Electrical control of the transduction channels’ gating force in sensory hair cells
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Hair cells, the sensory receptors of the inner ear, rely on mechanosensitive ion channels to transduce mechanical vibrations of their hair bundle into electrical signals. The mechanical correlate of channel gating—the gating force—is a fundamental determinant of hair-cell mechanosensitivity to displacements of the hair bundle. We report here the effects of varying the electrical potential across the epithelium that houses the hair cells on the gating force. We found that a negative potential in the endolymph that bathed the hair bundles increased the gating force by up to twofold, while positive endolymphatic potentials had the opposite effect. In contrast, the endolymphatic potential only weakly affected hair-bundle stiffness. Together, our results indicate that the gating force varied because the gating swing varied, from values that are comparable to the pore size of the transduction channels to values nearly tenfold as large. When the endolymphatic potential reached a negative threshold value of about −50 mV, our work further revealed a reversible, but hysteretic, transition between states of strong and weak gating force, for which the hair bundles oscillated spontaneously or remained quiescent, respectively. Finally, we provide evidence that these effects resulted from a modulation of the Ca 2+ influx through the transduction channels and that a minimal influx is necessary to produce strong gating forces. We propose that force sensitivity of the transduction channel protein complex can be adjusted by the hair cell depending on physiological control parameters.
SIGNIFICANCE STATEMENT
The inner ear’s hair cells rely on mechanosensitive ion channels to convert vibrations of their hair bundles into electrical signals. We show that varying the electrical potential across the sensory hair-cell epithelium continuously modulates a fundamental determinant of mechanosensitivity called the gating force. Remarkably, a hair cell can also switch between states of weak and strong gating force at negative potentials, so that strong gating forces associated to high mechanosensitivity are observed only when the calcium influx through the channels is large enough, but not too large. Gating-force control is expected to underly the ear’s ability to achieve exquisite mechanosensitivity to minute sound stimuli and be relevant to biological systems relying on direct mechanical gating of ion channels.