| First Author | Rievaj J | Year | 2013 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 305 |
| Issue | 4 | Pages | G303-13 |
| PubMed ID | 23764894 | Mgi Jnum | J:205078 |
| Mgi Id | MGI:5543986 | Doi | 10.1152/ajpgi.00490.2012 |
| Citation | Rievaj J, et al. (2013) The Na(+)/H(+) exchanger isoform 3 is required for active paracellular and transcellular Ca(2)(+) transport across murine cecum. Am J Physiol Gastrointest Liver Physiol 305(4):G303-13 |
| abstractText | Intestinal calcium (Ca(2)(+)) absorption occurs via paracellular and transcellular pathways. Although the transcellular route has been extensively studied, mechanisms mediating paracellular absorption are largely unexplored. Unlike passive diffusion, secondarily active paracellular Ca(2)(+) uptake occurs against an electrochemical gradient with water flux providing the driving force. Water movement is dictated by concentration differences that are largely determined by Na(+) fluxes. Consequently, we hypothesized that Na(+) absorption mediates Ca(2)(+) flux. NHE3 is central to intestinal Na(+) absorption. NHE3 knockout mice (NHE3-/-) display impaired intestinal Na(+), water, and Ca(2)(+) absorption. However, the mechanism mediating this latter abnormality is not clear. To investigate this, we used Ussing chambers to measure net Ca(2)(+) absorption across different segments of wild-type mouse intestine. The cecum was the only segment with net Ca(2)(+) absorption. Quantitative RT-PCR measurements revealed cecal expression of all genes implicated in intestinal Ca(2)(+) absorption, including NHE3. We therefore employed this segment for further studies. Inhibition of NHE3 with 100 muM 5-(N-ethyl-N-isopropyl) amiloride decreased luminal-to-serosal and increased serosal-to-luminal Ca(2)(+) flux. NHE3-/- mice had a >60% decrease in luminal-to-serosal Ca(2)(+) flux. Ussing chambers experiments under altered voltage clamps (-25, 0, +25 mV) showed decreased transcellular and secondarily active paracellular Ca(2)(+) absorption in NHE3-/- mice relative to wild-type animals. Consistent with this, cecal Trpv6 expression was diminished in NHE3-/- mice. Together these results implicate NHE3 in intestinal Ca(2+) absorption and support the theory that this is, at least partially, due to the role of NHE3 in Na(+) and water absorption. |
