The effects of intracochlear and systemic furosemide on the properties of single cochlear nerve fibres in the cat

Abstract

SUMMARY1. Tuning properties and spontaneous discharge rate of single cochlear fibres in the anaesthetized cat were determined during short-and long-term poisoning of the cochlea by locally and systemically applied furosemide.2. With intra-arterial administration offurosemide, short-term reversible elevation occurred of the low threshold sharply tuned 'tip' segment of the frequency threshold ('tuning') curve (f.t.c.) by up to 40 db, without substantial changes in the threshold of the low frequency 'tail' segment of the f.t.c. These changes could occur in part without changes in the spontaneous activity and entirely without changes in the maximal evoked activity. These effects were observed in all fibres examined, the characteristic frequencies of which ranged from 3-5 to 31 kHz.3. Intracochlear administration of furosemide in 0-9 mm concentrations produced similar changes, but these were not reversible.4. The changes correlated with the depression of the amplitude of the gross cochlear action potential. The cochlear microphonic potential, however, was either unchanged, or only slightly reduced.5. In long-term furosemide poisoning of the cochlea, fibres with anomalous response properties were found alongside fibres having normal tuning. The former exhibited either reduced excitability of the low threshold tip segment, or a tip segment attenuated in both excitability and threshold.6. It is concluded that the selective effects of furosemide on the tip segment of cochlear fibre f.t.c.s offer further evidence for a physiologically vulnerable 'second filter' in the cochlea. The selective influence of the furosemide on the low threshold tip segment provides support for the hypothesis that the normal f.t.c. is generated by two largely independent processes: one vulnerable, low threshold and sharply tuned, and the other less vulnerable, but high threshold and more broadly tuned.7. The findings, obtained with an agent known to produce reversible impairment of hearing in man, provide direct physiological evidence in support of the hypothesis that in sensorineural hearing loss of cochlear origin the frequency selectivity of cochlear nerve fibres is impaired.

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.…”

Accuracy of velocity distortion product otoacoustic emissions for estimating mechanically based hearing loss

“…Consistent with this observation, furosemide reduces DPOAE amplitude and DPOAE threshold (Mills et al, 1993;Mills and Rubel, 1994;Mills and Schmiedt, 2004;Mills, 2003Mills, , 2006Rübsamen et al, 1995). Apart from reducing the receptor potential of both OHCs and IHCs, EP reduction hyperpolarises the resting membrane potential (Sewell, 1984b), which results in substantial reduction of the spontaneous activity and discharge rate of the auditory nerve fibres (Evans and Klinke, 1982;Sewell, 1984b,c) and, subsequently, in an elevation of neural threshold (Evans and Klinke, 1982;Sewell, 1984a;Rübsamen et al, 1995). These findings suggest that the loss of CAP threshold observed here, following furosemide application, is the consequence of concomitant alteration of the function of both the OHCs and the IHCs.…”

Passive exposure of adult cats to moderate-level tone pip ensembles differentially decreases AI and AII responsiveness in the exposure frequency range

“…There is no doubt that the almost two-octave gap between the 4 and 16 kHz bands could be resolved perceptually given the sharp frequency selectivity of cat basilar membrane (Cooper and Rhode, 1992), auditory nerve fiber (e.g., Kiang et al, 1965;Evans and Klinke, 1982), and AI neuron (Phillips and Irvine, 1981) responses, even at the stimulus levels used here. If the response suppression in AI was the product of an active habituation to the exposure Fig.…”