Effects of perilymphatically perfused gentamicin on microphonic potential, lipid labeling and morphology of cochlear tissues.

The perilymphatic space of the guinea pig was perfused in situ with artificial perilymph containing [32P] orthophosphate and 3H-glycerol while cochlear microphonic potentials (CM) were monitored. The perfusion of 10 mM gentamicin suppressed CM by 62% within 30 min. 32P-incorporation into phosphatidylinositol bisphosphate in the organ of Corti was decreased but distribution of 3H-glycerol in neutral lipids and phospholipids was not affected by gentamicin. The morphological evaluation included all structures lining the scala media, the spiral ligament, the basal membrane and the vestibular organs. Hair cells sometimes contained small intracellular 'precipitation' lines but, in general, ultrastructure of all tissues was essentially normal and no overt histopathological changes were evident. The observed biochemical changes should, therefore, represent early and primary actions of the drug. This confirms the hypothesis that an interaction with the acidic phospholipid, phosphatidylinositol bisphosphate, is an important step in the ototoxic mechanism of amino-glycoside antibiotics.