2026-06-28T04:45:22Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/921642024-02-15T01:24:57Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Gómez García, Ricardo author Caballero Collado, Ricardo author Barana Muñoz, Adriana author Amorós García, Irene author Calvo, Enrique author López, Juan Antonio author Klein, Helene author Vaquero González, Luis Miguel author Osuna, Lourdes author Atienza Fernández, Felipe author Almendral Garrote, Jesús author Pinto, Ángel author Tamargo Menéndez, Juan author Delpón Mosquera, María Eva 2024-01-10T09:10:40Z 2024-01-10T09:10:40Z 2009-08-14 Gómez R, Caballero R, Barana A, Amorós I, Calvo E, López JA, Klein H, Vaquero M, Osuna L, Atienza F, Almendral J, Pinto A, Tamargo J, Delpón E. Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of Kir2.1 channels. Circ Res. 2009 Aug 14;105(4):383-92. doi: 10.1161/CIRCRESAHA.109.197558 0009-7330 10.1161/CIRCRESAHA.109.197558 https://hdl.handle.net/20.500.14352/92164 https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.109.197558 https://pubmed.ncbi.nlm.nih.gov/19608980/ Rationale: The cardiac inwardly rectifying K(+) current (I(K1)) plays a critical role in modulating excitability by setting the resting membrane potential and shaping phase 3 of the cardiac action potential. Objective: This study aims to analyze the effects of nitric oxide (NO) on human atrial I(K1) and on Kir2.1 channels, the major isoform of inwardly rectifying channels present in the human heart. Methods and results: Currents were recorded in enzymatically isolated myocytes and in transiently transfected CHO cells, respectively. NO at myocardial physiological concentrations (25 to 500 nmol/L) increased inward and outward I(K1) and I(Kir2.1). These effects were accompanied by hyperpolarization of the resting membrane potential and a shortening of the duration of phase 3 of the human atrial action potential. The I(Kir2.1) increase was attributable to an increase in the open probability of the channel. Site-directed mutagenesis analysis demonstrated that NO effects were mediated by the selective S-nitrosylation of Kir2.1 Cys76 residue. Single ion monitoring experiments performed by liquid chromatography/tandem mass spectrometry suggested that the primary sequence that surrounds Cys76 determines its selective S-nitrosylation. Chronic atrial fibrillation, which produces a decrease in NO bioavailability, decreased the S-nitrosylation of Kir2.1 channels in human atrial samples as demonstrated by a biotin-switch assay, followed by Western blot. Conclusions: The results demonstrated that, under physiological conditions, NO regulates human cardiac I(K1) through a redox-related process. eng Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of Kir2.1 channels journal article 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URL https://docta.ucm.es/bitstreams/ba17e368-fc94-45c3-ad60-31263112312e/download File MD5 bbf4e503fc04f9a6d5b1b29b3443efce 681938 application/pdf 15-FA_Gómez_Circ-Res_2009.pdf