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Am J Physiol Gastrointest Liver Physiol 279: G463-G470, 2000;
0193-1857/00 $5.00
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Vol. 279, Issue 2, G463-G470, August 2000

EXPEDITED ARTICLE
Colon water transport in transgenic mice lacking aquaporin-4 water channels

Kasper S. Wang1, Tonghui Ma2, Ferda Filiz1, A. S. Verkman2, and J. Augusto Bastidas1

1 Department of Surgery, Stanford University School of Medicine, Stanford 94305-5408; and 2 Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521

Transgenic null mice were used to test the hypothesis that water channel aquaporin-4 (AQP4) is involved in colon water transport and fecal dehydration. AQP4 was immunolocalized to the basolateral membrane of colonic surface epithelium of wild-type (+/+) mice and was absent in AQP4 null (-/-) mice. The transepithelial osmotic water permeability coefficient (Pf) of in vivo perfused colon of +/+ mice, measured using the volume marker 14C-labeled polyethylene glycol, was 0.016 ± 0.002 cm/s. Pf of proximal colon was greater than that of distal colon (0.020 ± 0.004 vs. 0.009 ± 0.003 cm/s, P < 0.01). Pf was significantly lower in -/- mice when measured in full-length colon (0.009 ± 0.002 cm/s, P < 0.05) and proximal colon (0.013 ± 0.002 cm/s, P < 0.05) but not in distal colon. There was no difference in water content of cecal stool from +/+ vs. -/- mice (0.80 ± 0.01 vs. 0.81 ± 0.01), but there was a slightly higher water content in defecated stool from -/- mice (0.68 ± 0.01 vs. 0.65 ± 0.01, P < 0.05). Despite the differences in water permeability with AQP4 deletion, theophylline-induced secretion was not impaired (50 ± 9 vs. 51 ± 8 µl · min-1 · g-1). These results provide evidence that transcellular water transport through AQP4 water channels in colonic epithelium facilitates transepithelial osmotic water permeability but has little or no effect on colonic fluid secretion or fecal dehydration.

mercurial-insensitive water channel; water permeability; fecal dehydration


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