Hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle cells. 2009

Amy L Firth, and Oleksandr Platoshyn, and Elena E Brevnova, and Elyssa D Burg, and Frank Powell, and Gabriel H Haddad, and Jason X-J Yuan
Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0725, USA.

Acute hypoxia induces pulmonary vasoconstriction and chronic hypoxia causes pulmonary vascular remodeling characterized by significant vascular medial hypertrophy. Electromechanical and pharmacomechanical mechanisms are involved in regulating pulmonary vasomotor tone, while changes in cytosolic Ca2+ concentration ([Ca2+](cyt)) are an important signal in regulating contraction and proliferation of pulmonary artery smooth muscle cells (PASMC). Hypoxia-induced increases in [Ca2+](cyt) are, in part, mediated by selective inhibition of voltage-gated K+ (Kv) channels in PASMC. Kv1.5, encoded by the KCNA5 gene, is a Kv channel alpha subunit that forms functional homotetrameric and heterotetrameric Kv channels in PASMC. Activity of Kv channels contributes to the regulation of resting membrane potential. Overexpression of the human KCNA5 gene in rat PASMC and other cell types increases whole-cell Kv currents and causes membrane hyperpolarization. However, acute hypoxia only reduced Kv currents in KCNA5-transfected PASMC. These results provide compelling evidence that Kv1.5 is an important hypoxia-sensitive Kv channel in PASMC, contributing to regulation of membrane potential and intracellular Ca2+ homeostasis during hypoxia. This hypoxia-sensitive mechanism essential for inhibiting Kv1.5 channel activity is exclusively present in PASMC.

UI MeSH Term Description Entries
D011651 Pulmonary Artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Arteries, Pulmonary,Artery, Pulmonary,Pulmonary Arteries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002522 Chlorocebus aethiops A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research. African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000860 Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms. Anoxia,Oxygen Deficiency,Anoxemia,Deficiency, Oxygen,Hypoxemia,Deficiencies, Oxygen,Oxygen Deficiencies
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D051666 Kv1.5 Potassium Channel A delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA. KCNA5 Potassium Channel,Potassium Channel, KCNA5,Potassium Channel, Kv1.5
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out

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