Mechanical amplification by hair cells in the semicircular canals

Hair cells in the auditory, vestibular, and lateral-line systems of vertebrates receive inputs through a remarkable variety of accessory structures that impose complex mechanical loads on the mechanoreceptive hair bundles. Although the physiological and morphological properties of the hair bundles in each organ are specialized for detecting the relevant inputs, we propose that the mechanical load on the bundles also adjusts their responsiveness to external signals. We use a parsimonious description of active hair-bundle motility to show how the mechanical environment can regulate a bundle's innate behavior and response to input. We find that an unloaded hair bundle can behave very differently from one subjected to a mechanical load. Depending on how it is loaded, a hair bundle can function as a switch, active oscillator, quiescent resonator, or low-pass filter. Moreover, a bundle displays a sharply tuned, nonlinear, and sensitive response for some loading conditions and an untuned or weakly tuned, linear, and insensitive response under other circumstances. Our simple characterization of active hair-bundle motility explains qualitatively most of the observed features of bundle motion from different organs and organisms. The predictions stemming from this description provide insight into the operation of hair bundles in a variety of contexts.auditory system | hair cell | Hopf bifurcation | transduction | vestibular system A s the mechanosensitive organelle of a hair cell, the hair bundle detects acceleration in the vestibular system, sound in the auditory system, and fluid flow in the lateral-line system. Stimulation of any of these organs results in hair-bundle deflection and the consequent generation of an electrical signal by the hair cell (1). The hair bundle is more than a passive detector, however, for it can mechanically amplify an external input (2). Moreover, an active hair bundle can be tuned to specific frequencies, can oscillate spontaneously, and can exhibit a nonlinear response to external forcing. In contrast, a passive bundle is untuned, quiescent, and linear (2-6).The mechanical load imposed upon a hair bundle, which varies greatly depending on the receptor organ, might be expected to adjust the bundle's performance. In the mammalian cochlea, the hair bundles of outer hair cells are sensitive to the displacement of the overlying tectorial membrane to which they are attached. In contrast, the hair bundles of inner hair cells in the same organ are free of accessory structures but are deflected by fluid flow. Linear acceleration is detected in the utricle and saccule by hair bundles loaded with calcareous aggregates, the otoconia, embedded in an otolithic membrane. These hair bundles are deflected by the inertial force owing to the mass of the otoconia. The semicircular canals, the sensory organs for angular acceleration, contain groups of hair bundles encased in a gelatinous cupula. Head rotation induces within the canals a fluid flow that the bundles detect. The organization of hair bundles in late...

Section: Discussionmentioning

confidence: 97%

The diverse effects of mechanical loading on active hair bundles

Maoiléidigh

Nicola

Hudspeth

2012

“…Beyond cochlear mechanics, our findings have important implications for all sensory systems, which (with the exception of a few species of lizards) all contain accessory gelatinous structures overlying hair cells. Gels, such as the cupulae and otolithic membranes found in the vestibular system and those covering electrosensory hair cells on the skin of aquatic vertebrates, play a key role in hair cell stimulation (58)(59)(60). Much like the TM, these gels are poised to undergo deformations in response to transduction currents.…”

Section: Resultsmentioning

confidence: 99%

Electrokinetic properties of the mammalian tectorial membrane

Ghaffari

Page

Farrahi

et al. 2013

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...

“…If this were also the case in hair cells, it is conceivable that the SO could change its dimensions and rigidity depending on variations in intracellular Ca 2+ concentration (with the latter regulated, in part, by the large subcuticular mitochondria), and thus influence hair bundle or cuticular plate movements, or tilting of the cell neck. Any of these actions could alter the sensitivity of the transduction apparatus, and thus, mechanotransduction (45). Rüsch and Thurm (46) showed that hair bundles at different sites on the sensory epithelium exhibit differences in amplitude and in the time course of deflection.…”

Section: Discussionmentioning

confidence: 99%

“…We used serial sections of chinchilla utricular macula for conventional TEM and for IVEM. Our TEM methods were described previously (45). We analyzed a total of 41 tomograms using research facilities at the National Center for Microscopy and Imaging Research.…”

Section: Methodsmentioning

confidence: 99%

Striated organelle, a cytoskeletal structure positioned to modulate hair-cell transduction

Vranceanu

Perkins

Terada

et al. 2012

The striated organelle (SO), a cytoskeletal structure located in the apical region of cochlear and vestibular hair cells, consists of alternating, cross-linked, thick and thin filamentous bundles. In the vestibular periphery, the SO is well developed in both type I and type II hair cells. We studied the 3D structure of the SO with intermediate-voltage electron microscopy and electron microscope tomography. We also used antibodies to α-2 spectrin, one protein component, to trace development of the SO in vestibular hair cells over the first postnatal week. In type I cells, the SO forms an inverted open-ended cone attached to the cell membrane along both its upper and lower circumferences and separated from the cuticular plate by a dense cluster of exceptionally large mitochondria. In addition to contacts with the membrane and adjacent mitochondria, the SO is connected both directly and indirectly, via microtubules, to some stereociliary rootlets. The overall architecture of the apical region in type I hair cells-a striated structure restricting a cluster of large mitochondria between its filaments, the cuticular plate, and plasma membrane-suggests that the SO might serve two functions: to maintain hair-cell shape and to alter transduction by changing the geometry and mechanical properties of hair bundles.actin | cytoskeleton | stereocilia | ultrastructure | sensory receptors H air-cell stereocilia are important for mechanotransduction. Much is known about their structure, their mechanical properties, and their geometric arrangement (1-3). These cells are embedded in the cuticular plate, a dense structure composed of an actin gel (4) located at the apical end of the hair cell, which is thought to act as a rigid platform, helping stereocilia return to their resting positions after stimulus-evoked displacements (5, 6). What has never been investigated is how the cuticular plate might be stabilized by structures underneath it. Do these structures provide a foundation for the cuticular plate and the hair bundle?One such structure is the striated organelle (SO), also known as a laminated (or Friedman's) body, which is a cytoskeletal lattice underlying the apicolateral hair-cell membrane and consisting of alternating thick and thin filament bundles. When first described in vestibular hair cells in the 1960s, this structure was thought to be a pathological feature (7,8). It was later found to be a normal component of mammalian vestibular and cochlear inner, but not outer, hair cells (9-11). A striated structure, similar in position but differing in morphological details, has been described in other vertebrates (12)(13)(14).Slepecky et al. provided a description of the SO (10, 15, 16), including the periodicity of its filaments, their radial direction, attachment to the plasma membrane, and association with microtubules. Previous studies, even those based on conventional transmission electron microscopy (TEM) and deep-etch freeze fracture (9,10,15,17,18), did not provide a picture of the 3D structure of the organelle. Elec...