Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease

Abstract

The colonic epithelium has both absorptive and secretory functions. The transport is characterized by a net absorption of NaCl, short-chain fatty acids (SCFA), and water, allowing extrusion of a feces with very little water and salt content. In addition, the epithelium does secret mucus, bicarbonate, and KCl. Polarized distribution of transport proteins in both luminal and basolateral membranes enables efficient salt transport in both directions, probably even within an individual cell. Meanwhile, most of the participating transport proteins have been identified, and their function has been studied in detail. Absorption of NaCl is a rather steady process that is controlled by steroid hormones regulating the expression of epithelial Na+ channels (ENaC), the Na+-K+-ATPase, and additional modulating factors such as the serum- and glucocorticoid-regulated kinase SGK. Acute regulation of absorption may occur by a Na+ feedback mechanism and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl− secretion in the adult colon relies on luminal CFTR, which is a cAMP-regulated Cl− channel and a regulator of other transport proteins. As a consequence, mutations in CFTR result in both impaired Cl− secretion and enhanced Na+ absorption in the colon of cystic fibrosis (CF) patients. Ca2+- and cAMP-activated basolateral K+ channels support both secretion and absorption of electrolytes and work in concert with additional regulatory proteins, which determine their functional and pharmacological profile. Knowledge of the mechanisms of electrolyte transport in the colon enables the development of new strategies for the treatment of CF and secretory diarrhea. It will also lead to a better understanding of the pathophysiological events during inflammatory bowel disease and development of colonic carcinoma.

Intestinal Mineralocorticoid Receptor Contributes to Epithelial Sodium Channel–Mediated Intestinal Sodium Absorption and Blood Pressure Regulation

“…The reduction in β‐ and γ‐ENaC but not α‐ENaC expression in the colons of IEC‐MR‐KO mice was consistent with these previous findings. ENaC and NHE3 are thought to have major roles in sodium absorption in the intestine 34. NHE3 expression was ≈50% lower in IEC‐MR‐KO mice than in control mice.…”

Expression of hypoxia‐inducible, membrane‐bound carbonic anhydrase isozyme XII in mouse tissues

“…The enterocytes located in the epithelial cuff region are differ- entiated from the colonic crypt cells (Lipkin, 1985). The base crypt enterocytes show the highest proliferative activity, demonstrate limited expression of differentiation markers, and have a high chloride secretory activity (Kunzelmann and Mall, 2002). The most luminal epithelial cells, representing the mature enterocytes, have a lower tendency to proliferate, express several differentiation marker proteins and certain lectins, and have a primarily absorptive function.…”

“…The most luminal epithelial cells, representing the mature enterocytes, have a lower tendency to proliferate, express several differentiation marker proteins and certain lectins, and have a primarily absorptive function. The colonic absorption of NaCl can be electrogenic via epithelial Na ϩ channels or is electroneutral via parallel Na ϩ /H ϩ and Cl -/HCO 3 -exchange (Kunzelmann and Mall, 2002). From these two pathways, electroneutral NaCl absorption has been shown to take place in both crypts and surface epithelial cuff region.…”

Bile acids inhibit Na+/H+ exchanger and Cl−/HCO3 − exchanger activities via cellular energy breakdown and Ca2+ overload in human colonic crypts

“…The colonic epithelial cells express numerous ion channels, pumps and transporters located either on the luminal or the basolateral membrane, allowing highly efficient transport of water and ions, especially Na + and Cl - [25]. The adequate activity of these transporters is essential to keep the precise balance between absorption and secretion.…”