Chronic atrial fibrillation up-regulates β1-Adrenoceptors affecting repolarizing currents and action potential duration.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Department of Pharmacology,  School of Medicine, Universidad Complutense de Madrid, Madrid 28040,  Spain.
Marta
M
González de la Fuente
Adriana
A
Barana
Ricardo
R
Gómez
Irene
I
Amorós
Pablo
P
Dolz-Gaitón
Sandra
S
Sacristán
Felipe
F
Atienza
Ana
A
Pita
Ángel
Á
Pinto
Francisco
F
Fernández-Avilés
Ricardo
R
Caballero
Juan
J
Tamargo
Eva
E
Delpón
D000200:Action Potentials / Q000187:drug effects; D000368:Aged; D001281:Atrial Fibrillation / Q000503:physiopathology*; D002908:Chronic Disease; D005260:Female; D006325:Heart Atria / Q000503:physiopathology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D013997:Time Factors
D018342:Receptors, Adrenergic, beta-1; D007545:Isoproterenol