Human otosclerotic bone-derived peptide decreases the gain of the electromotility in isolated outer hair cells.

An otosclerotic peptide (OP) (Sziklai et al., 1985a.b) was purified from perilymph and stapes footplate of otosclerotic patients by Sephadex G-25 gel column chromatography and subsequent isotachophoretic (ITP) separation. The transfer function of the electromotility was measured by inserting the isolated outer hair cells (OHC) into a partitioning microchamber (Evans et al., 1991) and applying a series of pairs of brief square-pulse stimuli with opposite polarity and with increasing magnitude. Somatic length changes of the inserted part of the OHCs were measured by an optoelectronic system. The isotachophoretically homogeneous peptide exerted a gain and magnitude decreasing effect on the transfer function of electromotility of isolated OHCs of the guinea pig, in vitro. The operating point of the electromotility did not change due to the effect of the peptide. The peptide decreased the electromotile performance within a minute and bath exchange to normal saline did not completely restore the transfer curve to baseline. Application of caffeine to the cells already under the effect of the otosclerotic peptide produced an opposite effect: gain and magnitude increase. Simultaneous application of acetylcholine (ACh) did not antagonize the effect of OP. The underlying mechanism of the action of OP on the transfer function of electromotility of OHCs is postulated to involve the modulation of intracellular Ca2- concentration.