RT Journal Article
T1 Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of Kir2.1 channels
A1 Gómez García, Ricardo
A1 Caballero Collado, Ricardo
A1 Barana Muñoz, Adriana
A1 Amorós García, Irene
A1 Calvo, Enrique
A1 López, Juan Antonio
A1 Klein, Helene
A1 Vaquero González, Luis Miguel
A1 Osuna, Lourdes
A1 Atienza Fernández, Felipe
A1 Almendral Garrote, Jesús
A1 Pinto, Ángel
A1 Tamargo Menéndez, Juan
A1 Delpón Mosquera, María Eva
AB 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.
PB American Heart Association
SN 0009-7330
YR 2009
FD 2009-08-14
LK https://hdl.handle.net/20.500.14352/92164
UL https://hdl.handle.net/20.500.14352/92164
LA eng
NO 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
NO Ministerio de Educación y Ciencia
NO Ministerio de Sanidad y Consumo
NO Comunidad de Madrid
NO Instituto de Salud Carlos III
NO Fundación LILLY
NO Centro Nacional de Investigaciones Cardiovasculares
DS Docta Complutense
RD 10 abr 2025