CONVERTING GALLBLADDER ABSORPTION TO SECRETION - THE ROLE OF INTRACELLULAR CALCIUM

Background. Experimental cholelithiasis is associated with elevated bi liary calcium concentration and altered gallbladder absorption. Recent studies showed that extracellular calcium ([Ca2+](ec)) plays a role i n regulating gallbladder ion transport. The extent to which intracellu lar calcium ([Ca2+](ic)) mediates the changes in gallbladder ion trans port is not clear We hypothesize that [Ca2+](ic), is an important regu lator of gallbladder ion transport. Methods. Prairie dog gallbladders were mounted in Ussing chambers, standard electrophysiologic parameter s were recorded, and unidirectional Na+, Cl-, and H2O fluxes were meas ured before and after mucosal exposure of 10(-5) mol/L calcium ionopho re A23187 was performed. Results. A23187 caused an increase in transep ithelial 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 a decreased net Na+ absorption. A23187 converted H2O from absorption to secretion. Transepithelial short-circuit curre nt effect of A23187 was delayed bg indomethacin pretreatment and was c ompletely blunted by low bathing Ca2+. Conclusions. 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 partiall y prostaglandin-dependent. Studies are necessitated to define possible links between gallbladder secretion of Cl- and H2O and mucus hypersec retion, a well-described phenomenon associated with cholesterol gallst one formation.