Overexpression of atrial adenosine2A receptors induced by high-rate pacing stimulation: a new step in the molecular remodeling of the atria

Abstract

Recently, an association between atrial fibrillation (AF) and a local increase in sarcoplasmic calcium release was suggested as a mechanism able to generate afterdepolarizations and promote arrhythmias recurrence. The adenosine A2A receptors (A2A) are expressed in the atria, modulate the frequency of spontaneous calcium release, and may be involved in the remodeling process during AF. Aim: To investigate the role of atrial adenosine receptors by analyzing A1 and A2A receptor protein levels through changes in their transcriptional control during atrial high-rate. Methods: The high-right atrium of anesthetized, artificially ventilated rats (n=10; age 12 weeks) was paced epicardially for 2 hours (50Hz). Animals were sacrificed and separate samples of the atria collected for A1 and A2A mRNA Real Time PCR quantification. The housekeeping gene 18SrRNA was used as internal control for the quantification of receptors mRNA. A sham group was used as control (matching number, age and sex). CT values were calculated for each sample, and converted into relative quantities with the ΔCTmethod (Eq.1: ΔCT=CTAdora-CT18SrRNA; Eq.2: ΔΔCT=ΔCTcontrols- ΔCTStimulation). The effects of high-rate pacing were evaluated by one way analysis of variance (significance if P<0.05). Results: After 2 hours of high-rate pacing, real time PCR showed a significant increase of A2A mRNA expression levels (ΔCTA2A 16,8±2.72 vs. 11,2±2.64; p<0.001), and a steady maintenance of the A1 mRNA levels. No differences between right and left atrium were observed. ![Figure][1] Figure 1. Adenosine receptors remodeling Conclusions: Sustained atrial high-rate stimulation induces an early overexpression of A2A receptors, suggesting an impairment of the cross-talk between atrial A1 and A2A receptors. This can be associated with a role for A2A receptors in atrial Ca2+ kinetics and atrial remodeling. [1]: pending:yes