DOCSLIB.ORG

Tip-Link Integrity and Mechanical Transduction in Vertebrate Hair Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tip-Link Integrity and Mechanical Transduction in Vertebrate Hair Cells Neuron, Vol. 7, 985-994, December, 1991, Copyright 0 1991 by Cell Press Tip-link Integrity and Mechanical Transduction in Vertebrate Hair Cells John A. Assad,*+ Gordon M. G. Shepherd,* This suggests that the gating springs are not rigid ele- and David P. Corey*511 ments, but can be slack-that they can pull but not *Department of Neurobiology push on the channels (Corey and Hudspeth, 1983). *Program in Neuroscience The structural correlate of this process has not been Harvard Medical School well established. A simple model has evolved from Boston, Massachusetts 02115 several independent observations. First, measure- SDepartment of Neurology ment of current flow near moving bundles indicated Massachusetts General Hospital thatthetransductionchannelsareatornearthetipsof Boston, Massachusetts 02114 the stereocilia (Hudspeth, 1982). While this has been IINeuroscience Group challenged by measurements with a Ca*+ indicator Howard Hughes Medical Institute dye (Ohmori, 1988), two additional experirnents have corroborated the localization of the channels at the tips (Huang and Corey, 1990, Biophys. Sot., abstract; Summary Jaramillo and Hudspeth, 1991). Second, the discovery of fine filaments between the tips of adjacent ster- An attractive hypothesis for hair-cell transduction is that eocilia led to the suggestion that these “tip links”were fine, filamentous “tip links” pull directly on mechani- the actual mechanical linkages to the channels (Pick- cally sensitive ion channels located at the tips of the les et al., 1984). The geometry of the bundle is such stereocilia. We tested the involvement of tip links in the that excitatory displacements would stretch the tip transduction process by treating bundles with a BAPTA- links and apply tension to the channels; inhibitory buffered, low-Ca*+ saline (1O-v M). BAPTA abolished the displacements would relax them. All vertebrate hair transduction current in a few hundred milliseconds. cells so far examined-from different species and dif- BAPTA treatment for a few seconds eliminated the tip ferent organs whose stereociliary morphology may links observed by either scanning or transmission elec- otherwise vary-possess tip links. The tip-lr,nk hypoth- tron microscopy. BAPTA also eliminated the voltage- esis for transduction is thus extremely attractive, yet dependent movement and caused a positive bundle dis- direct evidence for it is limited. placement of 133 nm, in quantitative agreement with a In this paper we directly implicate the tip links in model for regulation of tension. We conclude that tip the transduction process, with the finding that a brief links convey tension to the transduction channels of hair treatment of low extracellular Ca2+ destroys both the cells. tip links and the mechanical sensitivity. In dissociated cells, moreover, low Ca*+ both abolishes the voltage- Introduction dependent bundle movement driven by the cells’ active regulation of gating spring tension and causes When the mechanosensitive bundle of a vertebrate the bundle to relax forward by 133 nm, 1ir-rquantita- hair cell is displaced in the positive direction (toward tive agreement with the idea that low Ca2+ destroys the taller stereocilia), transduction channels open and transduction by cutting the attachments to the ion allow the flow of positive ions into the cell. The open- channels. ing of a channel is thought to result from an increase of mechanical tension on the channel protein itself. Results The principal evidence for direct mechanical gating of these channels is that the transduction process is Abolition of Transduction by low Ca*+ extremely rapid (Corey and Hudspeth, 1979a), that the It has long been recognized that Ca*+ in the solution opening and closing rates depend on the size of the bathingthe hair bundles is required for hair-cell trans- stimulus (Corey and Hudspeth, 1983; Crawford et al., duction (Sand, 1975; Corey and Hudspeth, 1979b; 1989), and that the mechanical complianceof a bundle Crawford et al., 1991). While earlier experiments sug- includes a component that matches the opening of gested that Ca*+ might carry the receptor current the channels (Howard and Hudspeth, 1988). In this (Sand, 1975), more recent work views Ca2+ as a neces- view, the open probability is a direct function of ten- sary cofactor for the transduction apparatus (Craw- sion, conveyed by an elastic “gating spring.” A pecu- ford et al., 1991). We have reexamined the Ca2+ depen- liarity of the gating kinetics is that channel opening is dence with whole-cell voltage clamp, direct bundle progressively speeded by larger positive displace- stimulation, and rapid application of tes,t solutions. ments, whereas the closing rate is independent of the Figure 1 shows transduction currents of single cells in stimulus for sufficiently large negative displacements. response to a triangle-wave stimulus of 1.0 pm peak- to-peak amplitude; this was a saturating stimulus for these cells. The bath contained a normal frog saline + Present address: Department of Physiology and Center for Vi- sual Science, University of Rochester, Rochester, New York with 4 mM Ca*+. Halfway through the record, a low- 14642. Ca*+ saline (lOmg M; buffered with 5 mM BAPTA) was Neur0n 986 I I I 1 Time (set) Figure 1. Abolition of Transduction by Low Ca’+ (A-C) Transduction current in 3 different cells elicited by a 1 pm peak-to-peak, tnangk-wave displacement ot the bundle (bottom trace) A 5 mM BAPTA solution was delivered by a pressure pipette positioned about 20 @m from the cell. at the time Indicated by the bar In all 3 cases, transduction current was abolished by the BAPTA treatment and did not return for the duration ot the recording, usually several minutes after the exposure to low Ca2+. Membrane potential was maintained at -80 mV by the patch clamp. The bath contained the external recording solution, with 4 mM Caz+. puffed onto the cell from a distance of about 20 pm. curve-which relates receptor current to displace- The bundlewas held firmly bythe stimulus probeand ments-toward more negative positions, so that more continued to be driven by the triangle-wave stimulus. channels are open at rest (Assad et al., 1989; Crawford As the wave of low Ca2+ reached the bundle, the trans- et al., 1989, 1991). In extreme cases, it is possible that duction currentwas initially increased by about lOO%, such a shift is so large that all the channels are open a consequence of relieving a voltage-dependent block with zerodisplacement and that a cell appears insensi- of the channels by Caz+ (Assad and Corey, unpub- tive to mechanical stimuli, while in fact a sufficiently lished data; Crawford et al., 1991). In as little as 50 ms, large negative displacement could close channels. however, the transduction currentwas abolished, and That does not appear to account for the loss of sensi- it was not restored even several minutes after the tivity in this experiment, because there was not evi- BAPTA solution diffused away. In Figures IA and IB dence of a progressive shift of the I(X) curve, because the total membrane current increased, at least tran- the stimulus included large negative excursions that siently, during the exposure to low Ca*+. This increase were ineffectual in closing channels, and because the is due, at least in part, to an observed shift in the effect was not reversible upon return to normal Ca*- activation of basolaterally situated voltage-dependent concentration. It seems more likely that some part of Ca2+ channels (Roberts et al., 1990) to more negative the transduction apparatus was actually broken by potentials- perhaps as a result of alleviation of screen- lowering the Ca*+ concentration. ing charge-coupled with an increased monovalent ion flux through these channels (Assad and Corey, Abolition of Tip links by low CaZ+ unpublished data; Hess et al., 1986). To determinewhat part of the transduction apparatus We and others have found that lowering the Ca2+ was broken, hair cells were similarly treated with low concentration inside the stereocilia shifts the I(X) Ca*+ and prepared for scanning electron microscopy Hair Cell Transduction 987 Control Figure 2. Scanning Electron Micrographs of Stereocilia Treated with CaZ+ or BAPTA Ca2+-treated sacculi (left) were dissected in a 0.1 mM Caz+ solution and then placed in 4 mM Ca*+ before fixation in 4 mM Caz+. BAPTA-treated sacculi (right) were dissected in the same way, but placed in a 5 mM BAPTA solution for 10 s before fixation in 4 mM Caz+. Bar, 500 nm. (SEM). Sacculi were dissected as for physiological ex- periments and treated to remove their otolithic mem- branes, but were not dissociated. Experimental sac- culi were transferred to a solution buffered with 5 mM BAPTA for about 10 s and then immediately returned to normal saline. Control sacculi were transferred to normal saline in the same manner. Both sets were fixed with glutaraldehyde and 0~0~ and processed for field emission SEM. In order to photograph a representative sample of both control and experimental bundles, maculae were viewed at low magnification (3000x) and bun- dles were chosen more or less randomly from all re- gions. At the low magnification it was not possible to observe tip links; thus, their presence could not bias the choice of a cell. Bundles were photographed at Figure 3. Intact Tip Links following Detergent Treatment high magnification (50,000x), from an angle approxi- Specimen was dissected in 0.1 mM CaI+ and then maintained in control saline containing 4 mM Ca2+ at all times prior to fixation. mately perpendicular to the bevel of the tips. Twelve Triton X-100 (2%) was added to the fixative for the final 20 min to20 bundles were photographed from each of 4 mac- of fixation. Bar, 500 nm. ulae. Figure 2 shows representative images of control (left) and BAPTA-treated (right) bundles taken with an accelerating voltage of 4 kV. The stereocilia in both ular, the bundles were not splayed or otherwise dis- samples appearwell preserved, with no bending.
Load more

Recommended publications
  • Pejvakin, a Candidate Stereociliary Rootlet Protein, Regulates Hair Cell Function in a Cell-Autonomous Manner
    The Journal of Neuroscience, March 29, 2017 • 37(13):3447–3464 • 3447 Neurobiology of Disease Pejvakin, a Candidate Stereociliary Rootlet Protein, Regulates Hair Cell Function in a Cell-Autonomous Manner X Marcin Kazmierczak,1* Piotr Kazmierczak,2* XAnthony W. Peng,3,4 Suzan L. Harris,1 Prahar Shah,1 Jean-Luc Puel,2 Marc Lenoir,2 XSantos J. Franco,5 and Martin Schwander1 1Department of Cell Biology and Neuroscience, Rutgers the State University of New Jersey, Piscataway, New Jersey 08854, 2Inserm U1051, Institute for Neurosciences of Montpellier, 34091, Montpellier cedex 5, France, 3Department of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, California 94305, 4Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, Colorado 80045, and 5Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado 80045 Mutations in the Pejvakin (PJVK) gene are thought to cause auditory neuropathy and hearing loss of cochlear origin by affecting noise-inducedperoxisomeproliferationinauditoryhaircellsandneurons.Herewedemonstratethatlossofpejvakininhaircells,butnot in neurons, causes profound hearing loss and outer hair cell degeneration in mice. Pejvakin binds to and colocalizes with the rootlet component TRIOBP at the base of stereocilia in injectoporated hair cells, a pattern that is disrupted by deafness-associated PJVK mutations. Hair cells of pejvakin-deficient mice develop normal rootlets, but hair bundle morphology and mechanotransduction are affected before the onset of hearing. Some mechanotransducing shorter row stereocilia are missing, whereas the remaining ones exhibit overextended tips and a greater variability in height and width. Unlike previous studies of Pjvk alleles with neuronal dysfunction, our findings reveal a cell-autonomous role of pejvakin in maintaining stereocilia architecture that is critical for hair cell function.
    [Show full text]
  • Molecular Characterization of Hair Cell Metabolism and Tip Link Damage
    Molecular characterization of hair cell metabolism and tip link damage by Kateri J. Spinelli A dissertation in partial fulfillment of the requirements for the degree of Doctor of Philosophy Presented to the Neuroscience Graduate Program Oregon Health & Science University School of Medicine February 2012 Table of Contents List of Figures ………………………………………………………………………………………………………..…… iv AcKnowledgments ……………………………………………………………………………………………………… vii Abstract ……………………………………………………………………………………………………………………… ix Chapter 1 – Introduction ............................................................................................. 1 Chapter 2 – Distinct energy metabolism of auditory and vestibular sensory epithelia revealed by quantitative mass spectrometry using MS2 intensities ........................... 13 Abstract ........................................................................................................................ 14 Introduction .................................................................................................................. 15 Results .......................................................................................................................... 17 Label-free quantitation with MS2 intensities ............................................... 17 Quantitation of proteins in chicK auditory and vestibular epithelia ............. 18 Verifying mass spectrometry quantitation ................................................... 21 Comparing protein and mRNA abundance ..................................................
    [Show full text]
  • The Other Senses
    COGS 17 Fall 2009 The Other Senses Mary ET Boyle, Ph.D. Department of Cognitive Science UCSD Peripheral Vestibular Structure: • Inner ear miniaturized accelerometers inertial guidance devices Continually reporting information about: motions and position of head and body Information goes to: brainstem cerebellum somatic sensory cortices 1 Central Vestibular Structure: • Vestibular Nuclei Directly controls motor neurons controlling: extraocular cervical postural Important for: stabilization of gaze head orientation posture during movements The Vestibular Labyrinth: • Main peripheral component Connected with cochlea Uses same specialized hair cells Transduce physical motion into neural impulses head movements inertial effects due to gravity ground-borne vibrations Vestibular endolymph (like cochlear endolymph) high in K+ and low in Na+ 2 Vestibular navigation • Translational movements are in terms of x, y, z Saccule Utricle Rotational movements roll, pitch, yaw • Roll – tumbling left or right -- move your head from your left to your right shoulder • Pitch – nod your head “yes” • Yaw – shake your head “no” Semicircular canals 3 The Vestibular Labyrinth – otolith organs • Two otolith organs - (vestibular sacs) Utricle – hair cells are located on the floor- horizontal plane Saccule – hair cells are located on the wall – vertical motion •Respond to: Information about the position of the head relative to the body utricle cochlea Vestibulocochlear nerve VIII saccule The Vestibular Labyrinth – semicircular canals • Three semicircular canals- (vestibular sacs) Oriented in three planes Ampullae – located at the base of each of the semicircular canals. •Respond to: Rotational accelerations of the head ampullae cochlea Vestibulocochlear nerve VIII 4 The Vestibular Hair cells Similar to auditory hair cells Mechanically gated transduction Channels located at the tips of the stereocilia Otolithic hair cells Scanning EM of calcium carbonate crystals (otoconia) in the utricular macula of the cat.
    [Show full text]
  • Stiffness and Tension Gradients of the Hair Cell's Tip-Link Complex In
    RESEARCH ARTICLE Stiffness and tension gradients of the hair cell’s tip-link complex in the mammalian cochlea Me´ lanie Tobin1,2, Atitheb Chaiyasitdhi1,2†, Vincent Michel2,3,4†, Nicolas Michalski2,3,4, Pascal Martin1,2* 1Laboratoire Physico-Chimie Curie, Institut Curie, PSL Research University, CNRS UMR168, Paris, France; 2Sorbonne Universite´, Paris, France; 3Laboratoire de Ge´ne´tique et Physiologie de l’Audition, Institut Pasteur, Paris, France; 4UMRS 1120, Institut National de la Sante´ et de la Recherche Me´dicale (INSERM), Paris, France Abstract Sound analysis by the cochlea relies on frequency tuning of mechanosensory hair cells along a tonotopic axis. To clarify the underlying biophysical mechanism, we have investigated the micromechanical properties of the hair cell’s mechanoreceptive hair bundle within the apical half of the rat cochlea. We studied both inner and outer hair cells, which send nervous signals to the brain and amplify cochlear vibrations, respectively. We find that tonotopy is associated with gradients of stiffness and resting mechanical tension, with steeper gradients for outer hair cells, emphasizing the division of labor between the two hair-cell types. We demonstrate that tension in the tip links that convey force to the mechano-electrical transduction channels increases at reduced Ca2+. Finally, we reveal gradients in stiffness and tension at the level of a single tip link. We conclude that mechanical gradients of the tip-link complex may help specify the characteristic frequency of the hair cell. DOI: https://doi.org/10.7554/eLife.43473.001 *For correspondence: [email protected] †These authors contributed equally to this work Introduction The cochlea—the auditory organ of the inner ear—is endowed with a few thousands of mechanosen- Competing interests: The sory hair cells that are each tuned to detect a characteristic sound frequency (Fettiplace and Kim, authors declare that no 2014).
    [Show full text]
  • Lipid Bilayer Mediates Ion-Channel Cooperativity in a Model of Hair-Cell Mechanotransduction
    Lipid bilayer mediates ion-channel cooperativity in a model of hair-cell mechanotransduction Francesco Gianolia, Thomas Rislerb,c,1,2, and Andrei S. Kozlova,1,2 aDepartment of Bioengineering, Imperial College London, London SW7 2AZ, UK; bLaboratoire Physico Chimie Curie, Institut Curie, PSL Research University, CNRS, 26 rue d’Ulm, 75005 Paris, France; cSorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire Physico Chimie Curie, 75005 Paris, France This manuscript was compiled on December 25, 2017 Mechanoelectrical transduction in the inner ear is a biophysical pro- constitutes an issue that is often acknowledged (2, 3, 12) but cess underlying the senses of hearing and balance. The key players still unresolved. involved in this process are mechanosensitive ion channels. They The classical model posits a single MET channel connected are located in the stereocilia of hair cells and opened by the tension to the tip link’s upper end, near myosin motors that regulate in specialized molecular springs, the tip links, connecting adjacent tip-link tension (13). Electrophysiological recordings, however, stereocilia. When channels open, the tip links relax, reducing the point to two channels per tip link (14–17), which is in accord hair-bundle stiffness. This gating compliance makes hair cells es- with its dimeric structure (18, 19). Furthermore, high-speed pecially sensitive to small stimuli. The classical explanation for the Ca2+ imaging shows that the channels are located at the tip gating compliance is that the conformational rearrangement of a sin- link’s lower end (17). This result has been corroborated by gle channel directly shortens the tip link. However, to reconcile theo- the expression patterns of key mechanotransduction proteins retical models based on this mechanism with experimental data, an within the hair bundle, which interact with protocadherin-15, unrealistically large structural change of the channel is required.
    [Show full text]
  • The Auditory Periphery 2 – Hair Cell Structure and Transduction
    The Auditory Periphery 2 – Hair Cell Structure and Transduction Dr. Elisabeth Glowatzki 955-3877 [email protected] 521 Traylor Building Websites: Promenade ‘round the cochlea (http://www.iurc.montp.inserm.fr/cric/audition/english/start.htm) Auditory Animations, Univ. of Wisconsin (http://www.neurophys.wisc.edu/animations/) Texts (at Welch or Eisenhower): From Sound to Synapse, C. D. Geisler, New York: Oxford Univ. Press, 1998 An Introduction to the Physiology of Hearing, J. O. Pickles, New York: Academic Press, 1982 Fundamentals of Hearing: An Introduction (3rd ed.), W. A. Yost, San Diego: Academic Press, 1994 Hackney CM, Furness DN (1995) Mechanotransduction in vertebrate hair cells: structure and function of the stereociliary bundle. Am. J. Physiol. 268:C1-C13. 1 The Organ of Corti Stephan Blatrix Overview over the organ of Corti One row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs), both with stereocilia bundles. The IHCs are flask-shaped, the OHCs are rod- shaped. Both have stereocilia bundles at the apex and synapses at the base. The OHC stereocilia bundles contact the tectorial membrane, the IHC stereocilia bundles seem not to contact the tectorial membrane. Innervation: 1. IHCs make 95% of afferent glutaminergic synapses (blue). 2. OHCs make 5 % of afferent synapses; their function is unknown (green). 3. OHCs make efferent cholinergic (ACh-activated synapses (red). 4. During development IHCs make have cholinergic synapses (not shown). 2 Cross sections of Organ of Corti of guinea pig. Upper from apex, lower from base of cochlear spiral. R. Pujol. Two histological sections of the organ of Corti, one apical, one basal.
    [Show full text]
  • Mechanical Amplification by Hair Cells in the Semicircular Canals
    Mechanical amplification by hair cells in the semicircular canals Richard D. Rabbitta,b,1, Richard Boylec, and Stephen M. Highsteinb aUniversity of Utah, Salt Lake City, UT 84013, bMarine Biological Laboratory, Woods Hole, MA 02543, cBioVIS Center, NASA Ames Research Center, Moffett Field, CA 94035 Edited by Michael V. L. Bennett, Albert Einstein College of Medicine, Bronx, NY, and approved January 11, 2010 (received for review June 16, 2009) Sensory hair cells are the essential mechanotransducers of the inner malian outer hair cells (19). It also has been shown that saccular ear, responsible not only for the transduction of sound and motion hair bundles of the bullfrog (20) and semicircular canal hair stimuli but also, remarkably, for nanomechanical amplification of bundles of the eel (21) move in response to transepithelial electric sensory stimuli. Here we show that semicircular canal hair cells fields and may generate physiologically relevant forces during generate a mechanical nonlinearity in vivo that increases sensitivity transduction. Hair bundles from the saccule exhibit an active to angular motion by amplification at low stimulus strengths. Sensi- process, compressive nonlinearity, that enhances mechanical tivity at high stimulus strengths is linear and shows no evidence of motion for low stimulus strengths (22), and spontaneous oscil- amplification. Results suggest that the mechanical work done by hair lations (23, 24) demonstrating the ability of the hair bundle to do cells contributes ∼97 zJ/cell of amplification per stimulus cycle, improv- mechanical work on the environment. Mechanical power output ing sensitivity to angular velocity stimuli below ∼5°/s (0.3-Hz sinusoidal and amplification by the hair bundle can be evoked by driving the motion).
    [Show full text]
  • Mechanisms of High Sensitivity and Active Amplification in Sensory Hair Cells a Dissertation Presented to the Faculty of The
    Mechanisms of High Sensitivity and Active Amplification in Sensory Hair Cells A dissertation presented to the faculty of the College of Art and Sciences of Ohio University In partial fulfillment of the requirements for the degree Doctor of Philosophy Mahvand Khamesian August 2018 © 2018 Mahvand Khamesian. All Rights Reserved. 2 This dissertation titled Mechanisms of High Sensitivity and Active Amplification in Sensory Hair Cells by MAHVAND KHAMESIAN has been approved for the Department of Physics and Astronomy and the College of Art and Sciences by Alexander B. Neiman Professor of Physics and Astronomy Joseph Shields Dean of College of Arts and Sciences 3 Abstract KHAMESIAN, MAHVAND, Ph.D., August 2018, Physics Mechanisms of High Sensitivity and Active Amplification in Sensory Hair Cells (118 pp.) Director of Dissertation: Alexander B. Neiman Hair cells mediating the senses of hearing and balance rely on active mechanisms for amplification of mechanical signals. In amphibians, hair cells exhibit spontaneous self-sustained mechanical oscillations of their hair bundles. In addition to mechanical oscillations, it is known that the electrical resonance is responsible for frequency selectivity in some inner ear organs. Furthermore, hair cells may show spontaneous electrical oscillations of their membrane potentials. In this dissertation, we study these mechanisms using a computational modeling of the bullfrog sacculus, a well-studied preparation in sensory neuroscience. In vivo, hair bundles of the bullfrog sacculus are coupled by an overlying otolithic membrane across a significant fraction of epithelium. We develop a model for coupled hair bundles in which non-identical hair cells are distributed on a regular grid and coupled mechanically via elastic springs connected to the hair bundles.
    [Show full text]
  • A Pursuit I Hearing Loss Stereocilia
    Bulletin of Environment, Pharmacology and Life Sciences Bull. Env. Pharmacol. Life Sci., Vol 9[3] February 2020 :72-79 ©2020 Academy for Environment and Life Sciences, India Online ISSN 2277-1808 Journal’s URL:http://www.bepls.com CODEN: BEPLAD Global Impact Factor 0.876 Universal Impact Factor 0.9804 NAAS Rating 4.95 REVIEW ARTICLE OPEN ACCESS Tip links and Top Connector Proteins in Stereocilia: a pursuit in hearing loss Priyanka P Urade1, Surabhi V Barde1 Shubhangi K Pingle*3, Rajani G Tumane3, Aruna A Jawade3, Nidhi K.Meshram2, Piyush V Shende2, Shardul S. Wagh1 1Kamla Nehru Mahavidyalaya, Sakkardara Chowk, Nagpur -9 (M.S.), India. 2Dr. Ambedkar College Nagpur, Deekshabhoomi, Nagpur, Maharashtra 440010. 3National Institute of Miners’ Health, JNARDDC Campus, Opposite Wadi Police Station, Amravati road, Wadi, Nagpur 440 023, (M.S.), India. *Corresponding author's E-mail: [email protected] ABSTRACT Hearing depends on the functioning of sensitive micromachinary of the inner ear cochlea. The sound vibrations received in the cochlea is amplified through stereocilia of the hair cells gated by the tip links. Proteins anchoring to the tip link to the cytoskeleton in the stereociliary links to cadherin 23 and protocadherin 15 are the part of the regulatory process that forms the actin core and the transduction apparatus. The tip links and lateral links are maintaining optimal bundle cohesion and stiffness for transduction. The loss of cross-links of the outer hair cells resulting in disarrangement of the stereociliary bundles are the result of Noise Induction leads to permanent sensorineural hearing loss. This review summarizes about the structure, function and composition of stereociliary linkages of the links and how they are relevant to human hearing impairment.
    [Show full text]
  • CHP1.PDF (39.81Kb)
    Chapter 1. Introduction The vestibular sense enables vertebrates to perceive motion of the skull, as well as the force of gravity. This sense is essential to balance, posture, and visual fixation. The vestibular system is responsible for the vestibular sense. The vestibular system relies upon a complex cascade of events to transform the input signal (motion or gravity) into a nerve signal received and interpreted by the brain (figure 1-1). This dissertation is concerned with a small portion of this process: the deflection of the ciliary bundles of hair cells. Head motion/Gravity Gel deformation or Endolymph Velocity Geometry and Dimensions Force applied to ciliary bundle Ciliary bundle stiffness Ciliary bundle deflection Material Properties Mechanoelectrical transduction Modulation of receptor potential Output to central nervous system Figure 1-1. Diagram showing the cascade of events needed to detect motion in the vestibular system. The scope of this dissertation is shaded in gray. Where relevant, the processes in the white boxes shown above will be discussed in detail later in this chapter. Hair cells form the final mechanical link in the vestibular system. They are generic displacement transducers that are also found in hearing organs and on the lateral line of fishes, for vibration sensing. Although this work is primarily concerned with the response of vestibular hair cells, its methods and conclusions can be applied to hair cell research in other systems. 1 This dissertation looks at modeling mechanical aspects of the hair cells’ ciliary bundles. It will establish several new techniques which greatly expand current models of hair cell bundles.
    [Show full text]
  • Analysis of the Dynamic Behavior of the Inner Hair Cell Stereocilia by the Finite Element Method∗
    828 Analysis of the Dynamic Behavior of the Inner Hair Cell Stereocilia by the Finite Element Method∗ Toshihiro MATSUI∗∗, Chihiro NAKAJIMA∗∗, Yuichi YAMAMOTO∗∗, Masayoshi ANDOH∗∗, Koji IIDA∗∗, Michio MURAKOSHI∗∗, Shun KUMANO∗∗ and Hiroshi WADA∗∗ The motion of the inner hair cell (IHC) stereocilia, which results in tension in the tip links connected to mechanically gated ion channels, mediates the auditory transduction proc- ess. However, it is difficult to directly observe the motion of the stereocilia because of their minute dimensions and complex structure. In this study, to investigate such motion, a fi- nite element method model of the tall, middle and short IHC stereocilia, including the tip and lateral links extending between the stereocilia, was constructed. By applying an analyt- ically estimated fluid force caused by a stimulus of 60 dB SPL at 500 Hz to the model, the dynamic behavior of the stereocilia was analyzed. Numerical results showed that the stere- ocilia moved in phase and that the maximum tensions of 2.5 fN and 2.1 fN occurred in the tip link connecting the tall and middle stereocilia and in the tip link connecting the middle and short stereocilia, respectively. By contrast, under the condition in which the lateral links were removed, maximum tension in the former increased to 11.6 fN, while that in the latter only increased to 2.3 fN. It was therefore suggested that the lateral links protect the MET channels located at taller stereocilia against large stimuli and subject the channels located in the same IHC to forces of similar size. Key Words: Acoustic, Biomechanics, Finite Element Method, Sound, Cochlea, Hair Cell, Stereocilia Figure 3 shows a cross section of the OC.
    [Show full text]
  • The Tip-Link Antigen, a Protein Associated with the Transduction Complex of Sensory Hair Cells, Is Protocadherin-15
    7022 • The Journal of Neuroscience, June 28, 2006 • 26(26):7022–7034 Cellular/Molecular The Tip-Link Antigen, a Protein Associated with the Transduction Complex of Sensory Hair Cells, Is Protocadherin-15 Zubair M. Ahmed,1‡ Richard Goodyear,2‡ Saima Riazuddin,1* Ayala Lagziel,1* P. Kevin Legan,2 Martine Behra,3 Shawn M. Burgess,3 Kathryn S. Lilley,4 Edward R. Wilcox,5 Sheikh Riazuddin,6 Andrew J. Griffith,1 Gregory I. Frolenkov,7 Inna A. Belyantseva,1 Guy P. Richardson,2 and Thomas B. Friedman1 1Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850, 2School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom, 3Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, 4Cambridge Center for Proteomics, Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom, 5DNA Sequencing Center, Department of Integrative Biology, Brigham Young University, Provo, Utah 84602, 6National Centre of Excellence in Molecular Biology, Lahore, Pakistan, and 7Department of Physiology, University of Kentucky, Lexington, Kentucky 40536 Sound and acceleration are detected by hair bundles, mechanosensory structures located at the apical pole of hair cells in the inner ear. The different elements of the hair bundle, the stereocilia and a kinocilium, are interconnected by a variety of link types. One of these links, the tip link, connects the
    [Show full text]