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[PMID]: | 28743763 |
[Au] Autor: | Al-Owais MM; Hettiarachchi NT; Kirton HM; Hardy ME; Boyle JP; Scragg JL; Steele DS; Peers C |
[Ad] Endereço: | Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom; and. |
[Ti] Título: | A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K channels in carbon monoxide-induced proarrhythmic early afterdepolarizations. |
[So] Source: | FASEB J;31(11):4845-4854, 2017 11. | [Is] ISSN: | 1530-6860 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Exposure to CO causes early afterdepolarization arrhythmias. Previous studies in rats have indicated that arrhythmias arose as a result of augmentation of the late Na current. The purpose of the present study was to examine the basis for CO-induced arrhythmias in guinea pig myocytes in which action potentials (APs) more closely resemble those of human myocytes. Whole-cell current- and voltage-clamp recordings were made from isolated guinea pig myocytes as well as from human embryonic kidney 293 (HEK293) cells that express wild-type or a C723S mutant form of ether-a-go-go-related gene (ERG; Kv11.1). We also monitored the formation of peroxynitrite (ONOO ) in HEK293 cells fluorimetrically. CO-applied as the CO-releasing molecule, CORM-2-prolonged the APs and induced early afterdepolarizations in guinea pig myocytes. In HEK293 cells, CO inhibited wild-type, but not C723S mutant, Kv11.1 K currents. Inhibition was prevented by an antioxidant, mitochondrial inhibitors, or inhibition of NO formation. CO also raised ONOO levels, an effect that was reversed by the ONOO scavenger, FeTPPS [5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrinato-iron(III)], which also prevented the CO inhibition of Kv11.1 currents and abolished the effects of CO on Kv11.1 tail currents and APs in guinea pig myocytes. Our data suggest that CO induces arrhythmias in guinea pig cardiac myocytes the ONOO -mediated inhibition of Kv11.1 K channels.-Al-Owais, M. M., Hettiarachchi, N. T., Kirton, H. M., Hardy, M. E., Boyle, J. P., Scragg, J. L., Steele, D. S., Peers, C. A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K channels in carbon monoxide-induced proarrhythmic early afterdepolarizations. |
[Mh] Termos MeSH primário: |
Arritmias Cardíacas/metabolismo Monóxido de Carbono/toxicidade Canal de Potássio ERG1/metabolismo Potenciais da Membrana/efeitos dos fármacos Miócitos Cardíacos/metabolismo Ácido Peroxinitroso/metabolismo
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[Mh] Termos MeSH secundário: |
Animais Arritmias Cardíacas/induzido quimicamente Arritmias Cardíacas/genética Arritmias Cardíacas/patologia Canal de Potássio ERG1/genética Cobaias Células HEK293 Seres Humanos Metaloporfirinas/farmacologia Miócitos Cardíacos/patologia Óxido Nítrico/genética Óxido Nítrico/metabolismo Compostos Organometálicos/farmacologia Ácido Peroxinitroso/genética
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride); 0 (ERG1 Potassium Channel); 0 (KCNH2 protein, human); 0 (Metalloporphyrins); 0 (Organometallic Compounds); 0 (tricarbonyldichlororuthenium (II) dimer); 14691-52-2 (Peroxynitrous Acid); 31C4KY9ESH (Nitric Oxide); 7U1EE4V452 (Carbon Monoxide) |
[Em] Mês de entrada: | 1711 |
[Cu] Atualização por classe: | 180306 |
[Lr] Data última revisão:
| 180306 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170727 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1096/fj.201700259R |
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