Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k.
To study the role of the epithelial calcium channel transient receptor potential vanilloid type 6 (TRPV6) and the calcium-binding protein calbindin-D9k in intestinal calcium absorption, TRPV6 knockout (KO), calbindin-D9k KO, and TRPV6/calbindin-D(9k) double-KO (DKO) mice were generated. TRPV6 KO, calbindin-D9k KO, and TRPV6/calbindin-D9k DKO mice have serum calcium levels similar to those of wild-type (WT) mice ( approximately 10 mg Ca2+/dl). In the TRPV6 KO and the DKO mice, however, there is a 1.8-fold increase in serum PTH levels (P < 0.05 compared with WT). Active intestinal calcium transport was measured using the everted gut sac method. Under low dietary calcium conditions there was a 4.1-, 2.9-, and 3.9-fold increase in calcium transport in the duodenum of WT, TRPV6 KO, and calbindin-D9k KO mice, respectively (n = 8-22 per group; P > 0.1, WT vs. calbindin-D9k KO, and P < 0.05, WT vs. TRPV6 KO on the low-calcium diet). Duodenal calcium transport was increased 2.1-fold in the TRPV6/calbindin-D9k DKO mice fed the low-calcium diet (P < 0.05, WT vs. DKO). Active calcium transport was not stimulated by low dietary calcium in the ileum of the WT or KO mice. 1,25-Dihydroxyvitamin D3 administration to vitamin D-deficient null mutant and WT mice also resulted in a significant increase in duodenal calcium transport (1.4- to 2.0-fold, P < 0.05 compared with vitamin D-deficient mice). This study provides evidence for the first time using null mutant mice that significant active intestinal calcium transport occurs in the absence of TRPV6 and calbindin-D9k, thus challenging the dogma that TRPV6 and calbindin-D9k are essential for vitamin D-induced active intestinal calcium transport.
Benn
Bryan S
BS
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School Newark, New Jersey 07103, USA.
Ajibade
Dare
D
Porta
Angela
A
Dhawan
Puneet
P
Hediger
Matthias
M
Peng
Ji-Bin
JB
Jiang
Yi
Y
Oh
Goo Taeg
GT
Jeung
Eui-Bae
EB
Lieben
Liesbet
L
Bouillon
Roger
R
Carmeliet
Geert
G
Christakos
Sylvia
S
D000818:Animals; D001693:Biological Transport, Active; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000172:deficiency* / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology; D007422:Intestines / Q000502:physiology*; D007668:Kidney / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064030:S100 Calcium Binding Protein G / Q000235:genetics*; D050916:TRPV Cation Channels / Q000172:deficiency* / Q000235:genetics
D064026:Calbindins; D015220:Calcium Channels; D064030:S100 Calcium Binding Protein G; C576507:S100g protein, mouse; D050916:TRPV Cation Channels; C446923:Trpv6 protein, mouse; D002118:Calcium