ENHANCED COLONIC NA-FIBROSIS MICE VERSUS NORMAL MICE( ABSORPTION IN CYSTIC)

Because there are reports that electrogenic Na+ absorption is increase d in colonic epithelia of cystic fibrosis (CF) subjects, we tested whe ther amiloride-sensitive Na+ absorption was increased in the colonic e pithelia of CF mice compared with normal mice on high- or low-Na+ diet s. When mice consumed a diet high in Na+, none of the colonic regions (distal colon, proximal colon, or cecum) from either group of mice exh ibited an amiloride-sensitive short-circuit current (I-sc). However, w hen mice were placed on a low-Na+ diet for 2 wk, all three intestinal regions from the CF mice exhibited a significant response to amiloride (P less than or equal to 0.05). In contrast, normal mice on the low-N at diet exhibited an amiloride-sensitive I-sc that was smaller and onl y significant in the cecum and distal colon. Measurement of plasma ald osterone levels revealed that the CF mice on the low-Nai diet had sign ificantly greater aldosterone levels than similarly treated controls [ 8,906 +/- 1,039 (n = 14) vs. 5,243 +/- 1,410 pg/ml (n = 14), respectiv ely]. When mice were infused with a constant dose of aldosterone (1 mu g . g(-1). day(-1)) for 7 days, the distal colon of the CF mice still had a significantly greater amiloride-sensitive I-sc than did the nor mal distal colon. If the presence of CF transmembrane conductance regu lator (CFTR) downregulates Na+ absorption in the colonic tissue from n ormal mice, our data suggest that at least some CFTR may be colocalize d with the Nat channel. Alternatively, other factors may be involved.