Cl^- and K⁺ transport in human biliary cell lines

Background: The cellular mechanisms which contribute to billing secretion and absorption are not fully defined. The purpose of these studies was to evaluate the membrane ion transport properties of Mz-ChA-1 and Sk-ChA-1 cell lines derived from human biliary tumors. Methods: In cultured cells, ¹²⁵I and ³⁶Cl efflux rates were used to assess membrane anion permeability, and ⁸⁶Rb efflux rates were used to assess K⁺ permeability. Results: Sections of tumors grown on BALB/ Urd mice were used for morphological evaluation and for detection of cystic fibrosis transmembrane conductance regulator (CFTR), the protein product of the cystic fibrosis gene. There was organized development of ductular structures and cells stained for γ-glutamyl transpeptidase and CK-19. Immunoperoxidase staining for CFTR, which is likely a Cl^- channel, was also present. Increases in intracellular Ca²⁺ stimulated by exposure to ionomycin or thapsigargin increased efflux of ¹²⁵I, ^36Cl, and ⁸⁶Rb. Efflux of ¹²⁵I was greater than ³⁶Cl, and anion efflux was inhibited by the Cl^- channel blocker 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid. Increases in 5′-cyclic adenosine monophosphate increased efflux of ³⁶Cl greater than ¹²⁵I but had no effect on ⁸⁶Rb efflux. Both cell lines possess bumetanide-sensitive ⁸⁶Rb uptake consistent with possible Na⁺/K⁺/2Cl^- cotransport. Conclusions: These human cell lines retain certain phenotypic features of differentiated biliary cells and may be useful for further investigation of biliary fluid and electrolyte transport.