The sensory and motor roles of auditory hair cells

The vertebrate inner ear possesses an active process that provides nonlinear amplification of mechanical stimuli. A candidate for this process is active hair bundle mechanics observed, for instance, for hair cells of the bullfrog's sacculus. Hair bundles in various inner ear organs are coupled by overlying membranes. Using a stochastic description of active hair bundle dynamics, we study the consequences of an elastic coupling on the properties of amplification. We report that collective effects in arrays of hair bundles can enhance the amplification gain and the sharpness of frequency tuning as compared with the performance of an isolated hair bundle. We also discuss the transient response elicited by the sudden onset of a periodic stimulus and its relation to temporal integration curves. Simulations of systems with a gradient of intrinsic frequencies show an enhanced amplification gain while preserving a frequency gradient, provided the coupling strength is similar to the hair bundle stiffness. We relate our findings to the situation in the bullfrog's sacculus and the mammalian cochlea.auditory amplifier ͉ hair cells ͉ nonlinear oscillators ͉ stochastic processes T he extraordinary ability of the vertebrate ear to detect sound stimuli over many orders of magnitude in sound amplitude relies on active processes. The key features of the auditory amplifier are (i) the amplification of weak stimuli, (ii) a compressive nonlinearity for stronger stimuli, (iii) frequency selectivity, and (iv) the generation of spontaneous emissions (1-3). All these properties could be understood as the consequence of nonlinear dynamic oscillators that operate in the ear (4-7).

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confidence: 99%

“…First, outer hair cell electromotility, which involves cell body contractions (9), could be an important element of the amplifier in the mammalian cochlea (10)(11)(12). Second, the hair bundle, which is the mechanosensitive organelle at the apical surface of the hair cell, could generate forces and movements that contribute to amplification (13)(14)(15).…”

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confidence: 99%

Enhancement of sensitivity gain and frequency tuning by coupling of active hair bundles

Dierkes

Lindner

Jülicher

2008

“…In particular, the hair cell can power active movements of its hair bundle, including spontaneous oscillations (8,9). Nevertheless, the performance of the hair bundle, both as transducer and amplifier, are influenced by friction for two reasons.…”

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confidence: 99%

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

Bormuth

Barral

Joanny

et al. 2014

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.mechanosensitive channels | protein friction | hair-bundle mechanosensitivity | cell mechanics | auditory system S ound evokes vibrations in the inner ear that are detected by sensory hair cells. Mechanosensitivity stems from mechanical activation of ion channels by tension changes in tip links that interconnect neighboring stereocilia of the hair-cell bundle (1). The acute sensitivity and sharp frequency selectivity of auditory detection rely on efficient transmission of the energy derived from the acoustic stimulus to the apparatus that mediates mechanoelectrical transduction. However, at least three sources of friction threaten to dissipate the energy of the vibrating hair bundle. First, viscous drag by the surrounding fluid provides a minimum source of damping (2, 3). Second, viscoelasticity of the tip links, or of proteins in series with these links, may result in additional dissipation during hair-bundle deflections (4). Third, an intrinsic source of friction-called "channel friction" in the following-is related to thermal fluctuations of the transduction channels between their open and closed states (5). The fluctuation-dissipation theorem dictates that this source of mechanical noise be related to friction forces on the hair bundle.To circumvent the fundamental challenge posed by friction, hair cells mobilize internal ...

“…Inner hair cells transduce mechanical vibrations into electrical signals that are eventually transmitted to the brain to be transformed into hearing signals (1), whereas outer hair cells (OHCs) (2) amplify the vibrations of the basilar membrane (3). Mechanical stimuli that are detected as excitatory deflect a hair bundle, thus increasing tension in the tip link, a filament stretched between the tops of stereocilia.…”

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confidence: 99%

A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness

Ficarella

Leva²,

Bortolozzi

et al. 2007

113

Ca 2؉ enters the stereocilia of hair cells through mechanoelectrical transduction channels opened by the deflection of the hair bundle and is exported back to endolymph by an unusual splicing isoform (w/a) of plasma-membrane calcium-pump isoform 2 (PMCA2). Ablation or missense mutations of the pump cause deafness, as described for the G283S mutation in the deafwaddler (dfw) mouse. A deafness-inducing missense mutation of PMCA2 (G293S) has been identified in a human family. The family also was screened for mutations in cadherin 23, which accentuated hearing loss in a previously described human family with a PMCA2 mutation. A T1999S substitution was detected in the cadherin 23 gene of the healthy father and affected son but not in that of the unaffected mother, who presented instead the PMCA2 mutation. The w/a isoform was overexpressed in CHO cells. At variance with the other PMCA2 isoforms, it became activated only marginally when exposed to a Ca 2؉ pulse. The G293S and G283S mutations delayed the dissipation of Ca 2؉ transients induced in CHO cells by InsP3. In organotypic cultures, Ca 2؉ imaging of vestibular hair cells showed that the dissipation of stereociliary Ca 2؉ transients induced by Ca 2؉ uncaging was compromised in the dfw and PMCA2 knockout mice, as was the sensitivity of the mechanoelectrical transduction channels to hair bundle displacement in cochlear hair cells.hereditary hearing loss ͉ mutations ͉ calcium homeostasis ͉ calcium transport T he receptive organelle of sensory hair cells in the mammalian cochlea, the stereocilia bundle, protrudes from the cell's apical surface. Inner hair cells transduce mechanical vibrations into electrical signals that are eventually transmitted to the brain to be transformed into hearing signals (1), whereas outer hair cells (OHCs) (2) amplify the vibrations of the basilar membrane (3). Mechanical stimuli that are detected as excitatory deflect a hair bundle, thus increasing tension in the tip link, a filament stretched between the tops of stereocilia. This tension is conveyed to mechanosensitive transduction (MET) channels that open to allow ions into the cell (4). The apical surface of hair cells is bathed in endolymph, which is rich in K ϩ but low in Na ϩ and Ca 2ϩ (5). K ϩ carries most the transduction current, but MET channels are Ca 2ϩ selective, i.e., Ca 2ϩ influx is significant even at the low Ca 2ϩ levels of the endolymph, which are much lower than those of other extracellular fluids (6-10): 20-23 M in the rodent cochlea (11, 12), 200-250 M in the vestibular system, possibly because of the presence there of calcium carbonate crystals (13,14). Approximately 10% of the MET current may actually be carried by Ca 2ϩ ions (15). Ca 2ϩ entering through MET channels is rapidly sequestered by buffers in the stereocilia (16,17) and is shuttled back to endolymph by the plasma membrane Ca 2ϩ pump (PMCA) (18,19), which is very concentrated in the stereocilia membrane (Ϸ2,000 per squared micrometer) (15, 19-21). The PMCA is assumed to increase Ca 2ϩ in the immediate pro...