Abstract
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 (ΔIsc) under open- and short-circuit conditions and simultaneously measured changes in unidirectional 22Na+ fluxes (ΔJNa) in Ussing chambers. Under short-circuit conditions, application of glucose resulted in an increase in ΔIsc and unidirectional mucosal to serosal 22Na+ (∆JNaMS) flux in both wild-type and cldn15−/− mice. However, under open-circuit conditions, ΔIsc was observed but ∆JNaMS 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 ∆JNaMS 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.
Highlights
Nutrient absorption in the small intestine is essential for assimilation of nutrients required for energy and growth
We previously showed that a loss of claudin-15 decreased the luminal Na+ concentration and glucose absorption is inhibited in mouse small intestine [14]
The results showed that under the short-circuit conditions in wild-type mice, luminal application of glucose resulted in an increase in ∆JNaMS which corresponded to the amplitude of ∆induced short-circuit current changes (Isc)
Summary
Nutrient absorption in the small intestine is essential for assimilation of nutrients required for energy and growth. This fluid is composed of 2 L from diet, 1 L of saliva, 2 L of gastric juice, 1 L of bile, 2 L of pancreatic juice, and 1 L of secretions from the small intestine, which contain only 0.8 moles of Na+ in total Another luminal Na+ providing mechanism would be via the paracellular pathway. To investigate whether paracellular Na+ conductance through claudin-15 is involved in this Na+ recycling system and to elucidate the role of Na+-nutrient cotransport induced luminal negativity for Na+ recycling, we measured glucose-induced short-circuit currents (∆Isc) under open- and short-circuit conditions in Ussing chambers. In cldn15−/− mice, a robust increase in ∆JNaMS was observed under open-circuit conditions, suggesting that the efficiency of Na+-recycling systems was reduced This phenomenon was mimicked by cholera toxin-induced diarrhea in wild-type mice.
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