Evidence for Arrhythmogenic Effects of A2A-Adenosine Receptors

Adenosine can be released from the heart and may stimulate four different cardiac adenosine receptors. A receptor subtype that couples to the generation of cyclic adenosine monophosphate (cAMP) is the A 2A -adenosine receptor (A 2A -AR). To better understand its role in cardiac function, we studied mechanical and electrophysiological effects in transgenic mice that overexpress the human A 2A -AR in cardiomyocytes (A 2A -TG). We used isolated preparations from the left atrium, the right atrium, isolated perfused hearts with surface electrocardiogram (ECG) recording, and surface body ECG recordings of living mice. The hypothesized arrhythmogenic effects of transgenicity per se and A 2A -AR stimulation were studied. We noted an increase in the incidence of supraventricular and ventricular arrhythmias under these conditions in A 2A -TG. Moreover, we noted that the A 2A -AR agonist CGS 21680 exerted positive inotropic effect in isolated human electrically driven (1 Hz) right atrial trabeculae carneae. We conclude that A 2A -ARs are functional not only in A 2A -TG but also in isolated human atrial preparations. A 2A -ARs in A 2A -TG per se and their stimulation can lead to cardiac arrhythmias not only in isolated cardiac preparations from A 2A -TG but also in living A 2A -TG.