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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/F1314    most recent 00432.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Nakaya, K. Articles by Marcus, D. C. Search for Related Content PubMed PubMed Citation Articles by Nakaya, K. Articles by Marcus, D. C.

Lack of pendrin HCO₃^– transport elevates vestibular endolymphatic [Ca²⁺] by inhibition of acid-sensitive TRPV5 and TRPV6 channels

¹Cellular Biophysics Laboratory, ²Cell Physiology Laboratory, and ³Epithelial Cell Biology Laboratory, Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; ⁴Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan; ⁵Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland; and ⁶Renal Division, Emory University School of Medicine, Atlanta, Georgia

Submitted 30 October 2006 ; accepted in final form 29 December 2006

The low Ca²⁺ concentration ([Ca²⁺]) 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 Ca²⁺ channels TRPV5 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 D₃, as also reported in kidney. TRPV5/6 channels are known to be inhibited by extracellular acidic pH. Endolymphatic pH, [Ca²⁺], 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 [Ca²⁺]. Monolayers of primary cultures of rat semicircular canal duct cells were grown on permeable supports, and cellular uptake of ⁴⁵Ca²⁺ was measured individually from the apical and basolateral sides. Net uptake of ⁴⁵Ca²⁺ was greater after incubation with 1,25-dihydroxyvitamin D₃. Net ⁴⁵Ca²⁺ 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 [Ca²⁺] due to luminal acidification and consequent inhibition of TRPV5/6-mediated Ca²⁺ absorption.

epithelial calcium channel; vitamin D; SLC26a4; HCO₃^– secretion

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