Regulation of cochlear outer hair cells: Insights from mathematical modelling

Abstract

The outer hair cells (OHCs) of the cochlea are the source of much of our exquisite auditory sensitivity, providing sharp mechanical tuning and increasing the vibration of the basilar membrane by up to a factor of 1000. They accomplish this by a combination of mechanoelectrical and electromechanical transduction – providing positive feedback to enhance sound-induced vibration and cancel friction. Because the OHCs are sensitive to displacements of molecular dimensions, and yet are motile themselves, they must employ a number of negative-feedback (homeostatic) mechanisms to regulate their sensitivity in the face of daily disturbances. To understand some of these mechanisms, we have created a mathematical model of OHC, focusing on the links between ion transport, electrophysiology and OHC motility. The model we present offers insights into the regulation of OHC membrane potential and mechanoelectrical transduction, and provides a physiologically-plausible and internally-consistent explanation for the time-courses of the cochlear changes we have observed during different experimental perturbations performed in the guinea pig cochlea. We show how the known ionic mechanisms within OHCs act to regulate membrane potential and hair bundle angle over a very wide range of electrical and hydrostatic conditions, and are responsible for a slow oscillatory behaviour (also present in humans) that we presume is due to oscillations in cytosolic calcium concentration.