Ion transport across the normal and CF neonatal murine intestine

Neonatal mice with cystic fibrosis (CF) exhibit a very high mortality due t o intestinal obstruction localized primarily to the ileum and colon. It has been hypothesized that lack of Cl- secretion and possibly elevated Na+ abs orption contribute to the gut problems in CF neonates. Therefore, intestine s (ileum, proximal colon, and distal colon) from normal and CF day-old mous e pups were studied on ultra-small-aperture (0.0135 cm(2)) Ussing chambers. All three regions of the normal neonatal intestine responded to forskolin with an increase in short-circuit current, which was completely absent in t he CF intestine. The neonatal distal colon exhibited a high rate of amilori de-sensitive electrogenic Na+ absorption, which did not differ between the normal and CF preparations. The ileum and proximal colon of both genotypes exhibited a small but significant electrogenic Na+ absorption. The neonatal proximal colon and ileum also exhibited electrogenic Na+-glucose cotranspo rt, which was significantly greater in the normal compared with the CF ileu m. In addition, all three intestinal regions exhibited electrogenic Na+-ala nine cotransport, which was significantly reduced in two of the regions of the CF neonatal intestine. It is speculated that: 1) the reduced rate of Na +-nutrient cotransport in the CF intestine contributes to the lower rate of growth in CF pups, whereas 2) the elevated electrogenic Na+ absorption in the neonatal intestine, coupled with an inability to secrete Cl-, contribut es to the intestinal obstruction in the CF pups.