Review
A Bundle of Mechanisms: Inner-Ear Hair-Cell Mechanotransduction

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Highlights

MGCs, located at the tops of the sensory hair bundles, translate sound as well as the head’s orientation and acceleration into electrical signals.

Mechanical loading of a hair bundle by an accessory structure shapes the response of the bundle to stimulation. Bundles can be freestanding, encased in a cupula, or embedded in a sallet, tectorial membrane, or otolithic membrane.

Hair-bundle compliance and coordination between stereocilia control the macroscopic hair-cell response.

Owing to the sizable gating swing, channel gating affects hair-bundle compliance, creating mechanical nonlinearity.

Adaptation modulates the gating of the MGCs by means of calcium-dependent and independent processes.

Channel gating, adaptation, hair-bundle mechanics, and hair-bundle load determine force transfer to the MGCs, specializing a bundle’s response to distinct types of stimuli.

In the inner ear, the deflection of hair bundles, the sensory organelles of hair cells, activates mechanically-gated channels (MGCs). Hair bundles monitor orientation of the head, its angular and linear acceleration, and detect sound. Force applied to MGCs is shaped by intrinsic hair-bundle properties, by the mechanical load on the bundle, and by the filter imparted by the environment of the hair bundle. Channel gating and adaptation, the ability of the bundle to reset its operating point, contribute to hair-bundle mechanics. Recent data from mammalian hair cells challenge longstanding hypotheses regarding adaptation mechanisms and hair-bundle coherence. Variations between hair bundles from different organs in hair-bundle mechanics, mechanical load, channel gating, and adaptation may allow a hair bundle to selectively respond to specific sensory stimuli.

Section snippets

Inner-Ear Mechanosensation

Mechanosensation is one of the oldest sensory modalities, with functions spanning single-cell volume regulation, proprioception, organismal self-localization, and hearing 1, 2, 3, 4, 5. In particular, the vertebrate inner ear houses end organs specialized for sensing motion and sound. Vestibular systems primarily detect nonperiodic signals, arising from head orientation and acceleration, although their sensory hair cells also respond to low-frequency stimuli. In auditory systems, hair cells

The Macroscopic Environment

The environment of sensory hair bundles shapes the signals translated to the MGCs and determines which mechanical cue is best monitored by a particular system (Figure 1). In some hearing organs, hair bundles are freestanding; stimulated and coupled by fluid forces, which intensify with the stimulus frequency. To coordinate their motion in other settings, bundles are embedded in a cupula, tectorial structure, otolithic membrane, or sallet. The mechanical structure of the organ dictates the

Gating-Spring Theory

Because many animals hear high-frequency sounds (>1 kHz), their MGCs must respond quickly to stimulation (<1 ms), implicating direct mechanical coupling between bundle motion and channel gating. The speed of channel gating is set by the channel properties and the mechanical components transmitting force on the bundle to force at the channel.

The opening of the MGCs is concomitant with the extension of an elastic element, known as the gating spring, in series with the channel [22]. Channel opening

Adaptation

Hair-bundle mechanosensitivity is also shaped by an additional dynamic process, termed adaptation, which shifts the operating point of a hair bundle in response to a step stimulus without loss of sensitivity at the new resting position (Figure 4) 44, 45, 46. Adaptation can be envisioned as a change in the force sensed by MGCs that modulates their probability of opening. This process extends the dynamic range of a hair bundle, provides high-pass filtering properties to the hair bundle, and is

Active Signal Detection

Signal detection by hair bundles is limited by intrinsic stochastic fluctuations setting the thresholds of all auditory and vestibular systems [69]. These fluctuations are inherently related to damping [70], which slows responses to stimuli. To encode temporal aspects of a stimulus, hair bundles must respond with sufficient speed and amplitude to elicit a neural response and distinguish external signals from intrinsic noise. Because of these fundamental limits, it is likely that both auditory

Concluding Remarks and Future Perspectives

Although it is clear that the function of auditory and vestibular organs is dictated by the environment and properties of their mechanosensory hair bundles, fundamental questions remain (see Outstanding Questions). Faster and more precise techniques are needed to stimulate mammalian hair bundles [96]. Modeling predicts that a stimulus that better reproduces the natural in vivo input to a hair bundle will lead to faster adaptation time constants and narrower activation curves [20]. Ascertaining

Acknowledgments

This work was supported by NIDCD grants DC003896 and DC014658.

Glossary

Amplification
in the context of inner-ear research, refers to a boost in the mechanical response of the living inner ear to stimulation in comparison to immediately post-mortem.
Activation curve
the MET current as a function of hair bundle displacement.
Bifurcation
a change in the qualitative behavior of a system owing to an alteration in operating point. At a fold bifurcation, a system develops two additional steady states. At a Hopf bifurcation, a system transitions from quiescence to

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