chapter  Chapter 6
9 Pages

Cholangiocyte Ion Channels:

Targets for Drug Development
WithJ. Gregory Fitz

Transepithelial transport of Cl ions contributes importantly to the formation of bile by cholangiocytes, the epithelial cells that line the lumen of intrahepatic bile ducts. This response is mediated in part by opening of Cl channels in the apical membrane. Recent emphasis has been placed on cAMP-regulated channels encoded by CFTR, the protein product of the cystic fibrosis gene. However, cholangiocytes also express Ca2+/calmodulin-regulated Cl channels as well as volume/PKCa-regulated Cl channels that each appear to be localized in part to the apical domain and capable of supporting transepithelial secretion. Moreover, there is emerging evidence to suggest that the transport capacity of the apical membrane can be shaped to meet rapidly changing physiologic demands through selective recruitment and retrieval of channel-containing vesicles. Consequendy, definition of the mechanisms that define the number, type and activity of Cl channels in the apical membrane may serve as a novel target for pharmacological agents that modify the volume and composition of bile through effects on duct cells.