RT Journal Article
T1 Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism
A1 Núñez Fernández, Lucía
A1 Vaquero González, Luis Miguel
A1 Gómez García, Ricardo
A1 Caballero Collado, Ricardo
A1 Mateos Cáceres, Petra
A1 Macaya Miguel, Carlos
A1 Iriepa Canalda, Isabel
A1 Gálvez Ruano, Enrique
A1 López Farre, Antonio José
A1 Tamargo Menéndez, Juan
A1 Delpón Mosquera, María Eva
AB AbstractObjective: This study was undertaken to analyze whether nitric oxide (NO) modulates the human potassium channel hKv1.5, which generates the ultrarapid delayed rectifier current (IKur) that determines the height and duration of atrial action potentials.Methods: Currents were recorded using the whole-cell patch-clamp in Ltk- cells expressing hKv1.5 channels.Results: The NO donors (+/-)-S-Nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside, a NO solution, and l-Arginine inhibited hKv1.5 currents in a concentration-dependent manner. The NO concentration in the cell chamber was monitored using a sensor, and the IC50 for NO-induced hKv1.5 block was 340+/-70 nM. SNAP also inhibited the IKur recorded in mouse ventricular myocytes. The NO effects were partially mediated by the activation of the soluble guanylate cyclase (sGC)/cGMP/cGMP-dependent protein kinase (PKG) pathway. The biotin-switch assay demonstrated the presence of S-nitrosylated cysteines (Cys) on the hKv1.5 protein in SNAP-treated cells. Molecular modeling of hKv1.5 channel structure suggests that S-nitrosylation of Cys331 (segment 2, S2) and Cys346 (S2) would be stabilized by hydrogen bridge bonds with Ile262 (S1) and Arg342 (S2), respectively.Conclusions: NO inhibits the hKv1.5 current by a cGMP-dependent mechanism and by the S-nitrosylation of the hKv1.5 protein, an effect that contributes to shaping the human atrial action potentials.
PB Oxford University Press
SN 1755-3245
YR 2006
FD 2006
LK https://hdl.handle.net/20.500.14352/91776
UL https://hdl.handle.net/20.500.14352/91776
LA eng
NO Núñez L, Vaquero M, Gómez R, Caballero R, Mateos-Cáceres P, Macaya C, Iriepa I, Gálvez E, López-Farré A, Tamargo J, Delpón E. Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism. Cardiovasc Res. 2006 Oct 1;72(1):80-9. doi: 10.1016/j.cardiores.2006.06.021. Epub 2006 Jun 27. PMID: 16876149.
NO Fundación Mutua Madrileña 
NO Red HERACLES
DS Docta Complutense
RD 7 abr 2025