Electrogenic transport, oxygen consumption, and sensitivity to acute hypoxia of human colonic epithelium

Abstract

It is recognized that epithelial ion transport depends on oxygen supply, but this dependence has not been characterized in the human colon in vitro despite its surgical and clinical implications. The aim of this study is to measure the oxygen consumption of colonic epithelium under conditions which preserve vectorial ion transport and to assess the sensitivity of the human colonic epithelium short-circuit current (I (sc)) to acute hypoxia induced in vitro. Isolated mucosa preparations from human sigmoid colon were placed in a modified Ussing chamber which allows simultaneous measurement of short-circuit current (I (sc)) and oxygen consumption (QO(2)). In separate experiments, the sensitivity to acute hypoxia induced in a conventional Ussing chamber was assessed. Basal mean ± SEM values (n = 8) were I (sc) = 3.3 ± 0.5 μEq h(-1) cm(-2) and QO(2) = 8.09 ± 0.55 μmol h(-1) cm(-2). The contribution of the serosal side to the oxygen supply was higher than that of the mucosal side (p = 0.0023). Ouabain reduced I (sc) by 70% (P < 0.0001) and QO(2) by 26% (n = 8; P = 0.0009), suggesting that a large fraction of QO(2) is needed to support ouabain-sensitive electrogenic transport. Induction of hypoxia at both sides of the Ussing chamber caused a rapid decrease in I (sc) after 2 min. I (sc) was also significantly depressed when hypoxia was induced by 5 min in the serosal side (n = 6, P < 0.0001), but was unaffected by hypoxia induced in the mucosal side. The present results allow a better understanding of the clinical consequences of acute hypoxia on intestinal ion transport.