The KCNE2 potassium channel β subunit is required for normal lung function and resilience to ischemia and reperfusion injury. Issue 9 (4th June 2019)

• Record Type: Journal Article
• Authors: Zhou, Leng; Köhncke, Clemens; Hu, Zhaoyang; Roepke, Torsten K.; Abbott, Geoffrey W.
• Is Part Of: FASEB journal. Volume 33:Issue 9(2019)
• Page Start: 9762
• Page End: 9774
• Publication Date: 2019-06-04
• Subjects: KCNQ1 -- MiRP1 -- pulmonary -- Kv channel -- epithelial; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201802519R
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: The KCNE2 single transmembrane–spanning voltage‐gated potassium (Kv ) channel β subunit is ubiquitously expressed and essential for normal function of a variety of cell types, often via regulation of the KCNQ1 Kv channel. A polymorphism upstream of KCNE2 is associated with reduced lung function in human populations, but the pulmonary consequences of KCNE2 gene disruption are unknown. Here, germline deletion of mouse Kcne2 reduced pulmonary expression of potassium channel α subunits Kcnq1 and Kcnb1 but did not alter expression of other Kcne genes. Kcne2 colocalized and coimmunoprecipitated with Kcnq1 in mouse lungs, suggesting the formation of pulmonary Kcnq1‐Kcne2 potassium channel complexes. Kcne2 deletion reduced blood O2, increased CO2, increased pulmonary apoptosis, and increased inflammatory mediators TNF‐α, IL‐6, and leukocytes in bronchoalveolar lavage (BAL) fluids. Consistent with increased pulmonary vascular leakage, Kcne 2 deletion increased plasma, BAL albumin, and the BAL:plasma albumin concentration ratio. Kcne2 −/− mouse lungs exhibited baseline induction of the reperfusion injury salvage kinase pathway but were less able to respond via 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 KCNE2 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. FASEB J. 33, 9762–9774 (2019). www.fasebj.org