Segmental segregation of Na/H Exchanger‐3 (NHE3) and Cl/HCO3 exchanger SLC26A3 (DRA) in rodent proximal colon

Abstract

The colon is believed to absorb NaCl through the coupled operation of the apical exchangers NHE3 and DRA. We determined the density of these proteins within the absorptive microdomain (apical margin of surface epithelial cells) by quantitative confocal immunofluorescence microscopy in colon segments from 5 mice and 4 rats fed a normal diet. Axial position was defined as the distance from the cecal/colon junction (0%) to the rectum (100%). In both rodents, NHE3 abundance was highest at 5–60% length, decreased steeply at 60–70% length, and was nearly absent at 70–100% length. In inverse fashion, DRA was absent at 0–20% length but increased steadily to maximal levels at ~60% length. The cecum contained abundant NHE3 and DRA in mouse, but only DRA in rat. The pH and [Na+] in the fluid overlying the colonic mucosa in fed anesthetized rats was measured using esophageal‐type microelectrodes. Surface pH profile correlated closely with positional variations in DRA abundance: pH was 7.6±0.2 in the cecum, decreased sharply in the proximal colon to 6.1±0.2, and returned to 7.5 by 60–100% length. Surface [Na+] was ~60 mM in the cecum, declined steadily to ~20 mM by 20% length, and declined further to ~10 mM over the rest of the colon. Our results indicate that NHE3 and DRA do not spatially co‐exist in the rodent proximal colon. Uncoupled operation of NHE3 without DRA could contribute to the luminal acidification distinctive of this segment.