Lack of pendrin HCO^sub 3^-transport elevates vestibular endolymphatic [Ca^sup 2+^] by inhibition of acid-sensitive TRPV5 and TRPV6 channels

The low Ca... concentration ([Ca...]) of mammalian endolymph in the inner ear is required for normal hearing and balance. We reported (Yamauchi et al., Biochem Biophys Res Commun 331: 1353-1357, 2005) that the epithelial Ca... channels TRPVS and TRPV6 (transient receptor potential types 5 and 6) are...

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Published inAmerican journal of physiology. Renal physiology Vol. 292; no. 5; p. F1314
Main Authors Nakaya, Kazuhiro, Harbidge, Donald G, Wangemann, Philine, Schultz, Bruce D
Format Journal Article
LanguageEnglish
Published Bethesda American Physiological Society 01.05.2007
Subjects
Anatomy & physiology
Body fluids
Cell culture
Cell growth
Gene expression
Kidneys
Proteins
Rodents
Vitamin D
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Summary:The low Ca... concentration ([Ca...]) of mammalian endolymph in the inner ear is required for normal hearing and balance. We reported (Yamauchi et al., Biochem Biophys Res Commun 331: 1353-1357, 2005) that the epithelial Ca... channels TRPVS and TRPV6 (transient receptor potential types 5 and 6) are expressed in the vestibular system and that TRPV5 expression is stimulated by 1 ,25-dihydroxyvitamin D..., as also reported in kidney. TRPV5/6 channels are known to be inhibited by extracellular acidic pH. Endolymphatic pH, [Ca...], and transepithelial potential of the utricle were measured in Cl-/HCO3 exchanger pendrin (SLC26A4) knockout mice in vivo. Slc26a4... mice exhibit reduced pH and utricular endolymphatic potential and increased [Ca...]. Monolayers of primary cultures of rat semicircular canal duct cells were grown on permeable supports, and cellular uptake of ... was measured individually from the apical and basolateral sides. Net uptake of ... was greater after incubation with 1,25-dihydroxyvitamin D3. Net ... absorption was dramatically inhibited by low apical pH and was stimulated by apical alkaline pH. Gadolinium, lanthanum, and ruthenium red reduced apical uptake. These observations support the notion that one aspect of vestibular dysfunction in Pendred syndrome is a pathological elevation of endolymphatic [Ca...] due to luminal acidification and consequent inhibition of TRPVS/6-mediated Ca... absorption. (ProQuest-CSA LLC: ... denotes formulae/symbols omitted.)
ISSN:1931-857X
1522-1466