Decades-old model of slow adaptation in sensory hair cells is not supported in mammals

Abstract

Hair cells detect sound and motion through a mechano-electric transduction (MET) process mediated by tip links connecting shorter stereocilia to adjacent taller stereocilia. Adaptation is a key feature of MET that regulates a cell’s dynamic range and frequency selectivity. A decades-old hypothesis proposes that slow adaptation requires myosin motors to modulate the tip-link position on taller stereocilia. This “motor model” depended on data suggesting that the receptor current decay had a time course similar to that of hair-bundle creep (a continued movement in the direction of a step-like force stimulus). Using cochlear and vestibular hair cells of mice, rats, and gerbils, we assessed how modulating adaptation affected hair-bundle creep. Our results are consistent with slow adaptation requiring myosin motors. However, the hair-bundle creep and slow adaptation were uncorrelated, challenging a critical piece of evidence upholding the motor model. Considering these data, we propose a revised model of hair cell adaptation.

Fluid Jet Stimulation of Auditory Hair Bundles Reveal Spatial Non-uniformities and Two Viscoelastic-Like Mechanisms

“…For experiments without the hair bundle, the fluid jet and flexible fiber were moved ∼200 µm above the epithelium. (Caprara et al, 2020). Using the new analysis method to characterize the motion of the whole hair bundle, we also observed that the spatial non-uniformity was decreased after BAPTA treatment (Figure 4E), indicating that the BAPTAsensitive links had a contribution to the spatial non-uniformity, consistent with the modeling data.…”

“…The bundle displacement shows an initial motion due to the stimulus force onset, followed by a mechanical creep defined as a continued motion in the direction of the stimulus. The mechanical creep was characterized by a fast and slow exponential process and was not due to the motion of the apical surface (Caprara et al, 2019) and is diminished by fixing the tissue (Caprara et al, 2020). BAPTA treatment increased the overall motion and altered the creep kinetics but did not eliminate it (Caprara et al, 2020), suggesting that channel gating or tip-link stretch do not solely underlie the creep but may contribute to it.…”

“…The mechanical creep was characterized by a fast and slow exponential process and was not due to the motion of the apical surface (Caprara et al, 2019) and is diminished by fixing the tissue (Caprara et al, 2020). BAPTA treatment increased the overall motion and altered the creep kinetics but did not eliminate it (Caprara et al, 2020), suggesting that channel gating or tip-link stretch do not solely underlie the creep but may contribute to it. This result was consistent with Tobin et al (2019), where the creep was not abolished after BAPTA treatment for the 2 and 4 kHz locations.…”

Functional Role of Class III Myosins in Hair Cells

“…Indeed, MYO1C was found to be crucial in MET channel adaptation, a process by which the MET channel gating is reset between stimuli ( Holt et al, 2002 ). The adaptation process was originally thought to be regulated via MYO1C alone, though further research has suggested other myosin motors may play a role ( Caprara et al, 2020 ).…”

“…However, its slow ensemble and single molecule motility (16 and 11 nm/s, respectively) suggest it may not be well suiting for long range transport ( Inoue and Ikebe, 2003 ; Sato et al, 2017 ). Two recent studies which studied the role of myosin motors in the MET channel adaptation reported that MYO7A is a good candidate to maintain resting tension on the MET channel, but its slow motility speed likely precludes it from functioning in adaptation ( Caprara et al, 2020 ; Li et al, 2020 ). Thus, future studies are crucial for specifically examining the role of MYO7A in maintaining tip-link tension and MET channel gating.…”