Calcium gradients in inner ear endolymph

Salt, Alec N.; Inamura, Naoki; Thalmann, Ruediger; Vora, Arti

doi:10.1016/0196-0709(89)90030-6

Cited by 117 publications

(88 citation statements)

References 11 publications

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“…In the mammalian cochlea, which has been most studied, the endolymphatic cation concentrations are: K¤, 160 mÒ; Na¤ < 1 mÒ; Mg¥, 10 ìÒ; Ca¥, 20-40 ìÒ (Bosher & Warren, 1978;Bosher, 1979;Ikeda et al 1987;Salt et al 1989). Similar values have been measured in the auditory organs of reptiles like the turtle (Johnstone, Schmidt & Johnstone, 1963;Crawford et al 1991).…”

Section: Ca¥ Permeation and Blocksupporting

confidence: 59%

“…In the cochlea, the free Ca¥ has been measured as •30 ìÒ in mammals (Bosher & Warren, 1978;Ikeda, Kusakari, Takasaka & Saito, 1987;Salt, Inamura, Thalmann & Vorba, 1989) and 65 ìÒ in turtles (Crawford et al 1991). The significance of the endolymph composition is unclear, and the low Ca¥ is especially puzzling if Ca¥ entry is a crucial step in controlling transducer adaptation.…”

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confidence: 99%

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Calcium permeation of the turtle hair cell mechanotransducer channel and its relation to the composition of endolymph

Ricci

Fettiplace

1998

The Journal of Physiology

153

124

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Recordings of mechanoelectrical transducer currents were combined with calcium imaging of hair bundles in turtle auditory hair cells located near the high‐frequency end of the cochlea. The external face of the hair bundles was perfused with a range of Ca2+ concentrations to study the quantitative relationship between Ca2+ influx and transducer adaptation. With Na+ as the monovalent ion, the peak amplitude of the transducer current decreased monotonically as the external [Ca2+] was raised from 25 μM to 20 mM. When Na+ was replaced with the impermeant Tris the transducer current increased with external [Ca2+]. These results indicate that Ca2+ can both permeate and block the transducer channels. The Ca2+ concentration for half‐block of the monovalent current was 1 mM. To quantify the Ca2+ influx, the fraction of transducer current carried by Ca2+ was measured using the change in bundle fluorescence in cells loaded with 1 mM Calcium Green‐1. The fluorescence change was calibrated by substituting an impermeable monovalent ion to render Ca2+ the sole charge carrier. In the presence of Na+, the fractional Ca2+ current was ≈10 % in 50 μM Ca2+, a concentration similar to that in endolymph, which bathes the hair bundles in vivo. The amount of Ca2+ entering was dependent on the identity of the monovalent ion, and was larger with K+, suggesting that the transducer channel is a multi‐ion pore. Over a range of ionic conditions, the rate of transducer adaptation was proportional to Ca2+ influx indicating that adaptation is driven by a rise in intracellular [Ca2+]. Shifts in the current‐displacement function along the displacement axis in different external Ca2+ concentrations were predictable from variation in the resting Ca2+ influx. We suggest that changes in the resting open probability of the transducer channels adjust the entry of Ca2+ to keep its concentration constant at an internal site. The results demonstrate that endolymph containing high K+, 50 μM Ca2+ and low Mg2+ concentrations, maximizes the transducer current while still allowing sufficient Ca2+ entry to drive adaptation. The hair cell mechanotransducer channel, in its permeation and block by Ca2+, shows behaviour similar to the voltage‐gated Ca2+ channel and the cyclic nucleotide‐gated channel.

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Section: Ca¥ Permeation and Blocksupporting

confidence: 59%

mentioning

confidence: 99%

Calcium permeation of the turtle hair cell mechanotransducer channel and its relation to the composition of endolymph

Ricci

Fettiplace

1998

The Journal of Physiology

153

124

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“…Unlike Ca 2+ ions at the junction between EC1 and EC2, the N-terminal Ca 2+ ion is readily replaced with Eu, suggesting that it is bound with lower affinity. The Ca 2+ concentration could therefore significantly affect the formation and stability of adhesion complexes, especially in the endolymph that surrounds tip links, which has a comparatively low Ca 2+ concentration (20,21). The N-terminal Ca 2+ binding motif might under certain conditions only be partially occupied.…”

Section: +mentioning

confidence: 99%

Structure of the N terminus of cadherin 23 reveals a new adhesion mechanism for a subset of cadherin superfamily members

Elledge

Kaźmierczak

Clark³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The cadherin superfamily encodes more than 100 receptors with diverse functions in tissue development and homeostasis. Classical cadherins mediate adhesion by binding interactions that depend on their N-terminal extracellular cadherin (EC) domains, which swap Nterminal β-strands. Sequence alignments suggest that the strandswap binding mode is not commonly used by functionally divergent cadherins. Here, we have determined the structure of the EC1-EC2 domains of cadherin 23 (CDH23), which binds to protocadherin 15 (PCDH15) to form tip links of mechanosensory hair cells. Unlike classical cadherins, the CDH23 N terminus contains polar amino acids that bind Ca 2+ . The N terminus of PCDH15 also contains polar amino acids. Mutations in polar amino acids within EC1 of CDH23 and PCDH15 abolish interaction between the two cadherins. PCDH21 and PCDH24 contain similarly charged N termini, suggesting that a subset of cadherins share a common interaction mechanism that differs from the strand-swap binding mode of classical cadherins.T he organization of cells into tissues and organs depends on cadherin molecules that regulate such diverse processes as cell adhesion, synapse formation, and the development and function of sensory cells in the inner ear and retina (1-4). The defining feature of the cadherin superfamily is the extracellular cadherin (EC) domain, which occurs in varying repetitions in all cadherins. Based on sequence homology and domain structure, cadherins are divided into subfamilies including the classical cadherins, desmosomal cadherins, seven transmembrane cadherins, and protocadherins. Classical cadherins and desmosomal cadherins are the best-studied superfamily members and have well-documented roles in mediating cell adhesion and the formation of desmosomes, respectively (1-4). The function and adhesive properties of other cadherin superfamily members are less well studied.Crystallographic and biochemical studies have provided insights into the structure of cadherin extracellular domains and the mechanism that mediates adhesion between classical cadherins (5-13). The EC domain forms a protein module of the Ig-like fold consisting of seven β-strands that are arranged as two opposed β-sheets. The Nand C termini reside on opposite ends of the EC domain, facilitating the formation of tandem repeats. The connections between successive EC domains are rigidified by coordination of three Ca 2+ ions, which is mediated by amino acids that are conserved in all cadherins (5,9,14). Adhesion specificity resides in the EC1 domains. The crystallographic structures show that the adhesive binding interface is formed by "swapping" of the amino-terminal β-strands of opposite EC1 domains, whereby the strand of one monomer replaces the strand of the other. Critical for this interaction are the side chains of conserved Trp residues, which fit into hydrophobic pockets on the EC1 domain of the binding partner (5,8,10).Recent findings suggest that the formation of cadherin adhesion complexes is a multistep process, where cadherins ...

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“…While measurements of ionic composition have not been done in the embryonic/developing ear, young adult studies suggest that endolymph has concentrations of Ca 2+ (~20-100 μM) and sodium (<1 mM), considerably lower than that in the serum (Salt et al, 1989). This unique extracellular fluid is maintained by cells throughout the inner ear including the vestibular dark cells of the thin nonsensory epithelium of the utricle (Fermin et al, 1990;Hsu, 1991;Ichimiya et al, 1994), the stria vascularis (Kambayashi et al, 1982;Kusakari et al, 1978), the fibrocytes of the spiral ligament (Spicer and Schulte, 1991), and the endolymphatic sac and endolymphatic duct (Salt et al, 1989;Thalmann and Thalmann, 1999). Specialized tight junctions and interactions with a complex basement membrane are required to maintain the activities of these compartments.…”

Section: Establish the Ionic Environmentmentioning

confidence: 99%

Mixing model systems: Using zebrafish and mouse inner ear mutants and other organ systems to unravel the mystery of otoconial development

Hughes

Thalmann

et al. 2006

Brain Research

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Human vestibular dysfunction is an increasing clinical problem. Degeneration or displacement of otoconia is a significant etiology of age-related balance disorders and Benign Positional Vertigo (BPV). In addition, commonly used antibiotics, such as aminoglycoside antibiotics, can lead to disruption of otoconial structure and function. Despite such clinical significance, relatively little information has been compiled about the development and maintenance of otoconia in humans. Recent studies in model organisms and other mammalian organ systems have revealed some of the proteins and processes required for the normal biomineralization of otoconia and otoliths in the inner ear of vertebrates. Orchestration of extracellular biomineralization requires bringing together ionic and proteinaceous components in time and space. Coordination of these events requires the normal formation of the otocyst and sensory maculae, specific secretion and localization of extracellular matrix proteins, as well as tight regulation of the endolymph ionic environment. Disruption of any of these processes can lead to the formation of abnormally shaped, or ectopic, otoconia, or otoconial agenesis. We propose that normal generation of otoconia requires a complex temporal and spatial control of developmental and biochemical events. In this review, we suggest a new hypothetical model for normal otoconial and otolith formation based on matrix vesicle mineralization in bone which we believe to be supported by information from existing mutants, morphants, and biochemical studies.

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Calcium gradients in inner ear endolymph

Cited by 117 publications

References 11 publications

Calcium permeation of the turtle hair cell mechanotransducer channel and its relation to the composition of endolymph

Calcium permeation of the turtle hair cell mechanotransducer channel and its relation to the composition of endolymph

Structure of the N terminus of cadherin 23 reveals a new adhesion mechanism for a subset of cadherin superfamily members

Mixing model systems: Using zebrafish and mouse inner ear mutants and other organ systems to unravel the mystery of otoconial development

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