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Epithelial calcium channel (TRPV5) regulates cochlear and vestibular calcium via vitamin D‐responsive pathway

The low luminal [Ca] in the inner ear is required for normal hearing and balance and we recently reported a TRPV5 channel‐based Ca transport system in primary cultures of semicircular canal (SCCD) [Yamauchi et al., BBRC, 2005]. The expression in inner ear was studied with quantitative RT‐PCR and Western blot. Tissue explants of rat stria vascularis (SV) and lateral wall (LW) from the cochlea and of SCCD were acutely cultured ± 1,25‐dihydroxyvitamin D3 (vitD). TRPV5 was present in all 3 tissues and upregulated in SCCD by vitD. TRPV6 expreession was low and unaffected by vitD. Calbindin‐D9k and ‐D28k were detected in all tissues and ‐D9k upregulated in SCCD and LW. Na/Ca‐exchangers (NCX‐1,‐2,‐3) were expressed in all tissues and NCX2 strongly upregulated in LW by vitD. PMCA‐1,‐3,‐4 were found in all tissues. PMCA4 was downregulated in SCCD and PMCA3 upregulated in LW by vitD. PMCA2 was not detected in SCCD and low in SV. The vitamin D receptor was detected in all tissues, with the highest expression in SCCD; expression levels were not affected by exposure to vitD. Western blots showed protein expression of TRPV5. These results demonstrate the expression of all components of the vitamin D‐responsive TRPV5 Ca absorptive pathway in both the cochlear and vestibular organs. The TRPV5 pathway is likely a major mechanism involved in calcium homeostasis and mutations in these genes or chemical interference would be expected to result in compromised hearing or balance. NIH grants R01‐DC00212 and P20‐RR017686.