EFFECTS OF SALICYLATE AND LANTHANIDES ON OUTER HAIR CELL MOTILITY ANDASSOCIATED GATING CHARGE

Salicylate, one of the most widely used drugs, is known to induce reve rsible tinnitus and hearing loss. Salicylate interferes with outer hai r cells (OHCs), which are believed to underlie normal auditory frequen cy selectivity and sensitivity. In the present experiments, the effect s of salicylate and lanthanides on OHC motility and nonlinear capacita nce were investigated by using isolated guinea-pig OHCs while attempti ng to avoid inadvertent intracellular pressure change, which itself ca n affect OHC motility and capacitance. Either extracellularly or intra cellularly applied salicylate reduced nonlinear peak capacitance (Cm-p k) and shifted the voltage at peak capacitance to depolarized levels. Concentration-response curves for reduction in Cm-pk by salicylate and GdCl3 revealed a half-maximal concentration and Hill coefficient of 1 .6 mM and 1.0, and 0.6 mM and 1.2, respectively. In comparable groups of OHCs, the normal Cm-pk values of which were near 40 pF, average Cm- pk decreased to 28 and 36 pF for intracellularly and extracellularly a pplied salicylate, respectively. Salicylate reduced, but did not compl etely block, the voltage-induced length change. Extracellularly, but n ot intracellularly, applied lanthanide blocked voltage-induced movemen t and capacitance almost completely. After intracellular trypsin treat ment, salicylate reduced voltage-dependent capacitance reversibly, sug gesting that salicylate directly acts on the sensor/motor and not via effects on intracellular structures, such as the subsurface cisternae. The results are consistent with the hypothesis that the dissociated, charged form of salicylate directly interacts with the sensor/motor on the inner aspect of the OHC plasma, whereas lanthanides interact on t he outer aspect.