A model for amplification of hair-bundle motion by cyclical binding of Ca 2+ to mechanoelectrical-transduction channels

The tectorial membrane (TM) clearly plays a mechanical role in stimulating cochlear sensory receptors, but the presence of fixed charge in TM constituents suggests that electromechanical properties also may be important. Here, we measure the fixed charge density of the TM and show that this density of fixed charge is sufficient to affect mechanical properties and to generate electrokinetic motions. In particular, alternating currents applied to the middle and marginal zones of isolated TM segments evoke motions at audio frequencies (1-1,000 Hz). Electrically evoked motions are nanometer scaled (∼5-900 nm), decrease with increasing stimulus frequency, and scale linearly over a broad range of electric field amplitudes (0.05-20 kV/m). These findings show that the mammalian TM is highly charged and suggest the importance of a unique TM electrokinetic mechanism.cochlear amplification | cochlear mechanics | mechanoelectrical transduction | motility T he mammalian cochlea is a remarkable sensor capable of detecting and analyzing sounds that generate subatomic vibrations (1). This extraordinary sensing property depends on mechanoelectrical transduction (MET) of cochlear hair cells (2, 3), which are functionally classified as inner and outer hair cells (OHCs). Both types of hair cells project stereociliary hair bundles from their apical surface toward an overlying extracellular matrix called the tectorial membrane (TM). Because of its strategic position above the hair bundles, the TM is believed to play a critical role in bundle deflection. Recently, genetic studies confirmed the importance of the TM in hair cell stimulation by highlighting how mutations of TM proteins cause severe hearing deficits, even when the TM and its structural attachments appear to be normal under electron microscopy (4-8).Despite significant evidence establishing the importance of the TM in normal cochlear function, relatively little is known about the TM's basic physicochemical properties and mechanistic role. Historically, models of cochlear function have represented the TM as a stiff lever with a compliant hinge, as a resonant mass-spring system, or as an inertial body (9-16). However, these models exclude important phenomena, such as longitudinal coupling (17)(18)(19)(20), and assume that only mechanical properties of the TM are important. It now is clear that the TM is a biphasic poroelastic tissue (21), which manifests longitudinal coupling in the form of traveling waves (18)(19)(20).Furthermore, TM macromolecules comprise not only mechanical constituents (21-26) such as collagen fibrils, but also charged constituents such as glycosaminoglycans (GAGs), which might affect mechanical properties (Fig. 1) (27-35). GAGs in the TM carry sulfate (SO 3 − ) and carboxyl (COO − ) charge groups, which are fully ionized at physiological pH and neutralized at acidic pH values (pKs between 2 and 4) (27). In contrast, the net charge on TM collagen constituents is small at physiological pH because the net charge of amino (NH 3 + ) and carboxyl groups is z...

Section: Resultssupporting

confidence: 55%

Electrokinetic properties of the mammalian tectorial membrane

Ghaffari

Page

Farrahi

et al. 2013

“…Similar systems that involve the concerted movements of clustered myosin molecules are known to be subject to a Hopf bifurcation (25). Ca 2ϩ -driven reclosure of transduction channels (14,26), a mechanism that can operate at relatively high frequencies, has also been shown by modeling to experience a Hopf bifurcation (27).…”

Section: Scaling Of Responses With Stimulationmentioning

confidence: 99%

Compressive nonlinearity in the hair bundle's active response to mechanical stimulation

Martin

Hudspeth

2001

Self Cite

174

133

The auditory system's ability to interpret sounds over a wide range of amplitudes rests on the nonlinear responsiveness of the ear. Whether measured by basilar-membrane vibration, nerve-fiber activity, or perceived loudness, the ear is most sensitive to small signals and grows progressively less responsive as stimulation becomes stronger. Seeking a correlate of this behavior at the level of mechanoelectrical transduction, we examined the responses of hair bundles to direct mechanical stimulation. As reported by the motion of an attached glass fiber, an active hair bundle from the bullfrog's sacculus oscillates spontaneously. Sinusoidal movement of the fiber's base by as little as ؎1 nm, corresponding to the application at the bundle's top of a force of ؎0.3 pN, causes detectable phase-locking of the bundle's oscillations to the stimulus. Although entrainment increases as the stimulus grows, the amplitude of the hair-bundle movement does not rise until phaselocking is nearly complete. A bundle is most sensitive to stimulation at its frequency of spontaneous oscillation. Far from that frequency, the sensitivity of an active hair bundle resembles that of a passive bundle. Over most of its range, an active hair bundle's response grows as the one-third power of the stimulus amplitude; the bundle's sensitivity declines accordingly in proportion to the negative two-thirds power of the excitation. This scaling behavior, also found in the response of the mammalian basilar membrane to sound, signals the operation of an amplificatory process at the brink of an oscillatory instability, a Hopf bifurcation.H earing operates over a remarkably broad dynamic range.The faintest sounds we can sense impart to the ear an amount of energy per cycle of oscillation comparable to thermal energy (1). At the other extreme, the ear endures urban, industrial, and military noise that represents sound pressures 6 orders of magnitude greater than threshold! To accommodate such diverse stimuli, the ear's responsiveness must be nonlinear. The common use of decibels, a logarithmic metric, for the intensity of sound reflects this fact. Nonlinear compression of responsiveness is evident throughout the ear's transduction process. The perceived loudness, the firing rate of auditory-nerve axons, and the basilar-membrane vibration in the cochlea all grow more gradually than the input signal. In the chinchilla's cochlea, for example, sound-pressure levels ranging over 120 dB are represented as basilar-membrane vibrations spanning but 2 orders of magnitude (ref. 2; reviewed in ref.3). The basilar membrane's responsiveness, defined as the increase in amplitude of vibration evoked by an increment in soundpressure level, is greatest for threshold stimuli and then declines progressively at moderate to intense levels.The nonlinearity of aural responsiveness is associated closely with the ear's great sensitivity, sharp frequency selectivity, and ability to generate otoacoustic emissions. These four characteristics of hearing result from an active process that ...

“…As the channels close, the tension in each associated gating spring increases, pulling the hair bundle in the negative direction. This process underlies active hair-bundle motility that can both foster spontaneous bundle oscillation and amplify mechanical inputs (33,46). Ca 2ϩ affects all three of the proposed components of active hair-bundle motility in ways that have been incorporated into the model (P. Martin, D.B., Y. Choe, and A.J.H., unpublished data).…”

Section: Duality Of Force-producing Mechanismsmentioning

confidence: 99%

Hair-bundle movements elicited by transepithelial electrical stimulation of hair cells in the sacculus of the bullfrog

Bozovic

Hudspeth

2003

Self Cite

Electrically evoked otoacoustic emission is a manifestation of reverse transduction by the inner ear. We present evidence for a single-cell correlate of this phenomenon, hair-bundle movement driven by transepithelial electrical stimulation of the frog's sacculus. Responses could be observed at stimulus frequencies up to 1 kHz, an order of magnitude higher than the organ's natural range of sensitivity to acceleration or sound. Measurements at highstimulus frequencies and pharmacological treatments allow us to distinguish two mechanisms that mediate the electrical responses: myosin-based adaptation and Ca 2؉ -dependent reclosure of transduction channels. These mechanisms also participate in the active process that amplifies and tunes the mechanical responses of this receptor organ. Transient application of the channel blocker gentamicin demonstrated the crucial role of mechanoelectrical transduction channels in the rapid responses to electrical stimulation. A model for electrically driven bundle motion that incorporates the negative stiffness of the hair bundle as well as its two mechanisms of motility captures the essential features of the measured responses.