Diarrhea in Ulcerative Colitis: The Role of Altered Colonic Sodium Transport

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Abstract
In normal human colon, water and sodium (Na+) absorption are directly related. Defective Na+ absorption may therefore be an important factor in the pathogenesis of diarrhea in ulcerative colitis (UC). Electrophysiological studies have revealed profound decreases in channel‐mediated apical Na+ entry and Na+‐K+‐ATPase‐mediated basolateral Na+ extrusion in surface epithelial cells in inflamed human distal colon. Recent molecular biological studies indicate that mucosal inflammation in UC leads to significant decreases in Na+ channel β‐ and γ‐subunit expression in the apical membrane of surface colonocytes, with a marked reduction in the levels of β‐ and γ‐subunit‐specific mRNAs. In addition, basolateral expression of the Na+‐K+‐ATPase α1‐isoform is reduced along the surface cellOcrypt cell axis in UC, although there is no change in the level of the corresponding mRNA. Diarrhea in ulcerative colitis is therefore related, at least in part, to a major defect in electrogenic Na+ absorption, which reflects changes in the levels of expression of critical subunits of both the apical Na+ channel and basolateral Na+‐K+‐ATPase.