Na+ and Cl− movement across the intestinal epithelium occurs by several interconnected mechanisms:
(a) nutrient-coupled Na+ absorption,
(b) electroneutral NaCl absorption,
(c) electrogenic Cl− secretion by CFTR, and
(d ) electrogenic Na+ absorption by ENaC.
All these transport modes require a favorable electrochemical gradient maintained by the basolateral Na+/K+-ATPase, a Cl− channel, and K+ channels.
Electroneutral NaCl absorption is observed from the small intestine to the distal colon.
This transport is mediated by apical Na+/H+ (NHE2/3) and Cl−/HCO3 − (Slc26a3/a6 and others) exchangers that provide the major route of NaCl absorption.
Electroneutral NaCl absorption and Cl− secretion by CFTR are oppositely regulated by the autonomic nerve system, the immune system.
The mammalian intestine is responsible for the digestion and absorption of ingested food. However, the secretion and absorption of electrolytes and fluid are also essential functions of the intestine, in particular of intestinal epithelial cells. In humans, the gastrointestinal (GI) tract secretes 8–10 liters day−1 of fluid in the face of ingested food containing 1.5– 2 liters day−1 of fluid. Most fluid is (re)absorbed by the small intestine (∼95%) and large intestine (∼4%) of the GI tract. The small intestine secretes ∼1 liter day−1 and (re)absorbs ∼6.5 liters day−1, making it the major net fluid absorber. Because there is no active water movement in the human body, GI epithelial cells drive fluid movement through active movement of Na+ and Cl− (discussed in this review) or HCO3 − (beyond the scope of this review). In the intestine, there are four modes of Na+ and Cl− movement: (a) nutrient-coupled Na+ absorption, (b) electroneutral NaCl absorption, (c) electrogenic Cl− secretion by the cystic fibrosis transmembrane conductance regulator (CFTR), and (d ) electrogenic Na+ absorption by the epithelial Na+ channel (ENaC)
Nutrient-Coupled Na+ Absorption:
In the 1960s, transepithelial sugar and amino acid movement was measured using the shortcircuit current technique (the Ussing chamber). These studies found that absorption is dependent on extracellular (luminal) Na+.
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