A Virtual Hair Cell, II: Evaluation of Mechanoelectric Transduction Parameters

AbstractOur senses of hearing and balance rely on the extraordinarily sensitive molecular machinery of the inner ear to convert deflections as small as the width of a single carbon atom1,2 into electrical signals that the brain can process3. In humans and other vertebrates, transduction is mediated by hair cells4, where tension on tip links conveys force to mechanosensitive ion channels5. Each tip link comprises two helical filaments of atypical cadherins bound at their N-termini through two unique adhesion bonds6–8. Tip links must be strong enough to maintain a connection to the mechanotransduction channel under the dynamic forces exerted by sound or head movement—yet might also act as mechanical circuit breakers, releasing under extreme conditions to preserve the delicate structures within the hair cell. Previous studies have argued that this connection is exceptionally static, disrupted only by harsh chemical conditions or loud sound9–12. However, no direct mechanical measurements of the full tip-link connection have been performed. Here we describe the dynamics of the tip-link connection at single-molecule resolution and show how avidity conferred by its double stranded architecture enhances mechanical strength and lifetime, yet still enables it to act as a dynamic mechanical circuit breaker. We also show how the dynamic strength of the connection is facilitated by strong cis-dimerization and tuned by extracellular Ca2+, and we describe the unexpected etiology of a hereditary human deafness mutation. Remarkably, the connection is several thousand times more dynamic than previously thought, challenging current assumptions about tip-link stability and turnover rate, and providing insight into how the mechanotransduction apparatus conveys mechanical information. Our results reveal fundamental mechanisms that underlie mechanoelectric transduction in the inner ear, and provide a foundation for studying multi-component linkages in other biological systems.

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Mechanisms of hair cell mechanoelectric transduction: an update

Current Opinion in Otolaryngology & Head & Neck Surgery ◽

10.1097/00020840-200210000-00014 ◽

2002 ◽

Vol 10 (5) ◽

pp. 403-406

Author(s):

Ana E. Vázquez ◽

Ebenezer N. Yamoah

Keyword(s):

Hair Cell ◽

Mechanoelectric Transduction

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Differences Between Stereocilia Numbers on Type I and Type II Vestibular Hair Cells

Journal of Neurophysiology ◽

10.1152/jn.00428.2004 ◽

2004 ◽

Vol 92 (5) ◽

pp. 3153-3160 ◽

Cited By ~ 27

Author(s):

W. J. Moravec ◽

E. H. Peterson

Keyword(s):

Hair Cell ◽

Hair Cells ◽

Direct Evidence ◽

Cell Types ◽

Type I ◽

Type Ii ◽

Functional Roles ◽

Vestibular Hair Cells ◽

Mechanoelectric Transduction ◽

Bundle Structure

A major outstanding goal of vestibular neuroscience is to understand the distinctive functional roles of type I and type II hair cells. One important question is whether these two hair cell types differ in bundle structure. To address this, we have developed methods to characterize stereocilia numbers on identified type I and type II hair cells in the utricle of a turtle, Trachemys scripta. Our data indicate that type I hair cells, which occur only in the striola, average 95.9 ±16.73 (SD) stereocilia per bundle. In contrast, striolar type II hair cells have 59.9 ± 8.98 stereocilia, and type II hair cells in the adjacent extrastriola average 44.8 ± 10.82 stereocilia. Thus type I hair cells have the highest stereocilia counts in the utricle. These results provide the first direct evidence that type I hair cells have significantly more stereocilia than type II hair cells, and they suggest that the two hair cell types may differ in bundle mechanics and peak mechanoelectric transduction currents.

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Histological evaluation of cochlear hair cell damage from noise-induced hearing loss in chinchillas

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159217 ◽

1990 ◽

Vol 48 (3) ◽

pp. 332-333

Author(s):

R.V. Harrison ◽

R.J. Mount ◽

P. White ◽

N. Fukushima

Keyword(s):

Hair Cell ◽

Evoked Potential ◽

Cell Damage ◽

Acoustic Trauma ◽

Histological Evaluation ◽

Cell Integrity ◽

Functional Changes ◽

Cochlear Hair Cell ◽

Left And Right ◽

Contralateral Ear

In studies which attempt to define the influence of various factors on recovery of hair cell integrity after acoustic trauma, an experimental and a control ear which initially have equal degrees of damage are required. With in a group of animals receiving an identical level of acoustic trauma there is more symmetry between the ears of each individual, in respect to function, than between animals. Figure 1 illustrates this, left and right cochlear evoked potential (CAP) audiograms are shown for two chinchillas receiving identical trauma. For this reason the contralateral ear is used as control.To compliment such functional evaluations we have devised a scoring system, based on the condition of hair cell stereocilia as revealed by scanning electron microscopy, which permits total stereociliar damage to be expressed numerically. This quantification permits correlation of the degree of structural pathology with functional changes. In this paper wereport experiments to verify the symmetry of stereociliar integrity between two ears, both for normal (non-exposed) animals and chinchillas in which each ear has received identical noise trauma.

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The Organization of Actin Filaments in the Stereocilia of the Bird Cochlea

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002452 ◽

1980 ◽

Vol 38 ◽

pp. 554-555

Author(s):

E.J. Battles ◽

D. DeRosier ◽

J.C. Saunders ◽

L.G. Tilney

Keyword(s):

Hair Cell ◽

Diffraction Pattern ◽

Sea Urchin ◽

Actin Filaments ◽

Optical Diffraction ◽

Dense Material ◽

Apical Surface ◽

Structural Rigidity ◽

High Degree ◽

Degree Of Order

Extending from the apical surface of each hair cell of the chick cochlea are from 75 to 200 microvilli or stereocllia and one true cllium, the kinocilium. The stereocllia are arranged in rows of progressively increasing length (Fig. 1). Within each tapering sterocilium is a bundle of actin filaments with over 900 filaments near the tip yet only approximately 25 at the base where filaments are enmeshed in a dense material (Fig. 1); from here some of the filaments enter the apical surface of the cell (cuticular plate) as a rootlet. Examination of longitudinal sections of the stereocilia (Fig. 2) show that the filaments are aligned parallel to each other and show considerable order. Examination of an optical diffraction pattern of this bundle (Fig. 4) reveal that the actin filaments are packed such that the crossover points of adjacent actin filaments are inregister. A prominent reflection at 125Å−1 demonstrates that the filaments are cjossbridged by a macromolecular bridge situated at an average of 125Å−1 intervals (Fig. 4) in transverse sections the filaments appear hexagonally packed although there are regions where the filaments are less ordered (Fig. 3). In images processed in the computer to remove, noise and enhance detail periodic nature of the bridge can be clearly seen (see arrows Fig. 5). This image resembles that of an actin paracrystal formed from sea urchin extract composed of bundles of actin filaments crossbridged by a second protein. Thus the actin filaments in the bird stereocilia by being cross-bridged and packed with a high degree of order and produces a structure with considerable structural rigidity. Embryos were studied at various stages in development in an attempt to determine how the stereocilia form and how does the actin packing develops. These stages will be discussed.

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