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Publication : Na<sup>+</sup>-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na<sup>+</sup> Recycling in Mouse Small Intestine.

First Author  Nakayama M Year  2020
Journal  Int J Mol Sci Volume  21
Issue  2 PubMed ID  31936130
Mgi Jnum  J:296569 Mgi Id  MGI:6467912
Doi  10.3390/ijms21020376 Citation  Nakayama M, et al. (2020) Na(+)-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na(+) Recycling in Mouse Small Intestine. Int J Mol Sci 21(2):376
abstractText  Many nutrients are absorbed via Na(+) cotransport systems, and therefore it is predicted that nutrient absorption mechanisms require a large amount of luminal Na(+). It is thought that Na(+) diffuses back into the lumen via paracellular pathways to support Na(+) cotransport absorption. However, direct experimental evidence in support of this mechanism has not been shown. To elucidate this, we took advantage of claudin-15 deficient (cldn15(-/-)) mice, which have been shown to have decreased paracellular Na(+) permeability. We measured glucose-induced currents (DeltaIsc) under open- and short-circuit conditions and simultaneously measured changes in unidirectional (22)Na(+) fluxes (DeltaJ(Na)) in Ussing chambers. Under short-circuit conditions, application of glucose resulted in an increase in DeltaIsc and unidirectional mucosal to serosal (22)Na(+) (J(Na)MS) flux in both wild-type and cldn15(-/-) mice. However, under open-circuit conditions, DeltaIsc was observed but J(Na)MS was strongly inhibited in wild-type but not in cldn15(-/-) mice. In addition, in the duodenum of mice treated with cholera toxin, paracellular Na(+) conductance was decreased and glucose-induced J(Na)MS increment was observed under open-circuit conditions. We concluded that the Na(+) which is absorbed by Na(+)-dependent glucose cotransport is recycled back into the lumen via paracellular Na(+) conductance through claudin-15, which is driven by Na(+) cotransport induced luminal negativity.
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