Comparison of the non-adrenergic action of phentolamine with that of vanadate on cochlear function

Two drugs, which upon superficial examination appeared to be acting on common processes, have been found upon closer investigation to act by quite different means. Both act primarily at the organ of Corti, causing a pronounced increase of the endocochlear potential and a depression of the cochlear microphonic (CM). These effects are accompanied by the elimination of a negative component of the EP; however, it was found that these three effects are produced by phentolamine in scala media (or, more slowly, in scala tympani) but by vanadate only in scala tympani. This difference in locus of action is manifested further by different changes of the summating potential (SP): phentolamine has little effect on the magnitude of SP^-, while vanadate leads to an elevated SP^-. In spite of this difference in the 'zeroth order harmonic', the second harmonic of the CM is depressed by both agents. It is argued that phentolamine may act either by blocking the acoustically-modulated ion channels in the luminal membranes of the hair cells or by inducing a large, non-selective, paracellular conductance in the organ of Corti. The present results, in conjunction with our previous results (Marcus D.C., DeMott J.E., Kobayashi T., Ge X.-X. and Thalmann R. (1981): Hearing Res. 5, 231-243), are further interpreted as suggesting that vanadate may initially act by depolarizing the hair cells.