title: Inward Rectifier K+ Currents Are Regulated by CaMKII in Endothelial Cells of Primarily Cultured Bovine Pulmonary Arteries.
abstract: Endothelium lines the interior surface of vascular walls and regulates vascular tones. The endothelial cells sense and respond to chemical and mechanical stimuli in the circulation, and couple the stimulus signals to vascular smooth muscles, in which inward rectifier K+ currents (Kir) play an important role. Here we applied several complementary strategies to determine the Kir subunit in primarily cultured pulmonary arterial endothelial cells (PAECs) that was regulated by the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). In whole-cell voltage clamp, the Kir currents were sensitive to micromolar concentrations of extracellular Ba2+. In excised inside-out patches, an inward rectifier K+ current was observed with single-channel conductance 32.43 ± 0.45 pS and Popen 0.27 ± 0.04, which were consistent with known unitary conductance of Kir 2.1. RT-PCR and western blot results showed that expression of Kir 2.1 was significantly stronger than that of other subtypes in PAECs. Pharmacological analysis of the Kir currents demonstrated that insensitivity to intracellular ATP, pinacidil, glibenclamide, pH, GDP-β-S and choleratoxin suggested that currents weren't determined by KATP, Kir2.3, Kir2.4 and Kir3.x. The currents were strongly suppressed by exposure to CaMKII inhibitor W-7 and KN-62. The expression of Kir2.1 was inhibited by knocking down CaMKII. Consistently, vasodilation was suppressed by Ba2+, W-7 and KN-62 in isolated and perfused pulmonary arterial rings. These results suggest that the PAECs express an inward rectifier K+ current that is carried dominantly by Kir2.1, and this K+ channel appears to be targeted by CaMKII-dependent intracellular signaling systems.
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, Harbin Medical University-Daqing, Daqing 163319, Heilongjiang, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University-Daqing, Daqing 163319, Heilongjiang, China.|Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086, Heilongjiang, China.|Department of Biology, Georgia State University, 50 Decatur Street, Atlanta, Georgia, 30302, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, Harbin Medical University-Daqing, Daqing 163319, Heilongjiang, China.|Department of Rheumatology and Immunology, First Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biology, Georgia State University, 50 Decatur Street, Atlanta, Georgia, 30302, United States of America.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, Harbin Medical University-Daqing, Daqing 163319, Heilongjiang, China.
authors.forename: Qianlong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086, Heilongjiang, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086, Heilongjiang, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Biology, Georgia State University, 50 Decatur Street, Atlanta, Georgia, 30302, United States of America.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086, Heilongjiang, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Biology, Georgia State University, 50 Decatur Street, Atlanta, Georgia, 30302, United States of America.
authors.forename: Ningren
authors.initials: N
authors.lastname: Cui
authors.affiliation: Department of Biology, Georgia State University, 50 Decatur Street, Atlanta, Georgia, 30302, United States of America.
authors.forename: Chun
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086, Heilongjiang, China.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D011188:Potassium