Functional TRPV6 channels are crucial for transepithelial Ca2+ absorption
TRPV6 is considered the primary protein responsible for transcellular Ca2+ absorption. In vitro studies demonstrate that a negatively charged amino acid (D) within the putative pore region of mouse TRPV6 (position 541) is critical for Ca2+ permeation of the channel. To elucidate the role of TRPV6 in...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
01 Oct 2012
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| In: |
American journal of physiology. Gastrointestinal and liver physiology
Year: 2012, Volume: 303, Issue: 7, Pages: G879-G885 |
| ISSN: | 1522-1547 |
| DOI: | 10.1152/ajpgi.00089.2012 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1152/ajpgi.00089.2012 Verlag, Volltext: https://www.physiology.org/doi/full/10.1152/ajpgi.00089.2012 
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| Author Notes: | Titia E. Woudenberg-Vrenken, Anke L. Lameris, Petra Weißgerber, Jenny Olausson, Veit Flockerzi, René J. M. Bindels, Marc Freichel, and Joost G. J. Hoenderop |
| Summary: | TRPV6 is considered the primary protein responsible for transcellular Ca2+ absorption. In vitro studies demonstrate that a negatively charged amino acid (D) within the putative pore region of mouse TRPV6 (position 541) is critical for Ca2+ permeation of the channel. To elucidate the role of TRPV6 in transepithelial Ca2+ transport in vivo, we functionally analyzed a TRPV6D541A/D541A knockin mouse model. After weaning, mice were fed a regular (1% wt/wt) or Ca2+-deficient (0.02% wt/wt) diet and housed in metabolic cages. Blood was sampled for Ca2+ measurements, and the expression of Ca2+ transport proteins was analyzed in kidney and duodenum. Intestinal 45Ca2+ uptake was measured in vivo by an absorption assay. Challenging the mice with the Ca2+-deficient diet resulted in hypocalcemia in wild-type and TRPV6D541A/D541A mice. On a low-Ca2+ diet both mouse strains displayed increased expression of intestinal TRPV6, calbindin-D9K, and renal TRPV5. TRPV6D541A/D541A mice showed significantly impaired intestinal Ca2+ uptake compared with wild-type mice, and duodenal TRPV5 expression was increased in TRPV6D541A/D541A mice. On a normal diet, serum Ca2+ concentrations normalized in both mouse strains. Under these conditions, intestinal Ca2+ uptake was similar, and the expression levels of renal and intestinal Ca2+ transport proteins were not affected. We demonstrate that TRPV6D541A/D541A mice exhibit impaired transcellular Ca2+ absorption. Duodenal TRPV5 expression was increased in TRPV6D541A/D541A mice, albeit insufficient to correct for the diminished Ca2+ absorption. Under normal conditions, when passive Ca2+ transport is predominant, no differences between wild-type and TRPV6D541A/D541A mice were observed. Our results demonstrate a specific role for TRPV6 in transepithelial Ca2+ absorption. |
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| Item Description: | Gesehen am 15.10.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1522-1547 |
| DOI: | 10.1152/ajpgi.00089.2012 |