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1
Jagger, Daniel James. "Modulation of ion channels in outer hair cells from the mammalian cochlea." Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336876.
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Richmond, Sarah Jane. "A study of in situ outer hair cells from the adult mammalian cochlea." Thesis, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313691.
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Gale, Jonathan Edward. "Mechanosensitivity of the basolateral membrane of outer hair cells from the mammalian cochlea." Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240651.
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Liang, Guihua. "K⁺ channels in the inner ear : electrophysiological and molecular studies /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7349-971-4/.
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Abou, Dakka Milad. "Linear oscillatory dynamics of flexoelectric membranes embedded in viscoelastic media with applications to outer hair cells." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114535.
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Membrane flexoelectricity is an electromechanical coupling effect between the membrane average curvature and macroscopic electric polarization. Flexolelectricity is a biological actuation mechanism involved in the functioning of hearing. This thesis uses theory and simulation to develop a fundamental understanding of flexolectricity of relevance to hearing processes by integrating membrane elasticity and flexolectricity with viscoelastic processes. Flexoelectric actuation uses an imposed electric field to create membrane bending. In this thesis we model the small amplitude oscillatory dynamics of a membrane immersed in viscoelastic media driven by a small amplitude harmonic electric field. The model is based on the integration of the flexoelectric membrane shape equation applied to a circular membrane attached to the inner surface of a circular capillary and the coupled capillary flow of the contacting viscoelastic phases, such that the membrane flexoelectric oscillations drive periodic viscoelastic capillary flows. The model for curvature dynamics as a function of the electric field is second order in both inputs and outputs and maps into the mechanical Burgers solid model. The material space of the viscoelastic fluid/flexoelectric membrane material system is defined and used to classify and characterize the frequency response of the material system. The frequency response is characteristic of a second order system with a second order input and displays a single resonant peak in the complex curvature and the total power. The amplitude, frequency and width of the power peak, of relevance to the functioning of outer hair cells is dependent on the inertia emerging from the contacting viscoelastic phases and the ratio between the membrane elasticity and the elasticity of contacting liquids. The integrated flexoelectric/viscoelastic model and the novel findings contribute to the ongoing quest for a fundamental understanding of the functioning of outer hair cells.La flexoélectricité de une membrane est un effet d'accouplement électromécanique entre la membrane, la courbure moyenne et la divergence électrique macroscopique. La flexolélectricité est un mécanisme de commande biologique impliqué dans le fonctionne d'audience. Cette thèse utilise la théorie et la simulation pour développer une compréhension fondamentale de "flexolectricity" de pertinence aux processus d'audience en intégrant l'élasticité de membrane et flexolectricity avec les processus de viscoelastique. La mise en action "Flexoelectric" utilise un champ électrique imposé pour créer la membrane qui courbe. Dans cette thèse nous modelons la petite amplitude dynamique oscillatoire d'une membrane immergée dans les médias viscoelastiques motivés par une petite amplitude un champ électrique harmonique. Le modèle est fondé sur l'intégration de l'équation de forme de membrane flexoelectrique s'est appliqué à une membrane circulaire attachée à la surface intérieure d'un capillaire circulaire et le flux capillaire couplé des phases viscoelastiques contactant, tel que les oscillations flexoelectriques de membrane conduisent les flux capillaires viscoelastiques. Le modèle pour la dynamique de courbure comme une fonction du champ électrique est le deuxième ordre dans les données et les productions et les cartes dans les mécaniques de modèle solide (modele Burger). L'espace matériel de la membrane de fluide/flexoelectrique/viscoelastique et le système matériel sont définis et classifiés et la réponse de fréquence du système matériel est caracterise. La réponse de fréquence est la caractéristique d'un deuxième système d'ordre avec une deuxièmes données d'ordre et affiche un sommet résonnant seul dans la courbure complexe et le pouvoir total. L'amplitude, la fréquence et la largeur du sommet de pouvoir, de pertinence au fonctionner de cellules de cheveux extérieures dépend de l'inertie naissante des phases de viscoelastic contactant et la proportion entre l'élasticité de membrane et l'élasticité de contacter des liquides. Le modèle intégré "flexoelectric/viscoelastic" et les conclusions originales contribuent à la quête continuante pour une compréhension fondamentale du fonctionnement des "Outer Hair Cells".
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Spreadbury, Ian Clive. "Single channel recordings form the BK channels of outer hair cells of the guinea pig cochlea." Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322611.
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Roberts, Terri Patricia. "Developmental failure in cochlear hair cells from mouse models of Usher syndrome and the identification of an acid sensitive ionic current in Inner and Outer hair cells." Thesis, University of Sussex, 2013. http://sro.sussex.ac.uk/id/eprint/46460/.
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Inner hair cells (IHCs) are the primary sensory receptors of the mammalian cochlea. I employed the whole-cell patch-clamp technique to study voltage responses and ionic currents of IHCs in mice bearing mutations in hair bundle proteins. These mutations, all associated with Usher syndrome, lead to structural and functional defects of the mechanosensory hair bundle. I observed developmental failure in the electrical properties of IHCs from these mutants: a continuation of neonatal spiking instead of the graded receptor potentials seen in control adult IHCs. Voltage-clamp recordings revealed the main cause as the absence of the adult fast potassium (IK,f) current. Outer hair cells (OHCs) are required to amplify the travelling wave to be detected by the IHCs. Optical and whole-cell patch clamp techniques in these same mutants were employed to investigate the development of adult OHCs. I observed a developmental failure in the electrical properties of these OHCs, seen by an absence of the potassium current IK,n. Electromotility and the associated non-linear capacitance were however observed, indicating that prestin is expressed in the mutants. Acid sensitive ion channels (ASICs) have recently been found to be present within the organ of Corti. Here I present data showing the presence of an acid sensitive ion current in both IHCs and OHCs. ASIC1b knockout mice show a response to changes in the extracellular pH suggesting that the current may be carried through a different channel subtype or that compensatory changes occur. The electrical properties of the IHCs develop to maturity in these mice, however the OHCs appear to remain functionally immature displaying a lack of expression of the IK,n current and electromotily. This lack of electromotile function suggests that ASIC1b may be required either for the function of prestins electromotility or for the targeting of prestin to the cell membrane.
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Wilson, Caroline Lesley. "The hair follicle : studies of the outer root sheath in health and disease, and a possible role for the bulge." Thesis, Imperial College London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309741.
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Leitner, Michael [Verfasser], and Dominik [Akademischer Betreuer] Oliver. "Molecular Properties and Pathophysiological Relevance of the Predominant K+ Conductance in Cochlear Outer Hair Cells / Michael Leitner. Betreuer: Dominik Oliver." Marburg : Philipps-Universität Marburg, 2012. http://d-nb.info/1027183662/34.
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Wright, Daniel. "Anatomical and electrophysiological investigation of the distribution of acetylcholine receptors in the post synaptic membrane of mammalian cochlear outer hair cells." Thesis, Keele University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250420.
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Shiraishi, Hisako. "Design of an Analog VLSI Cochlea." University of Sydney. Electrical and Information Engineering, 2003. http://hdl.handle.net/2123/556.
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The cochlea is an organ which extracts frequency information from the input sound wave. It also produces nerve signals, which are further analysed by the brain and ultimately lead to perception of the sound. An existing model of the cochlea by Fragni`ere is first analysed by simulation. This passive model is found to have the properties that the living cochlea does in terms of the frequency response. An analog VLSI circuit implementation of this cochlear model in CMOS weak inversion is proposed, using log-domain filters in current domain. It is fabricated on a chip and a measurement of a basilar membrane section is performed. The measurement shows a reasonable agreement to the model. However, the circuit is found to have a problem related to transistor mismatch, causing different behaviour in identical circuit blocks. An active cochlear model is proposed to overcome this problem. The model incorporates the effect of the outer hair cells in the living cochlea, which controls the quality factor of the basilar membrane filters. The outer hair cells are incorporated as an extra voltage source in series with the basilar membrane resonator. Its value saturates as the input signal becomes larger, making the behaviour rather closer to that of a passive model. The simulation results show this nonlinear phenomenon, which is also seen in the living cochlea. The contribution of this thesis is summarised as follows: a) the first CMOS weak inversion current domain basilar membrane resonator is designed and fabricated, and b) the first active two-dimensional cochlear model for analog VLSI implementation is developed.
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Syam, Diana. "Immobilizing Mutation in an Unconventional Myosin15a Affects not only the Structure of Mechanosensory Stereocilia in the Inner Ear Hair Cells but also their Ionic Conductances." UKnowledge, 2014. http://uknowledge.uky.edu/medsci_etds/2.
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In the inner and outer hair cells (OHCs) of the inner ear, an unconventional myosin 15a localizes at the tips of mechanosensory stereocilia and plays an important role in forming and maintaining their normal structure. A missense mutation makes the motor domain of myosin 15a dysfunctional and is responsible for the congenital deafness DFNB3 in humans and deafness and vestibular defects in Shaker-2 (Sh2) mouse model. All hair cells of homozygous Shaker-2 mice (Myo15sh2/sh2) have abnormally short stereocilia, but, only stereocilia of Myo15sh2/sh2OHCs start to degenerate after the first few days of postnatal development and lose filamentous tip links between stereocilia that are crucial for mechanotransduction. The exact mechanisms of this degeneration are unknown even though they may underlie DFNB3 deafness in humans. We hypothesize that structural abnormalities in Myo15sh2/sh2 OHCs may alter the mechanical forces applied to the mechano-electrical transduction (MET) channels resulting in abnormal ionic homeostasis, which may lead to eventual degeneration of Myo15sh2/sh2 OHCs. Therefore, we investigated the ionic conductances and integrity of mechanotransduction apparatus in Myo15sh2/sh2 OHCs. Surprisingly, we found that myosin 15a-deficiency is associated not only with structural abnormalities of OHC stereocilia but also with alterations of voltage-gated ion conductances.
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Murugasu, Euan. "In-vivo measurements of basilar membrane displacement in the basal turn of the guinea pig cochlea : evidence for the role of outer hair cells in active cochlear mechanics." Thesis, University of Sussex, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318941.
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O'Beirne, Greg A. "Mathematical modelling and electrophysiological monitoring of the regulation of cochlear amplification." University of Western Australia. School of Biomedical and Chemical Sciences, 2005. http://theses.library.uwa.edu.au/adt-WU2006.0115.
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[Truncated abstract] The cochlea presumably possesses a number of regulatory mechanisms to maintain cochlear sensitivity in the face of disturbances to its function. Evidence for such mechanisms can be found in the time-course of the recovery of CAP thresholds during experimental manipulations, and in observations of slow oscillations in cochlear micromechanics following exposure to low-frequency tones (the “bounce phenomenon”) and other perturbations. To increase our understanding of these oscillatory processes within the cochlea, and OHCs in particular, investigations into cochlear regulation were carried out using a combination of mathematical modelling of the ionic and mechanical interactions likely to exist within the OHCs, and electrophysiological experiments conducted in guinea pigs. The electrophysiological experiments consisted of electrocochleographic recordings and, in some cases, measurement of otoacoustic emissions, during a variety of experimental perturbations, including the application of force to the cochlear wall, exposure to very-low-frequency tones, injection of direct current into scala tympani, and intracochlear perfusions of artificial perilymph containing altered concentrations of potassium, sodium, and sucrose. To obtain a panoramic view of cochlear regulation under these conditions, software was written to enable the interleaved and near-simultaneous measurement of multiple indicators of cochlear function, including the compound action potential (CAP) threshold, amplitude and waveshape at multiple frequencies, the OHC transfer curves derived from low-frequency cochlear microphonic (CM) waveforms, distortion-product otoacoustic emissions (DPOAEs), the spectrum of the round-window neural noise (SNN), and the endocochlear potential (EP). ... The mathematical model we have developed provided a physiologically-plausible and internally-consistent explanation for the time-courses of the cochlear changes observed during a number of different perturbations. We show that much of the oscillatory behaviour within the cochlea is consistent with underlying oscillations in cytosolic calcium concentration. We conclude that a number of the discrepancies between the simulation results and the experimental data can be resolved if the cytosolic calcium functions as two distinct pools: one which controls basolateral permeability and one which controls slow motility. This two-calcium-pool model is discussed.
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Lu, Timothy K. (Timothy Kuan-Ta) 1981. "A feedback analysis of outer hair cell dynamics." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/29677.
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Thesis (M.Eng. and S.B.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2003.Includes bibliographical references (leaves 144-146).
Outer hair cells (OHCs) generate active forces in the mammalian cochlea. Acting as cochlear amplifiers, OHCs can counteract viscous drag, generating high gain at characteristic frequencies and allowing for the sharp frequency selectivity and sensitivity observed in mammals. Excitatory displacement of the basilar membrane causes depolarization of OHC membrane potentials which results in contraction. The motor protein prestin is driven by receptor potentials. However, low-pass filtering by the plasma membrane should severely attenuate the receptor potential at high frequencies (> 100 kHz) where mammalian hearing has been observed. Thus, an open question is how OHCs can respond at these high frequencies despite their low frequency cutoff. Inspired by the use of feedback in mechanical and electrical systems to accelerate slow poles, I demonstrate that negative feedback from the coupling of two mechanical modes of vibration can lead to a membrane time constant speedup and a sharpening of the mechanical response.
y Timothy K. Lu.
M.Eng.and S.B.
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Körbes, Daiane. "TOXICIDADE DE AGROTÓXICO ORGANOFOSFORADO NO SISTEMA AUDITIVO PERIFÉRICO DE COBAIAS: ESTUDO ANATÔMICO E FUNCIONAL." Universidade Federal de Santa Maria, 2009. http://repositorio.ufsm.br/handle/1/6461.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorThe organophosphate pesticides are widely used in agriculture, and the widespread application of these agents, without the appropriate use of bio-security measures, has contributed to environmental degradation and the increased incidence of occupational poisoning, becoming one of the main public health problems in rural areas. Studies show that the ototoxic agents, in addition to the peripheral vestibular and auditory systems compromise, also impair central auditory pathways. Among the major toxic agents that can lead to hearing loss are the solvents, metals, suffocating and organophosphate pesticides. This study examined the acute ototoxic action of a pesticide on the peripheral auditory system. This is a prospective experimental study. We used male albino guinea pigs, divided into three groups, which was administered distilled water (group 1 - control), pesticide - 0.3 mg/Kg/day (group 2), pesticide - 3 mg/Kg/day (group 3), for seven consecutive days. The pesticide used was Tamaron® (methamidophos). The auditory functional evaluation was performed using the Distortion Product Otoacoustic Emissions (DPOAE) and Auditory Brainstem Response (ABR), both performed before and immediately after the application of the pesticide. The anatomical assessment was performed with scanning electron microscopy. The guinea pigs subjected to pesticide had cochlear morphological changes, with lesions in three turns examined in electron microscopy, which was increased according to the dosage received from the agent. In all animals the DPOAE was present, but it was verified that the signal/noise ratio of the frequencies of 1.500 and 6.000 Hz in DPOAE of groups 2 and 3 showed statistically significant difference when compared to control group, indicating possible cell impairment. There were no statistically significant changes in functional assessment of VIII nerve when evaluated by wave I of ABR. It is concluded that the organophosphorous can be considered as a harmful acute agent of outer hair cells, seen the correlation between the dose applied and the amount of changes observed by electron microscopy, however, the acute exposure to Tamaron® did not cause functional alteration of the peripheral auditory system.
Os agrotóxicos organofosforados são amplamente utilizados na agricultura, e a elevada aplicação desses agentes, sem o emprego das devidas medidas de biossegurança, vem contribuindo para a degradação ambiental e para o aumento da incidência de intoxicação ocupacional, tornando-se um dos principais problemas de saúde pública no meio rural. Pesquisas demonstram que os agentes ototóxicos, além de comprometer os sistemas auditivo e vestibular periféricos, provocam ainda alterações nas vias auditivas centrais. Dentre os principais agentes químicos que podem levar à perda auditiva incluem-se os solventes, os metais, os asfixiantes e os agrotóxicos organofosforados. O objetivo deste estudo foi analisar a ação ototóxica aguda de um agrotóxico do grupo dos organofosforados no sistema auditivo periférico. Trata-se de um estudo experimental prospectivo, realizado em cobaias albinas machos, divididas em três grupos, nos quais se administrou água destilada (grupo 1 - controle), agrotóxico - 0,3mg/Kg/dia (grupo 2), agrotóxico 3 mg/Kg/dia (grupo 3), durante sete dias consecutivos. O agrotóxico utilizado foi Tamaron® (metamidofós). A avaliação auditiva funcional foi realizada utilizando-se Emissões Otoacústicas Produto de Distorção (EOAPD) e Potencial Evocado Auditivo de Tronco Encefálico (PEATE), ambos realizados antes e imediatamente após o período de aplicação do agrotóxico. A avaliação anatômica foi realizada com Microscopia Eletrônica de Varredura. As cobaias submetidas ao agrotóxico apresentaram alterações morfológicas cocleares, com lesões nas três espiras analisadas na microscopia eletrônica, intensificadas de acordo com a dosagem recebida do agente. Na avaliação auditiva funcional, todas as cobaias apresentaram EOAPD presentes, no entanto verificou-se significância estatística nos valores da relação sinal/ruído das frequências de 1.500 e 6.000 Hz das EOAPD das cobaias dos grupos 2 e 3 quando confrontados com os achados dos animais do grupo controle, indicando um possível sofrimento celular. Não foram encontradas alterações estatisticamente significantes na avaliação do VIII par craniano por meio da análise da onda I do PEATE. Concluiu-se que o organofosforado pode ser considerado um agente lesivo agudo das células ciliadas externas visto a correlação entre a dosagem aplicada e a quantidade de alterações observadas à microscopia eletrônica, entretanto a exposição aguda ao Tamaron® não causou alteração funcional do sistema auditivo periférico.
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Muallem, Daniella. "An anion transporter theory of the outer hair cell motor protein." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1444859/.
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This thesis addresses the mechanism of electromotility in outer hair cells (OHCs) of the mammalian cochlea. Prestin, a protein densely packed in the lateral membrane is assumed to drive electromotility. A current hypothesis is that prestin is an incomplete transporter, shuttling chloride across the membrane without allowing it to dissociate at the extracellular surface. In this thesis kinetic models are formulated to show that this hypothesis cannot reproduce the previously published experimental data from electrical recordings. However an alternative model of prestin as an anion exchanger (modelled here as a chloride/sulphate exchanger) is formulated, which can reproduce many of the experimental observations. In this model the experimentally observed charge movements across the cell membrane are produced by the translocation of a chloride ion combined with some intrinsic charged residues. To further test the predictions of the model, patch clamp recordings were performed on dissociated OHCs, in the excised patch and whole-cell configurations. The OHC non-linear capacitance (NLC) depended on the concentration of intracellular chloride (Clj). When Clj was removed from internal and external solutions, a residual NLC (-15- 30%) was found, which was consistent with the predictions of the model for contaminant levels of Clj ( 10uM). Additionally the effect on the NLC of reducing Clj depended on the species of anion used to replace Clj. The largest effect was produced by replacement with sulphate, whilst the smallest effect was produced by replacement with glutamate. These findings support the model. Finally two potential causes for previous controversy in the literature were identified. 1) The NLC depended on the recording configuration when Clj was reduced below 1-1 OmM. 2) The dependence of the NLC on Clj was affected when Tris+ replaced Na+ as the major cation in solutions.
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Souchal, Marion. "Surdités cachées ; atteinte des cellules sensorielles cochléaires ou du nerf auditif ?" Thesis, Université Clermont Auvergne (2017-2020), 2017. http://www.theses.fr/2017CLFAS003/document.
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Les surdités neurosensorielles sont classiquement décrites par une élévation des seuils auditifs généralement corrélée à une dégénérescence des cellules ciliées externes (CCE). Toutefois, des travaux récents sur des modèles animaux ont montré qu’un audiogramme normal pouvait être associé à des atteintes auditives périphériques. Ce travail de thèse a contribué à mieux caractériser chez des modèles murins, ces déficiences supraliminaires cachées liées d’une part, à des altérations des CCE et d’autre part, à la dégénérescence de certaines fibres nerveuses auditives. Dans la première partie de cette thèse, l’évolution des profils auditifs de souris présentant une dégénérescence accélérée des CCE, les souris de souche CD1-RjOrl : SWISS, a été caractérisée. Dans cette étude longitudinale, menée au cours du premier mois postnatal, une progressivité de la déficience auditive a été montrée. Toutefois, une discordance surprenante a été mise en évidence entre des seuils auditifs proches des valeurs normales à haute fréquence combinés à des produits de distorsions acoustiques (PDA) absents. Les courbes d’accord de masquage montrent un décalage des pointes vers les basses fréquences. Ces données indiquent que les CCE de la base ne sont plus fonctionnelles et que la perception des hautes fréquences est perturbée. Les observations en microscopie électronique à balayage ont révélé une conformation anormale de la touffe stéréociliaire des CCE au niveau de la base de la cochlée. Ces données témoignent d’une désorganisation de la tonotopie cochléaire. Dans la deuxième partie de cette thèse, l’effet de l’oxaliplatine sur la fonction auditive et sur la morphologie cochléaire a été décrit chez des souris adultes de souche CBA/J. L’oxaliplatine, un sel de platine utilisé en chimiothérapie, a de nombreux effets secondaires parmi lesquels l’apparition d’une neuropathie périphérique. À la suite d’un traitement avec cette drogue, les souris ne présentent pas d’élévation des seuils auditifs et pas d’altération de la fonction des CCE. Cependant, l’étude histologique révèle une dégénérescence surprenante des fibres auditives du ganglion spiral. Avec des tests électrophysiologiques supplémentaires, une diminution de l’amplitude du potentiel d’action composite a été mise en évidence. Le réflexe du système efférent olivocochléaire médian, évalué par un test de suppression controlatéral, semble également être diminué par le traitement. Les souris traitées avec de l’oxaliplatine constituent donc un modèle animal précieux de surdité cachée, qui demande à être mieux caractérisé. Les résultats de ces études confirment l’insuffisance de l’audiogramme pour détecter des altérations subtiles de la cochlée et montrent la nécessité d’améliorer le diagnostic de ces déficiences supraliminaires. Ainsi, les atteintes cachées des CCE peuvent être détectées par l’absence de PDA associée à des potentiels évoqués auditifs normaux et les neuropathies par des PDA présents associés à des potentiels évoqués auditifs anormaux. La combinaison de ces différents tests fonctionnels et électrophysiologiques permettrait une meilleure prise en charge des patients et une amélioration de leur qualité de vieSensorineural hearing loss are classically described by auditory thresholds elevation usually correlated with outer hair cells (OHC) degeneration. However, recent work on animal models has shown that normal audiogram can be associated with peripheral hearing impairments. This thesis contributed to better characterize, in mouse models, these hidden supraliminal deficiencies related on the one hand, with OHC alterations and on the other, to auditory nerve fibers degeneration. In the first part of this thesis, the auditory profiles evolution of mice exhibiting an OHC accelerated degeneration, the CD1-RjOrl: SWISS strain mice, was characterized. In this longitudinal study, conducted in the first postnatal month, a progressivity of the hearing impairment has been observed. However, a surprising discrepancy was found between high frequency hearing thresholds close to normal values associated with missing distortion product otoacoustic emission (DPOAE). The masking tuning curves dips are shifted toward low frequencies. Those data indicate that basal OHC are no longer functional and the perception of high frequencies is disrupted. Observations in scanning electron microscopy revealed an abnormal conformation of the OHC stereocilia bundles at the cochlea base. These results represent an evidence of a disorganized cochlear tonotopy. In the second part of this thesis, the effect of oxaliplatin on the auditory function and on the cochlear morphology was described in adult CBA/J strain mice. Oxaliplatin, a platinum salt used in chemotherapy, has many side effects including development of peripheral neuropathy. Following one treatment with this drug, mice did not present any hearing threshold elevation or OHC function impairment. However, the histological study reveals a surprising degeneration of the spiral ganglion cells. With additional electrophysiological tests, a decrease in the compound action potential amplitude has been demonstrated. The median olivocochlear efferent system reflex, evaluated by a contralateral suppression test, also seems to be diminished by the treatment. The mice treated with oxaliplatin, therefore constitute a precious animal model of hidden deafness, which needs to be better characterized. The results of these studies confirm the audiogram insufficiency to detect subtle cochlea alterations and reveal the need to improve supraliminal deficiencies diagnosis. Thus, hidden OHC impairments can be detected by the absence of DPOAE associated with normal auditory evoked potentials and neuropathies by the presence of DPOAE associated with abnormal auditory evoked potentials. The combination of these functional and electrophysiological tests would allow better management of patients and an improvement in their quality of life.Keywords: hidden hearing loss, CD1 mice, outer hair cells, masking tuning curves, tonotopy, oxaliplatine, spiral
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Jiang, Beibei. "A biophysical model of the role of the outer hair cell in cochlear nonlinearity." Thesis, University of Plymouth, 2010. http://hdl.handle.net/10026.1/2235.
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It has been observed that the response characteristics of the basilar membrane in normal living cochleae are both frequency and level-sensitive (Robles & Ruggero 2001). The quality factor of the tuning curve is large at low sound levels and decreases as the sound level increases, and the peak of the tuning curve moves towards lower frequencies as the sound level increases. The current study proposes a nonlinear cochlear model that responds adaptively to the incoming sounds via feedback control arising from the mechanical attributes of the cochlear partition. These attributes are dependent on the membrane potential of the outer hair cells (He & Dallos 1999, Santos-Sacchi 1992). A parallel resistor-capacitor circuit analogy of the outer hair cell with related perilymph and endolymph potentials is designed to simulate sound-evoked changes in the outer hair cell membrane potential. Nonlinear responses of the cochlea, such as compression and two tone suppression, can be explained using this model. Furthermore, it has been shown that the basilar membrane response to pure tone stimuli is attenuated by directly stimulating the medial olivo-cochlear bundle using electrical shocks (Cooper & Guinan 2006). Basilar membrane responses in the presence of efferent stimulation can be demonstrated using the same model, through modulation of the outer hair cell rnembrane potential. The proposed model provides a unified account of the combined effect of sounds and efferent stimulation on cochlear responses.
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Bell, James Andrew, and andrew bell@anu edu au. "The Underwater Piano: A Resonance Theory of Cochlear Mechanics." The Australian National University. Research School of Biological Sciences, 2006. http://thesis.anu.edu.au./public/adt-ANU20080706.141018.
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This thesis takes a fresh approach to cochlear mechanics. Over the last
quarter of a century, we have learnt that the cochlea is active and highly tuned,
observations suggesting that something may be resonating. Rather than accepting the standard traveling wave interpretation, here I investigate whether a resonance theory of some kind can be applied to this remarkable behaviour.¶
A historical survey of resonance theories is first conducted, and advantages
and drawbacks examined. A corresponding look at the traveling wave theory
includes a listing of its short-comings.¶
A new model of the cochlea is put forward that exhibits inherently high
tuning. The surface acoustic wave (SAW) model suggests that the three rows of outer hair cells (OHCs) interact in a similar way to the interdigital transducers of an
electronic SAW device. Analytic equations are developed to describe the conjectured interactions between rows of active OHCs in which each cell is treated as a point source of expanding wavefronts. Motion of a cell launches a wave that is sensed by the stereocilia of neighbouring cells, producing positive feedback. Numerical calculations confirm that this arrangement provides sharp tuning when the feedback gain is set just below oscillation threshold.¶
A major requirement of the SAW model is that the waves carrying the feedback have slow speed (5-200 mm/s) and high dispersion. A wave type with the
required properties is identified - a symmetric Lloyd-Redwood wave (or squirting wave) - and the physical properties of the organ of Corti are shown to well match those required by theory.¶
The squirting wave mechanism may provide a second filter for a primary
traveling wave stimulus, or stand-alone tuning in a pure resonance model. In both, cyclic activity of squirting waves leads to standing waves, and this provides a physical rendering of the cochlear amplifier.
In keeping with pure resonance, this thesis proposes that OHCs react to the
fast pressure wave rather than to bending of stereocilia induced by a traveling wave. Investigation of literature on OHC ultrastructure reveals anatomical features consistent with them being pressure detectors: they possess a cuticular pore (a small compliant spot in an otherwise rigid cell body) and a spherical body within (Hensens
body) that could be compressible. I conclude that OHCs are dual detectors, sensing displacement at high intensities and pressure at low. Thus, the conventional traveling wave could operate at high levels and resonance at levels dominated by the cochlear
amplifier. ¶
The latter picture accords with the description due to Gold (1987) that the cochlea is an underwater piano - a bank of strings that are highly tuned despite immersion in liquid.¶
An autocorrelation analysis of the distinctive outer hair cell geometry shows
trends that support the SAW model. In particular, it explains why maximum
distortion occurs at a ratio of the two primaries of about 1.2. This ratio also produces near-integer ratios in certain hair-cell alignments, suggesting that music may have a cochlear basis.¶
The thesis concludes with an evaluation and proposals to experimentally test
its validity.
21
Battaglia, Alex. "Ras activation contributes to outer hair cell apoptosis in the basal turn of the cochlea after cisplatin and gentamicin exposure /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2002. http://wwwlib.umi.com/cr/ucsd/fullcit?p3064454.
Full text
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Freeman, Jessica. "Short-term effects of simultaneous cardiovascular workout and personal music device use on the otoacoustic emissions of young adults." Diss., University of Pretoria, 2014. http://hdl.handle.net/2263/46259.
Full textAbstract:
Recent advances in the field of audiology have indicated that there has been a growing concern regarding the potential damage to the hearing mechanism induced by recreational noise exposure from personal music devices (PMD). Regular PMD use may have a long-term damaging effect on the outer- and inner hair cells of the cochlea which may result in a progressive hearing loss. As PMDs have advanced to a stage where the memory of the devices are able to contain hours of listening content, the environments where these devices are being used are rapidly expanding. Many young adults tend to use their PMDs whilst exercising. Exercise in itself induces physiological and metabolic changes such as increased blood flow and oxygen levels within the structures of the cochlea.
The purpose of this study was to determine the differential impact and short-term effects of simultaneous cardiovascular workout and personal music device (PMD) use on the otoacoustic emissions of young adults. Seven female and five male subjects completed three testing conditions: (i) one hour exposure to PMD use in isolation, (ii) one hour exposure to cardiovascular workout in isolation, and (iii) one hour simultaneous exposure to PMD use and cardiovascular workout. Distortion product otoacoustic emissions (DPOAEs) were conducted prior to, as well as directly following each testing condition, as primary indicator of cochlear responses emitted through a preset stimulus frequency sequence measuring the 2f₁ - f₂ (75 – 70 dB SPL) and constructing a plot of DPOAE levels as a function of frequency.
While each of the testing conditions on its own did not result in statistically significant changes of the DPOAE response, a highly significant different profile in the DPOAE response level increase/decrease for the higher frequencies (6-8 kHz) was obtained when comparing the different sessions to each other. Where exposure to cardiovascular workout showed a clear trend of an increased DPOAE response level between the pre-exposure and post-exposure testing from 2 kHz to 8 kHz with a maximum increase at 6 kHz, both the music only condition and the combined condition where the cardiovascular workout was combined with music resulted in a significant different profile. During combined exposure a clear trend of decreased DPOAE response amplitudes between the pre-exposure and post-exposure testing were seen for the higher frequencies. These findings may support the notion of a clear effect of cardiovascular workout on the otoacoustic emissions at higher test frequencies, measured by DPOAEs when performed with and without music exposure.Dissertation (MLOG)--University of Pretoria, 2014.
tm2015
Speech-Language Pathology and Audiology
MLOG
Unrestricted
23
Harrison, Ryan T. "Effect of Changes to the Circadian Rhythm on Susceptibility to Noise- and Drug-Induced Hearing Losses." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1574719906038686.
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Gilbert, Benjamin Lawrence. "ACF7 DEFICIENCY DOES NOT IMPAIR AUDITORY HAIR CELL DEVELOPMENT OR HEARING FUNCTION." Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1619801135718899.
Full text
25
Nam, Hui S. Ph D. (Hui Sok) Massachusetts Institute of Technology. "Low-frequency bias-tone effects on auditory-nerve responses to clicks and tones : investigating multiple outer-hair-cell actions on auditory-nerve firing." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/68455.
Full textAbstract:
Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2011.Cataloged from PDF version of thesis.
Includes bibliographical references.
Active motility in outer hair cells (OHCs) amplifies basilar-membrane (BM) and auditory-nerve (AN) responses to low-level sounds. The recent finding that medial olivocochlear (MOC) efferents (which innervate OHCs) inhibit AN initial peak (ANIP) responses from mid-to-high-level clicks, but do not inhibit initial BM responses, suggests a coupling of OHC motility to inner-hair-cell (IHC) stereocilia that is not through the BM. The main thesis objective was to test whether different OHC mechanisms produce AN responses to low-level sounds versus ANIP from mid-to-high-level clicks by comparing the suppressive effects of low-frequency "bias-tones" on these responses. Bias tones suppress by pushing OHC stereocilia into low-slope regions of their mechanoelectric transduction functions thereby lowering OHC amplification, particularly for probe tones near an AN-fiber's characteristic frequency (CF). This suppression occurs at opposite bias-tone phases, with one suppression typically larger than the other. Bias-tone effects were measured on cat AN-fiber responses using 50 Hz bias tones. In the first thesis part, bias-tone suppressive effects on AN responses to low-level clicks and low-level CF-tones were found to be similar, as expected but never previously shown. Then, in the main thesis focus, bias-tone suppressions of AN responses to low-level clicks and ANIP responses were studied. Both responses were suppressed twice each bias-tone cycle, but their major suppressions were at opposite bias-tone phases, which indicates that both ANIP and low-level AN responses depend on the slope of OHCstereocilia mechanoelectric-transduction, but with some significant difference. In the last thesis part, bias-tone suppression effects on low-CF (<4 kHz) AN-fiber responses to low-level CF and off-CF (by >0.7 octaves) tones were studied. Previous work found differences in AN-response group delays between CF and off-CF frequency regions that might arise from two different IHC-drive mechanisms, and the objective was to test this hypothesis. Our results showed similar bias-tone effects in both regions. Overall, the results demonstrate differences and similarities in the OHC mechanisms that produce ANIP and traditional, low-level cochlear amplification, and the results are consistent with the ANIP drive coupling OHC motility to IHC stereocilia without going through BM motion.
by Hui S. Nam.
Ph.D.
26
Ferrence, Kimberly Diane. "Studying the effects of changing experimental parameters on the medial olivocochlear efferent fibers and outer hair cell activity by measurement of distortion product otoacoustic emissions." [Gainesville, Fla.] : University of Florida, 2006. http://purl.fcla.edu/fcla/etd/UFE0015383.
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27
Fleischer, Mario. "Mehrfeldmodellierung und Simulation der äußeren Haarsinneszelle der Cochlea." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-100717.
Full textAbstract:
Das Innenohr des Säugetieres ist ein hochspezialisiertes sensorisches System, das durch ein komplexes mechanisches Verhalten gekennzeichnet ist. Neben der komplizierten Morphometrie und Geometrie kommen auch dem richtungsabhängigen Materialverhalten eine wesentliche Bedeutung zu. Es zeigt sich, daß im Cortischen Organ mit der äußeren Haarsinneszelle ein Zelltyp vorliegt, der durch seine physikalischen Eigenschaften das Gesamtverhalten des Innenohres maßgeblich beeinflußt. Wie jede tierische Zelle weist die äußere Haarsinneszelle als biomechanisches System eine heterogene Mikrostruktur auf. Vom mechanischen Standpunkt aus gesehen, ist neben der mehrschichtigen basolateralen Zellwand jede Einzelzelle durch ein viskoses inneres Fluid (Zellplasma) und einen Zellkern (Nukleus) gekennzeichnet. Die resultierenden mechanischen Eigenschaften des Gesamtsystems ”äußere Haarsinneszelle” können durch Experimente und eine geeignete Modellierung determiniert werden.
In dieser Arbeit wird ein neuer Ansatz zur Bestimmung der viskoelastischen Materialeigenschaften der basolateralen Wand vorgestellt. Durch Anwendung einer effektiven Fluid-Struktur-Interaktion wird das Gesamtsystem geschlossen untersucht und eine umfangreiche Materialparameterstudie durchgeführt. Dabei werden im Rahmen der Kontinuumsmechanik gültige Materialgesetze angewendet. Das durch partielle Differentialgleichungen formulierte mechanische Feldproblem wird im Rahmen der Finiten-Elemente-Methode approximiert, was zu einem linearen Gleichungssystem führt. Auf dieser Grundlage wird ein Finite-Elemente-Modell der äußeren Haarsinneszelle entwickelt. Die zur Beschreibung notwendigen Systemmatrizen – insbesondere die Dämpfungsmatrix – basieren dabei vollständig auf einem viskoelastischen Materialgesetz. Die benutzte Methodik läßt weiterhin eine effiziente Berechnung im Frequenzbereich zu.
Es zeigt sich, daß eine spezielle Dämpfungsformulierung die experimentell bestimmten dynamischen Eigenschaften der Zelle adäquat widerspiegelt. Eine Analyse auf Materialgesetzebene zeigt, daß dafür reine Schubdämpfung und damit eine spezielle Anisotropie im Viskositätstensor verantwortlich ist. Diese Eigenschaft bestimmt das dynamische Verhalten der äußeren Haarsinneszelle bis mindestens 10 kHz und liegt damit im Hörbereich.
Der Modellierung der Zelle geht eine angepaßte Auswertung der experimentell ermittelten Daten voraus. Die mechanisch geeignete Auswertung der zugrundeliegenden Experimente weist dabei auf mögliche Fehlerquellen bei der Analyse der Rohdaten hin. Das hat zur Konsequenz, daß der experimentellen Umgebung die gleiche Aufmerksamkeit geschenkt werden muß wie dem Meßobjekt selbst. Nur so kann eine geeignete Extraktion der für das Meßobjekt spezifischen Eigenschaften erfolgen.
28
Li, Zhiwei. "Membrane tether formation from outer hair cells with optical tweezers." Thesis, 2002. http://hdl.handle.net/1911/17521.
Full textAbstract:
The mechanical properties of the outer hair cells (OHCs) lateral wall are essential to elucidate the mechanism of OHC electromotility. Optical tweezers were used to characterize the mechanical properties of OHC plasma membrane (PM) by pulling tethers. A greater force was required for tether formations from OHC lateral wall (499 pN +/- 152) than from OHC basal end (142 pN +/- 49), consistent with the presence of a more extensive cytoskeleton support beneath the PM at the lateral wall. The apparent PM stiffness, which was estimated by measuring tether force at different tether length, was 3.71 pN/mum for OHC lateral wall and 4.57 pN/mum for OHC basal end. The apparent PM viscosity was measured by pulling tethers at different rates while continuously recording the tether force, and was estimated in the range of 13--33 pN·s/mum.
29
HUNG, CHUI CHEN, and 洪垂瑱. "Effects of L-Arginine and Taicatoxin on the Motility of Outer Hair Cells." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/63186034795561436164.
Full textAbstract:
碩士中山醫學大學
醫學研究所
91
Abstract The effect of L-arginine on the mammalian cochlear outer hair cell was studied in this experiment. L-arginine but not D-arginine or other amino acids (L-aspartate or L-glutamine) induced length increases of guinea pig outer hair cell. Similarity, a membrane permeable cyclic GMP analog, 8-(-4- chloro- phenylthio) guanosine 3’，5’-cyclic monophosphate (pCPT -cGMP) or 8-bromo-guanosine 3’，5’-cyclic monopho- sphate induced length increases of guinea pig outer hair cells. These length increases induced by L-arginine can be attenuated by a 30 min preincubation of the cells with the nitric oxide synthase inhibitors, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or 7-nitroindazole (7-NINA). Comparison on the elongate effect of cell length of L-arginine and ionomycin, L-arginine did not change the fluorescence intensity of fluo-3. Preincubation of the cells with EGTA (3 mM) for 40 min to reduce the extracellular calcium concentration did not influence the effect of L-arginine. The results demonstrated that nitric oxide/cGMP pathway involved in regulating the slow motility of mammalian outer hair cell can not be ruled out.In addition, the effect of L-arginine is independent of extracellular calcium concentration. Taicatoxin isolated from the venom of the Australian taipan snake (Oxyuranus scutellatus), has been previously regarded as a blockers of high threshold Ca2+ channels and small conductance Ca2+-activated K+ channels. Taicatoxin (0.19 mM) significantly prevented the cell shortening induced by high potassium (50 mM) medium. Similarly, cobaltous chloride, a nonselective calcium channel blocker, was to significantly reduced the effect of cell shortening induced by high potassium but not the effect of cell elongation induced by ionomycin. Other calcium channel blockers, nifedipine, w-conotoxin GVIA, w -agatoxin IVA did no such effect in prevented the cell length change induced by high potassium. Comparing the effects of taicatoxin and cobaltous chloride on the cell length and intracellular calcium change in outer hair cell, both taicatoxin and cobaltous chloride were able to prevent the cell shortening induced by high potassium but taicatoxin did not prevent the intracellular calcium increase induced by high calcium medium. The effect of taicatoxin was no relative with the membrane calcium channels or intracellular calcium concentration. In summary, the effects of L-arginine and taicatoxin were not relative with the calcium channels or cellular calcium concentration. Neither the action of L-arginine, nor taicatoxin were relative with the changes of calcium concentration or calcium channels. These findings support the hypothesis of calcium-independent slow motility of outer hair cells as described previously.
30
Stauffer, Eric Alan. "Mechanotransduction and adaptation in mammalian vestibular and auditory hair cells." 2008. http://proquest.umi.com/pqdweb?did=1805164991&sid=2&Fmt=2&clientId=3507&RQT=309&VName=PQD.
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Bendre, Ashish R. "A computer model of the cochlea using realizable feedback from motile outer hair cells." 1992. http://catalog.hathitrust.org/api/volumes/oclc/31746972.html.
Full textAbstract:
Thesis (M.S.)--University of Wisconsin--Madison, 1992.Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaf 66).
32
Buscone, S., Andrei N. Mardaryev, B. Raafs, J. W. Bikker, C. Sticht, N. Gretz, N. P. Farjo, N. E. Uzunbajakava, and Natalia V. Botchkareva. "A new path in defining light parameters for hair growth: discovery and modulation of photoreceptors in human hair follicle." 2017. http://hdl.handle.net/10454/12062.
Full textAbstract:
YesBackground and Objective: Though devices for hair growth based on low levels of light have shown encouraging results, further improvements of their efficacy is impeded by a lack of knowledge on the exact molecular targets that mediate physiological response in skin and hair follicle. The aim of this study was to investigate the expression of selected light-sensitive receptors in the human hair follicle and to study the impact of UV-free blue light on hair growth ex vivo. Material and Methods: The expression of Opsin receptors in human skin and hair follicles has been characterised using RT-qPCR and immunofluorescence approaches. The functional significance of Opsin 3 was assessed by silencing its expression in the hair follicle cells followed by a transcriptomic profiling. Proprietary LED-based devices emitting two discrete visible wavelengths were used to access the effects of selected optical parameters on hair growth ex vivo and outer root sheath cells in vitro. Results: The expression of OPN2 (Rhodopsin) and OPN3 (Panopsin, Encephalopsin) was detected in the distinct compartments of skin and anagen hair follicle. Treatment with 3.2 J/cm2 of blue light with 453 nm central wavelength significantly prolonged anagen phase in hair follicles ex vivo that was correlated with sustained proliferation in the light-treated samples. In contrast, hair follicle treatment with 3.2 J/cm2 of 689 nm light (red light) did not significantly affect hair growth ex vivo. Silencing of OPN3 in the hair follicle outer root sheath cells resulted in the altered expression of genes involved in the control of proliferation and apoptosis, and abrogated stimulatory effects of blue light (3.2 J/cm2; 453 nm) on proliferation in the outer root sheath cells. Conclusions: We provide the first evidence that 1) OPN2 and OPN3 are expressed in human hair follicle, and 2) 453 nm blue light at low radiant exposure exerts a positive effect on hair growth ex vivo, potentially via interaction with OPN3.
This study was supported by the European Marie-Curie Actions Programme, Grant agreement no.: 607886
33
"Biophysical Interactions of the OHC Motor Protein Prestin: A Study at the Single Molecule Level." Thesis, 2011. http://hdl.handle.net/1911/70287.
Full textAbstract:
The exquisite frequency selectivity and amplification characteristics of mammalian hearing intimately depend on the fast electromechanical motion of the outer hair cells in the cochlea. This membrane based process, termed electromotility, is driven by the protein prestin which is uniquely present in the OHC lateral wall. Voltage dependent motility, in OHCs and mammalian cells expressing prestin, is accompanied by intramembranous charge movement which is widely considered a signature of electromotility and prestin function. How prestin converts changes in membrane potential into axial length changes of OHCs is currently not understood at the molecular level. Many electromotility models predict that prestin conformational changes are the underlying mechanism connecting charge movement and motility. Currently, however, only indirect evidence for a prestin conformational change is available. Various experiments have indicated that the oligomeric states of prestin may be an important determinant of function. Numerous reports have provided varying estimates of prestin oligomeric state. However, estimates have been based on measurements performed outside the membrane making, firm biophysical conclusions difficult. Biophysical studies of prestin function have demonstrated its dependence on membrane properties. Alterations of membrane cholesterol affect voltage dependence of charge movement and motility. In addition cholesterol manipulations cause spatial redistribution of prestin and possibly change prestin oligomeric state. However, the underlying cause for prestin sensitivity to cholesterol and its relation to membrane distribution is unknown. We have applied single molecule fluorescence (SMF) imaging, single particle tracking (SPT), and Förster resonance energy transfer (FRET) to investigate prestin interactions at the molecular level. The results of our SMF experiments have suggested that prestin forms mainly tetramers and dimers in the cell membrane. Using SPT to map the trajectories of prestin in the membrane, we have found that prestin undergoes diffusion in and hops between membrane confinements of varying size. In addition, we have found that cholesterol affects the size and confinement strength of the compartments but does not affect the diffusivity within the compartments. Finally, using a combination of electrophysiology and FRET we have demonstrated that prestin undergoes voltage dependent structural changes. In total, our results refine our molecular understanding of prestin function.
34
Ya-Fang and 鄧雅方. "The study of the effect of Nitric Oxide on the Voltage-Dependant K＋Current of Outer Hair Cells in guinea pig cochlea." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/15754176458930854016.
Full textAbstract:
碩士中山醫學大學
醫學研究所
95
The purpose of the present investigation is to study the effect of NO and NO/cGMP pathway on the potassium current of outer hair cells. This study utilized isolated guinea-pig outer hair cells and the whole cell patch-clamp technique to determine whether NO and NO/cGMP signaling pathway involved in modulating the K+ channels of outer hair cells. The isolated outer hair cells were divided into seven groups as follows: group 1 treated with 3,4-diaminopyridine (3,4-DAP); group 2 with L-arginine (L-Arg); group 3 with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME); group 4 with S-niroso-N-acetylpenicillamine (SNAP); group 5 with diethylamine NONOate(DEA-NO); group 6 with dibutyryl cyclic guanosine 3’:5’ monophosphate and group 7 with KT5823. L-arginine, a nitric oxide precursor increased the amplitude of K+ current by 134.48% to the control at +60 mV holded. The NO donor S-niroso-N-acetylpenicillamine (SNAP) and diethylamine NONOate (DEA-NO) were also enhanced the current amplitude by 85.86 % and 103.37 % respectively. However, treated with PKG inhibitor (KT5823) and cGMP analogue (dbcGMP) did not significantly effect on the K+ current of outer hair cells. These results suggest that NO acting directly on the channel protein and increasing the K+ current amplitude without cGMP-PKG signaling pathway involved.
35
Lin, Kuang-Yi, and 林光義. "Theoretic analysis of effects on hearing curves by outer hair cell nonlinear capacitance." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/27821107622262248736.
Full textAbstract:
碩士國立清華大學
電機工程學系
101
Two mechanisms have been proposed for outer hair cells(OHCs) mediated amplification in mammalian cochlea : a hair-bundle(HB) motility generated during mechano-electrial transduction(MET) and a somatic motility generated by motor protein prestin in the outer hair cell lateral membrane. Both mechanisms are nonlinear. In the first section, this thesis uses computer models to simulate the outer hair cell fast effect by efferent control from medial olivocochlea interneuron. The middle-ear to inner ear and outer hair cell model proposed by Liu and Neely in 2009 and 2010 were adopted for this purpose. In the second section, with recent advance in molecular biology, the amount of prestin can be changed in all outer hair cells in the cochlea using novel knock-in techniques. This thesis simulated the effects on hearing curves with altered gene expression. The results of simulation in high frequency region of the cochlea are consistent with literature in that the outer hair cell nonlinear capacitance and somatic motility are not linearly correlated with the gain of the cochlea amplifier. Base on the computer model, insight regarding the cochlea frequency responses at low frequency region is also provided.
36
Organ, Louise E. "Investigating the lateral mobility of outer hair cell plasma membrane constituents by fluorescence recovery after photobleaching." Thesis, 2008. http://hdl.handle.net/1911/22165.
Full textAbstract:
Mammalian hearing exhibits exquisite sensitivity and frequency selectivity attributed to the unique properties of cochlear outer hair cells (OHCs). These sensory epithelial cells are electro-mechanical transducers, capable of converting sound-induced electrical signals into mechanical forces which provide feedback via a mechanism known as the cochlear amplifier. In a process aptly termed electromotility, electro-mechanical transduction manifests as whole-cell axial length changes in OHCs that occur in response to changes in the transmembrane potential. The polytopic motor protein prestin functions as the voltage sensor and molecular motor, both in OHCs and when expressed in heterologous systems. As the molecular mechanism(s) of electromotility remain unknown, examining the structure and function of prestin is a major focus of ongoing research.
Since changes in membrane composition and biophysical properties affect protein function and organization, we are particularly interested in membrane-protein interactions. Recent studies suggest that manipulations in membrane cholesterol levels reversibly shift the membrane microdomain distribution of prestin, modulate prestin oligomerization states, and alter prestin function, thus regulating electromotility through membrane-protein interactions. Measurements of protein and lipid lateral mobility provide a powerful tool to dynamically examine such interactions.
We hypothesize that OHC plasma membrane cholesterol levels affect electromotility either through microdomain-mediated mechanisms that cluster or segregate prestin molecules or via alterations in the material properties of the membrane, which in turn affect the resident proteins. Using fluorescence recovery after photobleaching (FRAP), we evaluated the lateral mobility of both protein and lipid components of the OHC. Then we showed that the diffusion of both prestin in HEK cells and lipids in OHCs is altered in response to changes in membrane cholesterol concentration. Cumulatively, this work demonstrates the complexity of prestin-membrane interactions and highlights the importance of their inclusion in current models of prestin function and electromotility.
37
Greeson, Jennifer N. "Investigating the role of the outer hair cell plasma membrane in electromotility and prestin function using quantitative optical microscopy techniques." Thesis, 2008. http://hdl.handle.net/1911/22210.
Full textAbstract:
Almost 25 years ago, the unique electromotile activity of mammalian outer hair cells (OHCs) was discovered. This cylindrical neuro-epithelial cell is capable of transducing changes in transmembrane potential into whole-cell axial deformations. The resulting contractions and elongations feedback into the sound-induced vibrations of the basilar membrane, enhancing hearing sensitivity and frequency detection capabilities. Although the complete mechanism of electromotility is not presently understood, the discovery and localization of the putative motor protein, prestin, to the OHC plasma membrane promotes the importance of the membrane in both OHC and cochlear behavior. A thorough understanding of the constituents of the OHC membrane, both lipids and proteins, as well as their interactions, is then crucial to current and future analyses of OHC function. In this work, we describe the use of quantitative optical microscopy to investigate protein-protein and membrane-protein interactions. For the former, we employ fluorescence resonance energy transfer (FRET) microscopy to assess prestin-prestin interactions in a heterologous expression system. For the latter, we have developed a specific implementation of fluorescence polarization microscopy (FPM) to measure the orientation of the fluorescent lipid analog di-8-ANEPPS in OHCs. Using both of these techniques, we can investigate the effects of treatments known to affect prestin function and non-linear capacitance in a membrane-dependent manner. The results undeniably highlight the importance of the plasma membrane in regulating prestin and OHC electromotile function.
38
Fleischer, Mario. "Mehrfeldmodellierung und Simulation der äußeren Haarsinneszelle der Cochlea." Doctoral thesis, 2011. https://tud.qucosa.de/id/qucosa%3A26314.
Full textAbstract:
Das Innenohr des Säugetieres ist ein hochspezialisiertes sensorisches System, das durch ein komplexes mechanisches Verhalten gekennzeichnet ist. Neben der komplizierten Morphometrie und Geometrie kommen auch dem richtungsabhängigen Materialverhalten eine wesentliche Bedeutung zu. Es zeigt sich, daß im Cortischen Organ mit der äußeren Haarsinneszelle ein Zelltyp vorliegt, der durch seine physikalischen Eigenschaften das Gesamtverhalten des Innenohres maßgeblich beeinflußt. Wie jede tierische Zelle weist die äußere Haarsinneszelle als biomechanisches System eine heterogene Mikrostruktur auf. Vom mechanischen Standpunkt aus gesehen, ist neben der mehrschichtigen basolateralen Zellwand jede Einzelzelle durch ein viskoses inneres Fluid (Zellplasma) und einen Zellkern (Nukleus) gekennzeichnet. Die resultierenden mechanischen Eigenschaften des Gesamtsystems ”äußere Haarsinneszelle” können durch Experimente und eine geeignete Modellierung determiniert werden.
In dieser Arbeit wird ein neuer Ansatz zur Bestimmung der viskoelastischen Materialeigenschaften der basolateralen Wand vorgestellt. Durch Anwendung einer effektiven Fluid-Struktur-Interaktion wird das Gesamtsystem geschlossen untersucht und eine umfangreiche Materialparameterstudie durchgeführt. Dabei werden im Rahmen der Kontinuumsmechanik gültige Materialgesetze angewendet. Das durch partielle Differentialgleichungen formulierte mechanische Feldproblem wird im Rahmen der Finiten-Elemente-Methode approximiert, was zu einem linearen Gleichungssystem führt. Auf dieser Grundlage wird ein Finite-Elemente-Modell der äußeren Haarsinneszelle entwickelt. Die zur Beschreibung notwendigen Systemmatrizen – insbesondere die Dämpfungsmatrix – basieren dabei vollständig auf einem viskoelastischen Materialgesetz. Die benutzte Methodik läßt weiterhin eine effiziente Berechnung im Frequenzbereich zu.
Es zeigt sich, daß eine spezielle Dämpfungsformulierung die experimentell bestimmten dynamischen Eigenschaften der Zelle adäquat widerspiegelt. Eine Analyse auf Materialgesetzebene zeigt, daß dafür reine Schubdämpfung und damit eine spezielle Anisotropie im Viskositätstensor verantwortlich ist. Diese Eigenschaft bestimmt das dynamische Verhalten der äußeren Haarsinneszelle bis mindestens 10 kHz und liegt damit im Hörbereich.
Der Modellierung der Zelle geht eine angepaßte Auswertung der experimentell ermittelten Daten voraus. Die mechanisch geeignete Auswertung der zugrundeliegenden Experimente weist dabei auf mögliche Fehlerquellen bei der Analyse der Rohdaten hin. Das hat zur Konsequenz, daß der experimentellen Umgebung die gleiche Aufmerksamkeit geschenkt werden muß wie dem Meßobjekt selbst. Nur so kann eine geeignete Extraktion der für das Meßobjekt spezifischen Eigenschaften erfolgen.