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

1. 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 of furosemide, 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.