Evidence for Arrhythmogenic Effects of A_2A-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.