The outer hair cell, a mechanoreceptor cell in the cochlea, is a critical factor for fine tuning and for the wide dynamic range of the mammalian ear. This cell has an unusual motility at its cell body, which is consistent with the function of modulating the sensitivity. The goal of this project is to elucidate the mechanism of the motility. We have earlier hypothesized that the motor has a charge transferable across the membrane and that charge transfer is coupled with changes in the membrane area of the motor. Such a mechanism enables conversion of electrical energy into mechanical energy. This model predicts voltage and tension dependence of charge transfer, which we experimentally confirmed. We further tested our hypothesis by constraining the membrane area using inflated cells that were internally treated with trypsin. We found that constraint on the membrane area drastically reduces charge transfer. Our observations demonstrated that the motile mechanism is indeed based on membrane area changes tightly coupled with charge transfer. They also indicated that the unit of the motor is in the plasma membrane. This motile mechanism is consistent with our model earlier proposed to describe the motility of the intact cell, which predicted force generation of 0.1 nN/mV for a single cell, agreeing with our experiment. The motor mechanism in the outer hair cell is unique not only in energy source, it is also unique in the speed of the response, which apparently exceeds 10 kHz. We recently formulated a kinetic theory predicting that the intrinsic speed of the membrane motor can be determined by the frequency dependence of membrane noise due to flipping of motor charges. Our preliminary observation confirmed that flipping of individual charge takes place at high rates. It also confirmed that the unit of charge that flips is equivalent of about one electron, confirming the validity of earlier estimates based on static observations. These efforts should lead to further clarification of the motility of the outer hair cell and its biological role. - hair cell, patch clamp, motor, membrane capacitance, membrane potential, membrane elasticity, cytoskeleton, noise spectrum
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