Distortion component analysis of outer hair cell motility-related gating charge

The underlying Boltzmann characteristics of motility-related gating current s of the outer hair cell (OHC) are predicted to generate distortion compone nts in response to sinusoidal transmembrane voltages. We studied this disto rtion since it reflects the mechanical activity of the cell that may contri bute to peripheral auditory system distortion. Distortion components in the OHC electrical response were analyzed using the whole-cell voltage clamp t echnique, under conditions where ionic conductances were blocked. Single or double-sinusoidal transmembrane voltage stimulation was delivered at vario us holding voltages, and distortion components of the current responses wer e detected by Fourier analysis. Current response magnitude and phase of eac h distortion component as a function of membrane potential were compared wi th characteristics of the voltage-dependent capacitance, obtained by voltag e stair-step transient analysis or dual-frequency admittance analysis. The sum distortion was most prominent among the distortion components at all ho lding voltages. Notches in the sum (f1+f2), difference (f2-f1) and second h armonic (2f) components occur at the voltage where peak voltage-dependent c apacitance resides (V-pkCm). Rapid phase reversals also occurred at V-pkCm, but phase remained fairly stable at more depolarized and hyperpolarized po tentials. Thus, it is possible to extract Boltzmann parameters of the motil ity-related charge movement from these distortion components. In fact, we h ave developed a technique to follow changes in the voltage dependence of OH C motility and charge movement by tracking the voltage at phase reversal of the f2-f1 product. When intracellular turgor pressure was changed, V-pkCm and distortion notch voltages shifted in the same direction. These data hav e important implications for understanding cochlear nonlinearity, and more generally, indicate the usefulness of distortion analysis to study displace ment currents.