CELLULAR MECHANISMS OF Na+ ABSORPTION (GI Tract)

 1. Electrogenic Sodium Absorption

This is an active sodium absorption mechanism present not only in the intestine but also in several other epithelia. Active absorption of sodium creates a negative electrical potential in the compartment which sodium leaves as compared to the one which it enters. In case of the intestinal epithelium, the pump for active absorption is present in the basolateral membrane.

The process may be conceptually broken into two stages:

The process may be broken into two steps: 1 and 2. To understand the process, 2 may be considered before 1. Sodium is actively pumped across the basolateral membrane of intestinal epithelium (2). Since sodium ions are positively charged, it creates a potential difference across the membrane, the outside being positive as compared to inside the cell. As a result of the electrical gradient, sodium ions move passively from the lumen into the enterocyte (1). Active transport (2) is against the electrical and concentration gradient. The electrical gradient generated by the active transport (and hence the name electrogenic) leads to passive transport (1) along the electrical and concentration gradient

2. Non-electrolyte Coupled Sodium Transport

Glucose- and amino acid–coupled Na+ absorption occurs only in villous epithelial cells and not in crypt epithelial cells. This process is the primary mechanism for Na+ absorption after a meal, but it makes little contribution during the inter-digestive period, when only limited amounts of glucose and amino acids are present in the intestinal lumen
The Na/glucose cotransporter SGLT1 is responsible for glucose uptake across the apical membrane. Since the sodium concentration in the enterocyte is lower than in the lumen, this transport is along the concentration gradient. But the intracellular concentration being lower than the interstitial fluid concentration, the next step, i.e. transport across the basolateral membrane is active. The active transport mechanism, or the sodium pump, in the basolateral membrane is energised by ATP. As sodium is transported into the interstitial fluid, water and glucose get dragged along passively. Several distinct Na/amino acid Cotransporters, each specific for a different class of amino acids, are responsible for the Na+-coupled uptake of amino acids across the apical membrane
The glucose- and amino acid–coupled uptake of Na+ entry across the apical membrane increases intracellular [Na+], which, in turn, increases Na+ extrusion across the basolateral membrane through the Na-K pump
Because the apical Na/glucose and Na/amino acid cotransporters are electrogenic, as is the Na-K pump, the overall transport of Na+ carries net charge and makes VTE more lumen negative, As discussed later, the increase in the lumen negative VTE provides the driving force for the parallel absorption of Cl−
Nutrient-coupled Na+ transporters, unlike other small intestinal Na+ absorptive mechanisms, are not inhibited by either cAMP or [Ca2+]i . Thus, agonists that increase [cAMP]i (i.e., Escherichia coli or cholera enterotoxin) or [Ca2+]i (i.e., serotonin) do not inhibit glucose- or amino acid–stimulated Na+ absorption

3. Electroneutral NaCl absorption

Electroneutral NaCl absorption is not the result of a Na/Cl cotransporter, but rather of parallel apical membrane Na-H and Cl-HCO₃ exchangers that are closely linked by small changes in pH. Therefore the transport does not lead to generation of any transmembrane potential difference. In the human colon, DRA (downregulated-in-adenoma; SLC26A3) mediates this Cl-HCO 3 exchange. This mechanism of NaCl absorption is the primary method of Na⁺ absorption between meals (i.e., the inter-digestive period), but it does not contribute greatly to postprandial Na⁺ absorption, which is mediated primarily by the nutrient-coupled transporters described previously. It is not affected by either luminal glucose or luminal HCO₃⁻. However, aldosterone inhibits electroneutral NaCl absorption

The overall electroneutral NaCl absorptive process is regulated by both cAMP and cGMP, as well as by intracellular Ca²⁺. Increases in each of these three intracellular messengers reduce NaCl absorption. Conversely, decreases in [Ca²⁺]_i increase NaCl absorption. Decreased NaCl absorption is important in the pathogenesis of most diarrheal disorders. For example, one of the common causes of traveler’s diarrhea is the heat-labile enterotoxin produced by the bacterium E. coli. This toxin activates adenylyl cyclase and increases [cAMP]_i , which, in turn, decreases NaCl absorption and stimulates active Cl⁻. This toxin does not affect glucose-stimulated Na⁺ absorption

4. Electroneutral Na-H exchange

Luminal HCO₃⁻the result of pancreatic, biliary, and duodenal secretion—increases Na⁺ absorption in the proximal portion of the small intestine by stimulating apical membrane Na-H exchange. The Na-H exchanger couples Na⁺ uptake across the apical membrane to proton (H⁺) extrusion into the intestinal lumen, a process that is enhanced by both decreases in intracellular pH (pH_i) and increases in luminal pH (HCO₃⁻). The energy for Na-H exchange comes from the Na⁺ gradient, a consequence of the ability of the Na-K pump to extrude Na⁺, thereby lowering [Na⁺]_i. This process is characteristically inhibited by millimolar concentrations of the diuretic Amiloride