Segmental heterogeneity of basal and aldosterone-induced electrogenic Na transport in human colon

Recent in vitro studies in human colon have demonstrated marked segmental differences in electrogenic Na transport. In the present study, the Na channel blocker amiloride was used further to characterise basal and aldosterone-induced electrogenic Na transport in isolated human distal and proximal colon. Bathed in NaCl Ringer solution, distal and proximal colon exhibited similar basal electrical properties, but the amiloride-sensitive short-circuit current (I_sc) was 200% greater in the distal than in the proximal segment. Bathed in choline-Cl Ringer solution, totalI_sc decreased by 97% in distal colon and by 88% in proximal colon, indicating that Na dependent transport process(es) account almost entirely for theI_sc in both segments. Substituting Na₂SO₄ for NaCl Ringer solution (i) increased amiloride-sensitiveI_sc by 56% (p<0.01) in distal colon but had no effect on amiloride-sensitiveI_sc in proximal colon, and (ii) decreased amiloride-insensitiveI_sc in distal and proximal colon by 52% (p<0.05) and 81% (p<0.001) respectively. After the addition of nystatin to the apical membrane, the relationship between totalI_sc and mucosal Na concentration indicated that the activity of the basolateral membrane Na pump was similar in both colonic segments. In a further series of experiments, exposure of distal colon to 1 mol/l aldosterone for 5 h increased totalI_sc by 52% (p<0.05), which reflected stimulation of its amiloride-sensitive component; in contrast, aldosterone had no effect on proximal colon. These results indicate that Na-dependent electrogenic processes (with electrogenic Na transport predominant) are present throughout human colon, but there is marked segmental variability in the Na conductive properties of the apical membrane. Apical Na entry in distal colon occurs mainly through classical amiloride and aldosterone-sensitive Na channels. In contrast, the predominant apical Na entry mechanism in proximal colon is an amiloride and aldosterone-insensitive path-way.