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Anatomy and Physiology of Balance
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
Nishchay Mehta, Andrew Forge, Jonathan Gale
The apical surface of a hair cell is covered by large, actin-rich, rod-like microvillar projections called stereocilia, grouped in a bundle (the ‘hair bundle’), wherein stereocilia progressively increase in length, like a staircase, with one large microtubule-based true cilium called the kinocilium positioned behind the longest row of stereocilia. The hair bundle staircase and position of the kinocilium define the axis of sensitivity or ‘polarity’ of the hair bundle (note the kinocilium, although present in early embryonic development, is absent in mature cochlear hair cell bundles). The tips of each shorter stereocilium is linked to the shaft of its neighbouring taller stereocilium by a thin proteinaceous filament, the tip link. Tip links are composed of two linear proteins joined end to end: cadherin 23 and protocadherin 15. Defects in one of these proteins are associated with different forms of Usher's syndrome. All of the hair cells in a crista are orientated in a single direction, along the plane of the semicircular duct, whereas hair cells in the maculae are arranged in a multiplanar orientation.
Physiology of Hearing
Published in James R. Tysome, Rahul G. Kanegaonkar, Hearing, 2015
In hair cells, physiological displacement of the stereocilia is caused by either a relative movement between the reticular lamina and the tectorial membrane (in the case of OHCs) or by the flow of endolymph over the cilia (in the case of IHCs). The mechanical gating of the transducer channels is thought to be controlled by tip-links, which connect the stereocilia. Transduction in hair cells is extremely fast and probably takes place at the tips of the stereocilia. If the stereocilia are stretched towards the tallest stereocilia, the probability of mechanically-gated channels opening increases; if they are stretched away from the tallest stereocilia, the probability of them closing increases. The transducer current is carried by K+ ions, the driving force for which is entirely electrical. (Note: The predominant cation in the endolymph is K+). The resting membrane potential of the hair cell (–60 mV), coupled with the large endolymphatic potential (~+80 mV), gives a total ionic gradient of 140 mV. The composition of the scala media’s endolymphatic fluid is largely controlled by the stria vascularis. A reduction in the magnitude of the endocochlear potential results in a loss of auditory thresholds that can mimic that seen in presbyacusis.
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
The cilia present on HAIR CELLS have tip links: that is, the tip of one hair cell is linked by a rather elastic filament to the cilia on either side of it. The point of contact is known as an INSERTIONAL PLAQUE, and it is from here that activation is generated. Tip links are important in regulating ion channel opening in the hair cells.
The involvement of liquid crystals in multichannel implanted neurostimulators, hearing and ENT infections, and cancer
Published in Acta Oto-Laryngologica, 2019
Chouard Claude-Henri, Christiane Binot, Jean-François Sadoc
The 150–200 nanometers tip-link is made up of PcDH15 and CDH23 cadherins inserting in the stereociliary membrane in the dense inferior and superior levels, respectively. Each end of the tip-link is thus anchored in the stereociliary membrane. Harmonin has PDZ domains which, in vitro, interact with PCDH15 and CDH23. Other domains CC: (colloid-colloid), PST: (proline serine threonine) are linked together by actin filaments. Myosin 1C motors maintain near-threshold tension within the system, facilitating mechano-sensory channel opening. In 2009 it seemed likely that harmonin organized different cytoplasmic components with CDH23 and the plasma membrane, optimizing mechano-sensory response to tension; it has since become clear that a cadherin-harmonin complex binds to PIP2. We hypothesize that a lipid raft is formed: [17] (VIH-1, protein Gag) and [18] (PI3K PIP2).
Hidden age-related hearing loss and hearing disorders: current knowledge and future directions
Published in Hearing, Balance and Communication, 2018
Richard Salvi, Dalian Ding, Haiyan Jiang, Guang-Di Chen, Antonio Greco, Senthilvelan Manohar, Wei Sun, Massimo Ralli
CBA/CaJ mice have been used extensively in studies of noise-induced hearing loss [29,47]; they also have been used to test for age-related deficits in the central auditory pathway [48,49]. C57BL/6J mice are also widely used in hearing research. This strain begins to develop progressive hearing loss and cochlear pathology around 5–6 months of age [19,46]. At 8 months of age, large OHC and IHC losses are evident in the high-frequency basal third of the cochlea (70–100% loss). At 26 months of age nearly, all the OHC are missing throughout the cochlea whereas the IHC lesion decreases from 100% loss at the high-frequency base of the cochlea to a 20% loss at the low-frequency apex. The growth of hair cell loss is consistent with progression of hearing loss [46]. This strain and its variants have been used to study the genetic [42] and biological variables [50,51] that contribute to ARHL and to evaluate therapies to slow the progression of ARHL [52]. A major genetic factor contributing to ARHL in C57BL/6J mice is a splice variant of the cadherin 23 gen on the ahl locus on Chromosome 10 t [53]. The cadherin 23 protein is a component of the tip links on hair cell stereocilia, which regulate the opening and closing of the transduction channels that control the influx of cations into the hair cells. A single nucleotide variant of the cadherin 23 gene, Cdh23c.753A, which is common to many inbred strains of mice, accelerates ARHL [54,55].
A novel missense mutation locus of cadherin 23 and the interaction of cadherin 23 and protocadherin 15 in a patient with usher syndrome
Published in Ophthalmic Genetics, 2020
Chuanzhen Zheng, Xinjun Ren, Dongjun Xing, Shaochong Bu, Dejia Wen, Ye He, Jinping Zhang, Lijie Dong, Xiaorong Li
To the best of our knowledge, there have been no reports regarding heterozygous mutations of CDH23 c.6155 C > T. Moreover, the variant of PCDH15 c.2367_2369delTGT observed in the present study was consistent with the findings by Zhan et al (6); however, the homozygous variant was only responsible for non-syndromic hearing loss (DFNB23). Previous investigations suggest that distinct USH proteins may interact to form USH multiprotein complexes that contribute to hearing impairment. Zheng et al (7) reported that mice doubly heterozygous for CDH23 v−2j and PCDH15av−3j mutations exhibited deafness and abnormal stereocilia in the outer and inner hair cells of the organ of Corti by 5 months of age, whereas single heterozygotes lacked this pathology. In addition, mutation screening for CDH23 and PCDH15 in 76 USH1 probands revealed two probands who had evidence of digenic inheritance of the USH phenotype involving doubly heterozygous mutations of CDH23 and PCDH15, all of which caused frameshifts resulting in truncated protein. Furthermore, it has been demonstrated that cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells (8,9). Moreover, it has been showed that protacadherin-15-containing links control the development and maintenance of the calyceal processes of photoreceptor cells in animal experiment (10). This is similar to the results of our study, subjects with doubly heterozygous variants of CDH23 c.6155 C > T and PCDH15 c.2367_2369delTGT exhibited congenital sensorineural deafness and progressive RP, whereas single heterozygotes lacked this pathology. This finding suggests the possibility that interaction of CDH23 and PCDH15 also in RPE cells and photoreceptors, which further highlights the functional integration of CDH23 and PCDH15; further studies of the molecular links, proteins, and pathways of the CDH23 and PCDH15 complex may improve understanding of the underlying pathogenesis. Furthermore, in contrast to the acknowledged autosomal recessive homozygous inheritance model of USH, we suspect that digenic heterozygous inheritance maybe an uncommon inheritance model of USH.