Regulation of Alveolar Epithelial Na+ Channels by ERK1/2 in Chlorine-Breathing Mice

• DOI: 10.1165/rcmb.2011-0309oc
• Publication Date: 2011-10-14T04:34:40Z
• Authors: Ahmed Lazrak; Lan Chen; Asta Jurkuvenaite; Stephen F. Doran; Gang Liu; Qian Li; Jack R. Lancaster; Sadis Matalon
• Keywords: Male; Mitogen-Activated Protein Kinase 1; 0303 health sciences; Mitogen-Activated Protein Kinase 3; Patch-Clamp Techniques; Blotting, Western; Immunohistochemistry; Antioxidants; Membrane Potentials; Enzyme Activation; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Alveolar Epithelial Cells; Administration, Inhalation; Electric Impedance; Animals; Lipid Peroxidation; Chlorine; Phosphorylation; Epithelial Sodium Channels; Cells, Cultured

The mechanisms by which the exposure of mice to Cl(2) decreases vectorial Na(+) transport and fluid clearance across their distal lung spaces have not been elucidated. We examined biophysical, biochemical, physiological changes rodent epithelial channels (ENaCs) after Cl(2), identified involved. measured amiloride-sensitive short-circuit currents (I(amil)) isolated alveolar Type II (ATII) cell monolayers ENaC single-channel properties patching ATII ATI cells in situ. α-ENaC, γ-ENaC, total phosphorylated extracellular signal-related kinase (ERK)1/2, advanced products lipid peroxidation were Western blot analysis. Concentrations reactive intermediates assessed electron spin resonance (ESR). Amiloride-sensitive with conductances 4.5 18 pS evident situ air-breathing mice. At 1 hour 24 hours open probabilities these two decreased. This effect was prevented incubating slices inhibitors ERK1/2 or proteasomes lysosomes. increased concentrations intermediates, leading phosphorylation decreased I(amil) α-ENaC at exposure. administration antioxidants before activation, mitigated decrease concentrations. formed during activated vitro vivo, activity.