THEORY OF ELECTRICALLY DRIVEN SHAPE CHANGES OF COCHLEAR OUTER HAIR-CELLS

1. A theory of cochlear outer hair cell electromotility is developed a nd specifically applied to somatic shape changes elicited in a microch amber. The microchamber permits the arbitrary electrical and mechanica l partitioning of the outer hair cell along its length. This means tha t the two partitioned segments are stimulated with different input vol tages and undergo different shape changes. Consequently, by imposing m ore constraints than other methods, experiments in the microchamber ar e particularly suitable for testing different theories of outer hair c ell motility. 2. The present model is based on simple hypotheses. They include a distributed motor associated with the cell membrane or cort ex and the assumption that the displacement generated by the motor is related to the transmembrane voltage across the associated membrane el ement. It is expected that the force generated by the motor is counter balanced by an elastic restoring force indigenous to the cell membrane and cortex, and a tensile force due to intracellular pressure. It is assumed that all changes take place while total cell volume is conserv ed. The above elements of the theory taken together permit the develop ment of qualitative and quantitative predictions about the expected mo tile responses of both partitioned segments of the cell. Only a DC tre atment is offered here. 3. Both a linear motor and an expanded treatme nt that incorporates a stochastic molecular motor model are considered . The latter is represented by a two-state Boltzmann process. We show that the linear motor treatment is an appropriate extrapolation of the stochastic motor theory for the case of small voltage driving signals . Comparison of experimental results with model responses permits the estimation of model parameters. Good match of data is obtained if it i s assumed that the molecular motors undergo conformational length chan ges of 0.7-1.0 nm, that they have an effective displacement vector at approximately -20-degrees with the long axis of the cell, and that the ir linear density is approximately 80/mum. 4. An effort is made to par cel out motile response components that are a direct consequence of th e motor action from those that are mediated by cytoplasmic pressure ch anges brought about by the concerted action of the motors. We show tha t pressure effects are of minor importance, and thus rule out models t hat rely on radial constriction / expansion-mediated internal pressure change as the primary cause of longitudinal motility. 5. As a consequ ence of the interaction between the Boltzmann process and the mechanic al characteristics of the cell, the electro-motile response is asymmet ric. It is shown that axial displacement is always greater in the cont raction direction, whereas radial displacement is always greater in th e expansion direction. These results are in full accord with experimen tal observations. The treatment is extended to consider the effects on motility of changing membrane potential, and its significant influenc e on the cell's nonlinear responsiveness is demonstrated. We show that modest depolarization produces a linearization of the response, where as severe depolarization results in a reversal of response asymmetry. 6. The relevance of the results to putative in vivo outer hair cell mo tility is considered.