Chlorpromazine alters outer hair cell electromotility

OBJECTIVE: Outer hair cells (OHCs) of the inner ear rapidly convert electri cal gradients into mechanical force, enhancing cochlear sensitivity and fre quency selectivity. We investigated the effect of chlorpromazine, an antips ychotic medication that alters membrane biomechanics, on OHC electromotilit y. STUDY DESIGN: Isolated guinea pig outer hair cells were perfused with chlor promazine under whole-cell patch-pipette recording conditions. Electromotil e responses were measured. RESULTS: A dramatic, reversible, dose-dependent depolarization of voltage a t peak capacitance (V-pkCm) was seen with chlorpromazine treatment. The gai n of the electromotile response was maximal near V-pkCm both before and aft er chlorpromazine application. Unlike the 3 other agents that alter electro motility (salicylate, lanthanides, membrane tension), chlorpromazine did no t change peak capacitance (Cm-pk), which varies directly with maximal elect romotile gain. CONCLUSION: Chlorpromazine changes the membrane voltage at which OHCs exhib it maximal electromotile gain, without changing the magnitude of electromot ile responses. SIGNIFICANCE: Chlorpromazine may diminish hearing thresholds or otoacoustic emissions in large doses.