MECHANISM OF OUTER HAIR CELL MOTILITY

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The long-term objective of these studies is to elucidate the mechanism of fast outer hair cell (OHC) motility. The results will be of central interest in basic studies of cochlear mechanism, because they will delineate the capabilities of OHC motility for energy input to the cochlea. This is a necessary precondition for serious theoretical and experimental examination of the role of OHC motility in cochlear function and pathology. An important secondary benefit of these studies is their contribution to cell biology about an extraordinarily fast motility mechanism, one that is unlike anything seen elsewhere to date. Five experimental studies are proposed. Three are designed to test concepts of the mechanism that have been derived from earlier studies and that have been formulated into a comprehensive mathematical model. In this model, motility is thought to be driven by a large number of independently-acting motor molecules located in the membrane of the cell's lateral wall. These "motors" are thought to change conformation in a stochastic voltage-dependent manner. One study will look for evidence of motor conformation changes in the noise statistics of the cell's average length. Another will examine the kinetics of motor activation at speeds not previously technically possible. The motor is believed to act antiphasically in the axial and radial directions. The third proposed study will examine the consistency of this action. A fourth study will determine the force generating capability of the OHC under load. Finally, in a fifth study, OHC motility will be used as an assay to determine the somatic location of voltage-dependent conductances. In addition, the model studies will be extended and new alternative model schemes examined. The model studies will proceed in parallel with and will complement the physiological studies.