Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear

Significance In this work, we developed a dynamic force assay to characterize frictional forces that impede sound-evoked vibrations of hair-cell bundles, the mechanosensory antennas of the inner ear. We find that opening and closing of mechanosensitive ion channels in the hair bundle produce frictional forces that can dominate viscous drag on the hair-bundle structure. We show that channel friction can be understood quantitatively using a physical theory of hair-bundle mechanics that includes channel kinetics. Friction originating from gating of ion channels is a concept that is relevant to all mechanosensitive channels. In the context of hearing, this channel friction may contribute to setting the characteristic frequency of the hair cell. Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force–displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell’s characteristic frequency of responsiveness.

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