [12] and threshold elevations in the tuning curves of auditory nerve fibers [13,14]. In homozygous mice, concurrent absence of intermediate cells and the EP further confirms the role of the intermediate cells in generating the EP [2,5,8].…”

“…Those studies demonstrated that, when K + concentration in the endolymph or the EP magnitude is reduced by locally or intravenously applied diuretic compounds such as furosemide [11], basilar membrane vibration is reduced at the characteristic frequency [12], and the threshold of tuning curves of auditory nerve fibers at the characteristic frequency is elevated [13,14]. Interestingly, while the electrochemical environment in the endolymph and the EP maintained by the stria has long been known to be important for hair cell mechanotransduction and cochlear amplification, it is unclear whether reduction or loss of the EP would affect hair cell survival.…”

The Role of Suppression in the Upward Spread of Masking

“…Some (Ruggero and Rich 1991;Ruggero et al 1992;Oxenham and Plack 1997;Gregan et al 1998;Bacon et al 1999;Nelson et al 2001;Yasin and Plack 2003), although not all (Bacon and Viemeister 1985;Murugasu and Russell 1995;Ruggero et al 1997) physiological and psychophysical studies show that the slope of the I/O function or GOM function returns to a value of 1 dB/dB for high-level signals. The implication being that for high-level signals the BM response to both the signal and masker may grow linearly at the signal place, as is the case for low-level signals (Delgutte 1990a;Yates et al 1990).…”

Relating binaural pitch perception to the individual listener’s auditory profile

“…First, most cases of cochlear hearing loss involve damage in outer hair cells (OHCs), whose active mechanism is crucial for a sharp frequency selectivity (Ruggero and Rich, 1991). Asymmetries in OHC damage may also lead to differences in auditory-filter outputs in the two ears.…”