Analysis of ClC-2 channels as an alternative pathway for chloride conduction in cystic fibrosis airway cells

• DOI: 10.1073/pnas.95.7.3879
• Publication Date: 2002-07-26T14:42:40Z
• Authors: Erik M. Schwiebert; Luis P. Cid-Soto; Diane Stafford; Mark Carter; Carol J. Blaisdell; Pamela L. Zeitlin; William B. Guggino; Garry R. Cutting
• Keywords: Chloride channel; Efflux; Channel blocker

Cystic fibrosis (CF) is a lethal inherited disease that results from abnormal chloride conduction in epithelial tissues. ClC-2 channels are expressed epithelia affected by CF and may provide key “alternative” target for pharmacotherapy of this disease. To explore possibility, the expression level was genetically manipulated airway cells derived cystic patient (IB3-1). Whole-cell patch-clamp analysis overexpressing identified hyperpolarization-activated Cl − currents (HACCs) displayed time- voltage-dependent activation, an inwardly rectifying steady-state current–voltage relationship. Reduction extracellular pH to 5.0 caused significant increases HACCs cells, appearance robust parental IB3-1 cells. stably transfected with antisense cDNA showed reduced compared Western blotting, reduction magnitude pH-dependent HACCs. determine whether changes alone could initiate transport via channels, we performed 36 efflux studies on endogenous ClC-2. Acidic increased rates both cell types, although had significantly greater longer duration than Compounds exploit mechanism activating pharmacologic option increasing conductance airways patients.