Na+-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na+ Recycling in Mouse Small Intestine

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.

Cldn-7 deficiency promotes experimental colitis and associated carcinogenesis by regulating intestinal epithelial integrity

“…TJ-related proteins affect intestinal permeability, the development of intestinal inflammation and CAC. [10][11][12][13][14][15][16][17] Claudins maintain the integrity of intestinal barrier and epithelial cell polarity, and regulate permeability. 18 Additionally, claudins may also act as signaling proteins involved in inflammation, cell proliferation and differentiation.…”

Twenty-Four-Hour Urinary Sodium Excretion Predicts Therapeutic Effectiveness of Oral Rehydration Saline in Pediatric Vasovagal Syncope

“…It has been supported by randomized controlled trials as well as meta-analysis that children with vasovagal syncope can benefit from the oral rehydration saline therapy, which can provide a quantified dosage of supplemental water and salt on the basis of the patients’ original diet [ 3 , 18 ]. In addition to the supplementary sodium chloride and fluid volume, other components of oral rehydration saline, such as glucose, can promote the absorption of sodium ions at the small intestine, which may enhance the efficacy of oral rehydration saline [ 24 , 25 ]. Therefore, looking for indicators that can reflect the decrease in blood volume to suggest the oral rehydration saline treatment to the vasovagal syncope patients with low circulating blood volume as the pathogenesis is interesting and potentially useful.…”

The effect of fasting on sodium-dependent glucose absorption in the mouse proximal small intestine

“…The dilution potential was measured under open-circuit conditions, and the transepithelial potential was determined by Ohm's law from the voltage change measured with an external current load of ± 20 µA every 5 minutes. To measure the dilution potential, the buffer on one side (either Mucosal or Serosal side) was replaced with the above normal Ringer's solution containing 60 mM NaCl and 120 mM mannitol as previously described [8] [19].…”

“…Thus, the existence and signi cance of the diffusional transport component in glucose transport is still being debated, and even now the results of previous studies cannot be fully explained. Furthermore, we have demonstrated that the Na + which is absorbed by Na + -glucose cotransport is recycled back into the lumen via paracellular Na + conductance through claudin-15, which is driven by Na + cotransport-induced luminal potential [19]. However, little research has been done on how fasting affects the ion permeability of the small intestinal tight junctions.…”