title: Hypoxia induces voltage-gated K+ (Kv) channel expression in pulmonary arterial smooth muscle cells through hypoxia-inducible factor-1 (HIF-1).
abstract: Hypoxia-inducible factor-1 (HIF-1) regulates the expression of hypoxia-inducible genes by binding erythropoietin (EPO) enhancer fragments. Of these genes, HIF-1 upregulates voltage-gated K+1.2 channels (Kv1.2) in rat PC12 cells. Whether HIF-1 regulates hypoxia-induced Kv channel expression in cultured pulmonary artery smooth muscle cells (PASMCs), however, has not been determined. In this study, we investigated the effects of hypoxia on the expression of Kv1.2 Kv1.5, Kv2.1, and Kv9.3 channels in PASMCs and examined the direct role of HIF-1 by transfecting either wild type or mutant EPO enhancer fragments. Our results showed that 18 h exposure to hypoxia significantly increased the expression of Kv1.2, Kv1.5, Kv2.1, and Kv9.3; and this hypoxia-induced upregulation was completely inhibited after transfection with the wild type but not mutant EPO enhancer fragment. These results indicate that HIF-1 regulates hypoxia-stimulated induction of Kv1.2 Kv1.5, Kv2.1, and Kv9.3 channels in cultured PASMCs.
authors.affiliation: Ion Channelopathy Research Center, Institute of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.forename: Ning
authors.initials: N
authors.lastname: Zhao
authors.forename: Cheng-Kun
authors.initials: CK
authors.lastname: Xia
authors.forename: Li-li
authors.initials: LL
authors.lastname: Du
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Fu
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Du
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004742:Enhancer Elements, Genetic; D004921:Erythropoietin / Q000235:genetics; D015870:Gene Expression; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051663:Kv1.2 Potassium Channel / Q000235:genetics; D051666:Kv1.5 Potassium Channel / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics; D016716:PC12 Cells; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D011651:Pulmonary Artery / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051669:Shab Potassium Channels / Q000235:genetics; D014162:Transfection
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C496991:Kcnb1 protein, rat; D051663:Kv1.2 Potassium Channel; D051666:Kv1.5 Potassium Channel; D050505:Mutant Proteins; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D004921:Erythropoietin; D004247:DNA