Na+-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na+ Recycling in Mouse Small Intestine
Na+-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na+ Recycling in Mouse Small Intestine
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DOI：
10.3390/ijms21020376
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发表时间：
2020-01-02
影响因子：
5.6
通讯作者：
Hayashi, Hisayoshi
中科院分区：
文献类型：
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作者：
Nakayama, Michiko;Ishizuka, Noriko;Hayashi, Hisayoshi
许多营养物质是通过Na+共转运系统吸收的，因此可以预测营养物质的吸收机制需要大量的管腔Na+。据认为，Na+通过细胞旁途径扩散回管腔，以支持Na+共转运吸收。然而，支持这种机制的直接实验证据尚未显示。为了阐明这一点，我们利用了claudin-15缺陷（cldn 15（-/-））小鼠，已被证明具有降低的细胞旁Na+渗透性。我们在开路和短路条件下测量了葡萄糖诱导的电流（Delta I-sc），同时测量了Ussing室中单向Na-22（+）通量（Delta J（Na））的变化。在短路条件下，在野生型和cldn 15（-/-）小鼠中，葡萄糖的应用导致Delta I-sc和单向粘膜至血清Na-22（+）（J（MS）（Na））通量的增加。然而，在开路条件下，观察到Delta I-sc，但J（MS）（Na）在野生型小鼠中受到强烈抑制，而在cldn 15（-/-）小鼠中则没有。此外，在用霍乱毒素处理的小鼠的十二指肠中，在开路条件下观察到细胞旁Na+电导降低和葡萄糖诱导的J（MS）（Na）增加。我们得出结论，Na+依赖性葡萄糖共转运吸收的Na+通过细胞旁Na+传导通过claudin-15再循环回到管腔，这是由Na+共转运诱导的管腔负性驱动的。
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 (Delta I-sc) under open- and short-circuit conditions and simultaneously measured changes in unidirectional Na-22(+) fluxes (Delta J(Na)) in Ussing chambers. Under short-circuit conditions, application of glucose resulted in an increase in Delta I-sc and unidirectional mucosal to serosal Na-22(+) (J(MS)(Na)) flux in both wild-type and cldn15(-/-) mice. However, under open-circuit conditions, Delta I-sc was observed but J(MS)(Na) 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(MS)(Na) 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.