Differences in electrogenic secretion of electrolytes in colonic epithelium of inbred mouse strains.

The mouse is the animal model of choice in studies of the physiology and pathophysiology of intestinal fluid and electrolyte transport. In the course of our research in colon physiology we have observed differences in electrical tissue properties and responses to agonists that induce electrogenic secretion of electrolytes among mice strains. Such differences are important enough to preclude comparisons between strains and might be crucial when choosing the genetic background for knockout of genes of interest. We have now investigated some of these differences by electrophysiological methods. Colonic tissue from Black Swiss, 129Sv and B6 mice were placed in Ussing chambers and their responses to a series of agonists and blockers recorded. We observe that while the 3 strains have similar anion secretory responses to increasing cAMP (around ‐100 μA cm −2 ), when the muscarinic agonist carbachol was used the largest response was seen with B6 tissue, compared to that of Black Swiss and 129Sv colon (‐200, ‐163 and ‐133 μA cm −2 respectively). The importance of the genetic background on the severity of cystic fibrosis in mice has long been known (Rozmahel et al., Nat Genet 12: 280‐7, 1996) and has been related to differences in calcium‐dependent anion secretion. We reported previously that basolateral KCNN4 calcium‐activated potassium channels are the rate‐limiting step in calcium‐agonist‐dependent anion secretion, rather than apical CFTR chloride channels (Flores et al., J Physiol 583: 705‐17, 2007). We are studying KCNN4 expression as a possible explanation to these differences. Supported by FONDECYT 3085023