ATP-ACTIVATED CHLORIDE PERMEABILITY IN BILIARY EPITHELIAL-CELLS IS REGULATED BY CALMODULIN-DEPENDENT PROTEIN-KINASE-II

Previous studies in freshly isolated rat biliary epithelial cells and in the human cholangiocarcinoma cell line Mz-ChA-1 have demonstrated t hat ATP activates a calcium-dependent chloride conductance. The coupli ng between the rise in intracellular calcium and activation of chlorid e channels has not previously been investigated. in the present study, we evaluated the potential role of calmodulin-dependent protein kinas e II (CaMKII) in ATP-activated chloride permeability in Mz-ChA-1 cells . ATP stimulated [I-125] efflux, a marker for CI- movement. Peak efflu x rates were inhibited by approximately 60% in cells pretreated with t he calmodulin antagonist, W-7. In whole-cell patch clamp recordings, A TP and ionomycin activated calcium-dependent CI- currents. Pretreatmen t of cells with the CaMKII inhibitor KN-62 blocked activation by eithe r agent. It is concluded that calcium-dependent activation of chloride currents in Mz-ChA-1 cells is coupled to a CaMKII-dependent process. (C) 1995 Academic Press.