The role of adenosine receptors on amitriptyline-induced electrophysiological changes on rat atrium

Abstract

We investigated the role of adenosine receptors in amitriptyline-induced cardiac action potential (AP) changes in isolated rat atria. In the first group, APs were recorded after cumulative addition of amitriptyline (1 μM, 10 μM and 50 μM). In other groups, each atrium was incubated with selective adenosine A1 antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 10−4 M) or selective adenosine A2a receptor antagonist (8-(3-chlorostyryl) caffeine, 10−5 M) before amitriptyline administration. Resting membrane potential, AP amplitude (APA), AP duration at 50% and 80% of repolarization (APD50 and APD80, respectively), and the maximum rise and decay slopes of AP were recorded. Amitriptyline (50 μM) prolonged the APD50 and APD80 ( p < 0.001) and the maximum rise slope of AP was reduced by amitriptyline ( p < 0.0001). Amitriptyline reduced maximum decay slope of AP only at 50 μM ( p < 0.01). DPCPX significantly decreased the 50-μM amitriptyline-induced APD50 and APD80 prolongation ( p < 0.001). DPCPX significantly prevented the effects of amitriptyline (1 μM and 50 μM) on maximum rise slope of AP ( p < 0.05). DPCPX significantly prevented the amitriptyline-induced (50 μM) reduction in maximum decay slope of AP ( p < 0.001). The selective adenosine A1 receptor antagonist prevented the electrophysiological effects of amitriptyline on atrial AP. A1 receptor stimulation may be responsible for the cardiovascular toxic effects produced by amitriptyline.