RT Journal Article
T1 Chronic atrial fibrillation up-regulates β1-Adrenoceptors affecting repolarizing currents and action potential duration
A1 González de la Fuente, Marta
A1 Barana Muñoz, Adriana
A1 Gómez García, Ricardo
A1 Amorós García, Irene
A1 Dolz Gaitón, Pablo
A1 Sacristán, Sandra
A1 Atienza Fernández, Felipe
A1 Pita Fernández, Ana
A1 Pinto, Ángel
A1 Fernández-Avilés Díaz, Francisco Jesús
A1 Caballero Collado, Ricardo
A1 Tamargo Menéndez, Juan
A1 Delpón Mosquera, María Eva
AB Aims: β-adrenergic stimulation has profound influence in the genesis and maintenance of atrial fibrillation (AF). However, the effects of β-Adrenoceptor stimulation on repolarizing currents and action potential (AP) characteristics in human atrial myocytes from left (LAA) and right atrial appendages (RAA) obtained from sinus rhythm (SR) and chronic atrial fibrillation (CAF) patients have not been compared yet.Methods and results: Currents and APs were recorded using whole-cell patch-clamp in RAA and LAA myocytes from SR and CAF patients. Isoproterenol concentration-dependently decreased the Ca(2+)-independent 4-aminopyridine-sensitive component of the transient outward current (I(to1)) and the inward rectifying current (I(K1)). CAF significantly enhanced this inhibition, this effect being more marked in the left than in the right atria. CAF dramatically enhanced β-Adrenoceptor-mediated increase in the slow component of the delayed rectifier current (I(Ks)), whose density was already markedly increased by CAF. Conversely, the ultrarapid component of the delayed rectifier current (I(Kur)) of both SR and CAF myocytes was insensitive to low isoproterenol concentrations. As a consequence, stimulation of β1-Adrenoceptors in SR myocytes lengthened, whereas in CAF myocytes shortened, the AP duration. Quantitative PCR revealed that CAF up-regulated β1-Adrenoceptor expression, preferentially in the left atria.Conclusion: The present results demonstrate that CAF increases the effects of β1-Adrenoceptor stimulation on repolarizing currents by means of a chamber-specific up-regulation of the receptors. This, together with the ion channel derangements produced by CAF, could contribute to the long-term stabilization of the arrhythmia by shortening the AP duration.
PB Oxford University Press
SN 0008-6363
YR 2013
FD 2013-02-01
LK https://hdl.handle.net/20.500.14352/93572
UL https://hdl.handle.net/20.500.14352/93572
LA eng
NO González de la Fuente M, Barana A, Gómez R, Amorós I, Dolz-Gaitón P, Sacristán S, Atienza F, Pita A, Pinto Á, Fernández-Avilés F, Caballero R, Tamargo J, Delpón E. Chronic atrial fibrillation up-regulates β1-Adrenoceptors affecting repolarizing currents and action potential duration. Cardiovasc Res. 2013 Feb 1;97(2):379-88. doi: 10.1093/cvr/cvs313
NO Ministerio de Ciencia e Innovación
NO Centro Nacional de Investigaciones Cardiovasculares
NO Instituto de Salud Carlos III
NO Comunidad de Madrid
NO Sociedad Española de Cardiología
DS Docta Complutense
RD 8 abr 2025