Altered Na+ and Cl- flux during diet-induced mixed gallstone formation in the prairie dog

Recent studies suggest that altered gallbladder absorptive function may be an important and previously unrecognized factor in the pathogenesis of experimentally induced gallstones. The present study was designed to define the specific changes in gallbladder epithelial ion transport that occur during mixed gallstone formation. Fifteen prairie dogs were fed either control or corn-alfalfa chow for six months. No control animals developed gallstones or crystals. Three of eight corn-alfalfa-fed animals had large black stones, and the remaining five had crystals ("pregallstone" group). Corn-alfalfa-fed animals had significant increases in gallbladder bile cholesterol, phospholipids, and calcium as compared to controls. Gallbladders were removed and mounted in a Ussing chamber for electrophysiologic and ion flux studies. Gallbladders from animals fed corn-alfalfa demonstrated significant decreases in short-circuit current and potential difference as compared to controls (P less than 0.05). 22Na and 36Cl were used to determine unidirectional ion fluxes. While net ion fluxes were similar in pregallstone animals and controls, stone-forming animals exhibited a significant decrease in net Na+ flux and a significant reversal in the direction of net Cl- flux (from secretion to absorption) as compared to controls (P less than 0.05). These data indicate that mixed gallstone formation is associated with alterations in gallbladder ion transport. The role of these changes in the pathogenesis of mixed gallstones remains to be determined.