The outer hair cell, one of the two mechanoreceptor cells in the cochlea, has motility. It is a critical factor for the frequency specificity and for the wide dynamic range of the mammalian ear. Because a mechanosensory cell with motility can exert force responding to mechanical vibration, it can modulate the vibration in the inner ear. For this reason it has been assumed essential for the cell's biological function. The goal of this project is to elucidate the mechanism of this motility. We have been testing our hypothesis 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, realizing direct conversion of electrical energy into mechanical energy. This model predicts voltage and tension dependence of charge transfer, which we experimentally confirmed. We further showed that constraint on the membrane area drastically reduces charge transfer. This observation demonstrates that the motile mechanism resides in the membrane and that it is indeed based on membrane area changes tightly coupled with charge transfer. It was recently shown that the axial stiffness of this cylindrical cell depends on the membrane potential. We showed that the observation is consistent with the model which does not assume stiffness changes in any of its components. That is because the axial stiffness is reduced by conformational transitions of the motor, which depends on both the membrane potential and tension. To clarify the effect of the motile activity of the outer hair cell in the ear, we determined force generation by the cell. The value for isometric force is about 0.1 nN/mV, which agrees with the prediction of the model. To determine the speed of the motile mechanism, we recently examined the frequency spectrum of membrane current noise due to flipping of motor charges. The spectrum is high pass as expected and has the characteristic frequency of about 30 kHz, indicating that is the speed of conformational transitions of the motor. This frequency exceeds 20 kHz, the higher end of the auditory range. These efforts should lead to further clarification of the motility of the outer hair cell and its biological role.
NIH ExPorter
NIH ExPorter