Abnormal Calcium Handling in Atrial Fibrillation Is Linked to Up-Regulation of Adenosine A2A Receptors

Study Questions:

Is atrial fibrillation (AF) associated with increased expression of adenosine receptors?


Right atrial biopsies were performed at the time of open-heart surgery in 51 patients (mean age 64 years) with no history of AF, and in 31 patients (mean age 70 years) with AF. Biochemical and electrophysiological testing were performed on isolated atrial myocytes.


There was greater expression of the A2A receptor in patients with AF than in patients without AF. Stimulation of A2A receptors in patients with AF significantly increased phosphorylation of ryanodine receptors, and was associated with a major increase in spontaneous release of calcium from the sarcoplasmic reticulum (SR). Calcium release from the SR was augmented by intracellular perfusion with adenosine and was attenuated by A2A receptor antagonists and by removal of adenosine from the cytosol.


Patients with AF have up-regulation of the adenosine A2A receptor, resulting in a greater degree of spontaneous calcium release from the SR in atrial myocytes.


Adenosine-triggered intracellular calcium release probably explains why the administration of adenosine in patients with paroxysmal supraventricular tachycardia sometimes induces AF. The higher intracellular calcium levels can promote arrhythmogenesis through afterdepolarizations that cause triggered activity. The results of this study indicate that endogenous adenosine and up-regulation of adenosine receptors may be important in the genesis of spontaneous AF. An important clinical implication is that A2A receptor antagonists might be effective rhythm-control agents in patients with AF.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Genetic Arrhythmic Conditions, Lipid Metabolism

Keywords: Receptors, Purinergic P1, Ryanodine Receptor Calcium Release Channel, Heart Atria, Heart, Sarcoplasmic Reticulum, Receptor, Adenosine A2A, Phosphorylation, Up-Regulation, Calcium

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