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Calcium signaling in the cochlea – Molecular mechanisms and physiopathological implicationsKeywords: Hearing, Inner ear, Transducer adaptation, Ca2+ channels, Cadherin 23, Protocadherin 15, Plasma-membrane Ca2+-ATPase, Prestin, Intracellular stores, Calcium release, Mitochondria, Ribbon synapse, Adenosine-5'-triphosphate, Inositol 1,4,5-trisphosphate, Connexin 26, Connexin 30, Deafness, Mouse models Abstract: The cochlea is the snail–shaped inner ear structure where auditory processing is initiated. Different regions of the cochlear basilar membrane vibrate at different sinusoidal frequencies due to variations in membrane thickness and width from the base (high frequency) to the apex (low frequency) of the cochlea. The basilar membrane supports a polarized sensory epithelium, the organ of Corti, which is responsible for sound transduction; it has the form of an epithelial ridge encompassing highly specialized sensory inner hair cells (IHCs) and outer hair cells (OHCs) characterized by a mechanosensory organelle composed of a stereociliary bundle protruding from the endolymphatic (apical) pole [1] (for schematic drawings of cochlear structures and cellular components, see e.g. Ref. [2]). All cells providing mechanical support to hair cells are designated as supporting cells and, in the cochlea, these are flanked by epithelial cells. In the following, supporting and epithelial cells of the sensory epithelium will be collectively designated as cochlear non–sensory cells. In the mature organ of Corti, the supporting cells include inner phalangeal cells, inner and outer pillar cells, outer phalangeal cells (also known as Deiters’ cells), as well as Hensen’s, B?ttcher’s and Claudius’ cells. In the lateral direction from the organ of Corti, the epithelium comprises spiral prominence cells and marginal cells of the stria vascularis. Tight junctions between neighboring cells prevent diffusion of proteins between the apical and basolateral domain of hair cells and supporting cells, and insulate endolymph, the unusual extracellular fluid low in Na+ and Ca2+ but rich in K+ that bathes the apical pole of epithelium, from perilymph, the normal extracellular fluid the bathes the basolateral membrane of the cells. In adult wild-type rats, endolymph Ca2+ concentrations have been reported as 20–30 μM [3]. Although the detatils of endolymphatic Ca2+ development are not known, it has been r
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