The membrane based electromechanics of inner ear hair cell stereocilia

Hair cells of the inner ear are the primary sensors responsible for detection of sound and balance. At their apex, hair cells have a bundle of modified microvilli, stereocilia, that give these cells their name. During mechanotransduction, depolarizing current enters through a mechanically gated ion channel located near the tip of the stereocilium resulting in an influx of current at the apex of the soma. This leads to synaptic vesicle binding and the release of neurotransmitter to modulate the discharge of afferents within the eighth cranial nerve. The long and slender geometry suggests that stereocilia act as low-pass filters due to their electrical cable properties, and as electromechanical motors due to their flexoelectric membrane properties. This dissertation begins with an examination of the passive electrical characteristics of hair cell stereocilium using a biophysically realistic model based on Lord Kelvin's cable theory. We present expected capacitance magnitudes of individual stereocilia and combined bundles. Further, under voltage-clamp conditions, we demonstrate that the variable conductance at the stereocilia tip causes a compromise in the "space-clamp" leading to a decrease in the measured capacitance and the potential for errors in data interpretation. Next, the dissertation examines the active electro-mechanical amplification of stereocilium bundles. We present new work indicating that membrane flexoelectricity of stereocilia contributes to the amplification process through the conversion of input mechanotransduction electrical power to output mechanical power. Results show that the phylogenic relationship between stereocilium height, the optimal frequency of sensation, and the ensuing tonotopic gradation in bundle height promote optimum efficiency of this power conversion. Finally, the manifestation of flexoelectric-induced membrane deformation was further investigated to illustrate its influence on hair bundle motion. Toward this end, a numerical model of the hair bundle was composed using morphological and physiological data from frog saccular hair cells to investigate the contribution of flexoelectricity to hair bundle kinematics and kinetics. Overall, results demonstrate the potential importance of stereocilia electrical cable properties and membrane flexoelectricity in key biophysical properties of sensory hair cells.