Premium
Claudin‐2 Confers Calcium Permeability to the Jejunum and Ileum in Early Life
Author(s) -
Beggs Megan R,
Plain Allen,
Lee Justin J,
Alexander R. Todd
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.575.16
Subject(s) - claudin , paracellular transport , ussing chamber , jejunum , ileum , transcellular , tight junction , intestinal permeability , calcium , small intestine , chemistry , calcium metabolism , medicine , endocrinology , permeability (electromagnetism) , biology , biochemistry , secretion , membrane
Infants and children must maintain a net positive calcium (Ca 2+ ) balance in order to achieve an optimal peak bone mineral density by early adulthood. Across the small intestine, Ca 2+ is absorbed via transcellular and paracellular pathways although the molecular details of these pathways in early life are not well delineated. Claudins are tight junction proteins that confer selective permeability to epithelia. Claudins‐2, −12 and −15 are expressed and have been implicated in paracellular Ca 2+ permeability across intestinal epithelia. To date, the functional contribution of these claudins to the Ca 2+ permeability (P Ca 2+ ) of small intestine segments has not been defined. The objective of this study was therefore to 1) determine if P Ca 2+ across small intestine segments changed with postnatal development 2) to asses whether claudin‐2 or −12 contribute P Ca 2+ to the small intestine. To this end, basolateral to apical 45 Ca 2+ fluxes on ex vivo intestinal segments in Ussing chambers were employed to indirectly assess permeability to Ca 2+ . We observed greater 45 Ca 2+ flux in P14 vs 2‐month mice across the duodenum (31.8 ± 2.2 vs 9.5 ± 2.0 nmol/h/cm 2 , P<0.0001) and jejunum (42.3 ± 3.9 vs 21.8 ± 3.5 nmol/h/cm 2 , P<0.01) but not ileum (40.5 ± 3.2 vs 30.1 ± 5.7 nmol/h/cm 2 , P=0.13). Next, we measured P Ca 2+ directly in Ussing chambers using diffusion potentials. P Ca 2+ was significantly greater in younger mice across the duodenum (1.43 ± 0.04 vs 1.13 ± 0.08 × 10 −4 cm/s, P<0.01), jejunum (1.64 ± 0.09 vs 0.84 ± 0.04 × 10 −4 cm/s, P<0.0001) and ileum (1.72 ± 0.08 vs 0.81 ± 0.05 × 10 −4 cm/s, P<0.0001). To determine if claudin‐2 or −12 facilitates greater P Ca 2+ at P14, diffusion potential experiments were repeated on Cldn2 or Cldn12 knockout (KO) mice. P Ca 2+ was decreased in Cldn2 KO mice at P14 across the jejunum (1.85 ± 0.09 vs 1.24 ± 0.07 × 10 −4 cm/s, P<0.0001) and ileum (1.92 ± 0.07 vs 1.09 ± 0.06 × 10 −4 cm/s, P<0.0001) to levels not different than 2‐month WT and KO mice. No differences were observed between Cldn12 knockout mice compared to wildtype littermates at either age. We conclude that the younger mice have enhanced Ca 2+ permeability along the small intestine relative to older animals. Further, the increased jejunal and ileal Ca 2+ permeability is mediated by claudin‐2 which likely contributes to a positive calcium balance for normal growth. Support or Funding Information This work was funded by grants from the Women and Children's Health Research Institute, which is supported by the Stollery Children's Hospital Foundation, and the National Sciences and Engineering Research Council to RTA, who is the Canada Research Chair in Renal Epithelial Transport Physiology. MRB is supported by a Vanier Canada Graduate Scholarship, and Alberta Innovates Clinician Fellowship. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .