The KCNE2 single transmembrane-spanning voltage-gated potassium (K) channel β subunit is ubiquitously expressed and essential for normal function of a variety of cell types, often regulation of the KCNQ1 K channel. A polymorphism upstream of is associated with reduced lung function in human populations, but the pulmonary consequences of gene disruption are unknown. Here, germline deletion of mouse reduced pulmonary expression of potassium channel α subunits and but did not alter expression of other genes. Kcne2 colocalized and coimmunoprecipitated with Kcnq1 in mouse lungs, suggesting the formation of pulmonary Kcnq1-Kcne2 potassium channel complexes. deletion reduced blood O, increased CO, increased pulmonary apoptosis, and increased inflammatory mediators TNF-α, IL-6, and leukocytes in bronchoalveolar lavage (BAL) fluids. Consistent with increased pulmonary vascular leakage, deletion increased plasma, BAL albumin, and the BAL:plasma albumin concentration ratio. mouse lungs exhibited baseline induction of the reperfusion injury salvage kinase pathway but were less able to respond this pathway to imposed pulmonary ischemia/reperfusion injury (IRI). We conclude that KCNE2 regulates KCNQ1 in the lungs and is required for normal lung function and resistance to pulmonary IRI. Our data support a causal relationship between gene disruption and lung dysfunction.-Zhou, L., Köhncke, C., Hu, Z., Roepke, T. K., Abbott, G. W. The KCNE2 potassium channel β subunit is required for normal lung function and resilience to ischemia and reperfusion injury.
Animals
Cytokines
Female
Gene Expression Regulation
Germ-Line Mutation
Inflammation
KCNQ1 Potassium Channel
Lung Injury
Mice
Mice, Knockout
Phosphorylation
Potassium Channels, Voltage-Gated
Reperfusion Injury
Shab Potassium Channels
