Interestingly, similar effects can be induced by activation of adenosine receptors (ARs) [4,5] and we have recently documented that AF is associated with elevated adenosine plasma levels (APLs) [6], which, combined with increased expression and activation of adenosine A2A receptors (A2ARs) in AF [6,7], may induce hyperphosphorylation of the cardiac ryanodine receptor (RyR2), spontaneous calcium release, afterdepolarizations, and irregular beating after elevation of the stimulation frequency observed in the atrial myocytes of patients with AF [7,8]. This evidence concerns the gene ADORA2A and atrial fibrillation.