Converting gallbladder absorption to secretion: the role of intracellular calcium.

Abstract

Experimental cholelithiasis is associated with elevated biliary calcium concentration and altered gallbladder absorption. Recent studies showed that extracellular calcium ([Ca2+]ec) plays a role in regulating gallbladder ion transport. The extent to which intracellular calcium ([Ca2+]ic) mediates the changes in gallbladder ion transport is not clear. We hypothesize that [Ca2+]ic is an important regulator of gallbladder ion transport. Prairie dog gallbladders were mounted in Ussing chambers, standard electrophysiologic parameters were recorded, and unidirectional Na+, Cl- and H2O fluxes were measured before and after mucosal exposure of 10-5 mol/L calcium ionophore A23187 was performed. A23187 caused an increase in transepithelial short-circuit current and potential difference and a decrease in transepithelial resistance. A23187 inhibited mucosa to serosa Cl- flux and stimulated serosa to mucosa Na+ flux, resulting in increased net Cl- secretion and decreased net Na+ absorption. A23187 converted H2O from absorption to secretion. Transepithelial short-circuit current effect of A23187 was delayed by indomethacin pretreatment and was completely blunted by low bathing Ca2+. This is the first demonstration that increased [Ca2+]ic converts the gallbladder from its normal absorptive state to a secretory one. Furthermore [Ca2+]ic appears to regulate ion transport through mechanisms that are partially prostaglandin-dependent. Studies are necessitated to define possible links between gallbladder secretion of Cl- and H2O and mucus hypersecretion, a well-described phenomenon associated with cholesterol gallstone formation.