ATP-ACTIVATED CHLORIDE PERMEABILITY IN BILIARY EPITHELIAL-CELLS IS REGULATED BY CALMODULIN-DEPENDENT PROTEIN-KINASE-II
MCGILL, J. M., YEN, M. S., BASAVAPPA, S., Mangel, A., & KWIATKOWSKI, A. P. (1995). ATP-ACTIVATED CHLORIDE PERMEABILITY IN BILIARY EPITHELIAL-CELLS IS REGULATED BY CALMODULIN-DEPENDENT PROTEIN-KINASE-II. Biochemical and Biophysical Research Communications, 208(2), 457-462.
Previous studies in freshly isolated rat biliary epithelial cells and in the human cholangiocarcinoma cell line Mz-ChA-1 have demonstrated that ATP activates a calcium-dependent chloride conductance. The coupling between the rise in intracellular calcium and activation of chloride channels has not previously been investigated. in the present study, we evaluated the potential role of calmodulin-dependent protein kinase II (CaMKII) in ATP-activated chloride permeability in Mz-ChA-1 cells. ATP stimulated [I-125] efflux, a marker for CI- movement. Peak efflux rates were inhibited by approximately 60% in cells pretreated with the calmodulin antagonist, W-7. In whole-cell patch clamp recordings, ATP and ionomycin activated calcium-dependent CI- currents. Pretreatment of cells with the CaMKII inhibitor KN-62 blocked activation by either 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.