Dynamics of Intestinal Calcium Absorption in Neonates
| Autor: | Izumi Kaji |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
JCa2+
Ca2+ flux TRPV Cation Channels Weaning Development Calcium Channel Cav1.3 voltage-dependent L-type calcium channel alpha 1D subunit PCR polymerase chain reaction Intestine Small Humans Bone Original Research Calcium metabolism Pediatric KO knockout Hepatology Chemistry Dynamics (mechanics) Gastroenterology Infant Newborn μCT micro–computed tomography TAL thick ascending limb WT wild-type Trpv6 transient receptor potential vanilloid 6 Calcium Dietary PMCA1 plasma membrane Ca2+-ATPase 1 Intestinal Absorption Biophysics Calcium Calcium Channels HA hemagglutinin |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology |
| ISSN: | 2352-345X |
| Popis: | Background & Aims Intestinal Ca2+ absorption early in life is vital to achieving optimal bone mineralization. The molecular details of intestinal Ca2+ absorption have been defined in adults after peak bone mass is obtained, but they are largely unexplored during development. We sought to delineate the molecular details of transcellular Ca2+ absorption during this critical period. Methods Expression of small intestinal and renal calcium transport genes was assessed by using quantitative polymerase chain reaction. Net calcium flux across small intestinal segments was measured in Ussing chambers, including after pharmacologic inhibition or genetic manipulation of TRPV6 or Cav1.3 calcium channels. Femurs were analyzed by using micro–computed tomography and histology. Results Net TRPV6-mediated Ca2+ flux across the duodenum was absent in pre-weaned (P14) mice but present after weaning. In contrast, we found significant transcellular Ca2+ absorption in the jejunum at 2 weeks but not 2 months of age. Net jejunal Ca2+ absorption observed at P14 was not present in either Trpv6 mutant (D541A) mice or Cav1.3 knockout mice. We observed significant nifedipine-sensitive transcellular absorption across the ileum at P14 but not 2 months. Cav1.3 knockout pups exhibited delayed bone mineral accrual, compensatory nifedipine-insensitive Ca2+ absorption in the ileum, and increased expression of renal Ca2+ reabsorption mediators at P14. Moreover, weaning pups at 2 weeks reduced jejunal and ileal Cav1.3 expression. Conclusions We have detailed novel pathways contributing to transcellular Ca2+ transport across the distal small intestine of mice during development, highlighting the complexity of the multiple mechanisms involved in achieving a positive Ca2+ balance early in life. Graphical abstract |
| Databáze: | OpenAIRE |
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