HUMAN & EXPERIMENTAL TOXICOLOGY, vol.32, no.1, pp.62-69, 2013 (SCI-Expanded)
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 mu M, 10 mu M and 50 mu M). In other groups, each atrium was incubated with selective adenosine A(1) antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 10(-4) M) or selective adenosine A(2a) 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 (APD(50) and APD(80), respectively), and the maximum rise and decay slopes of AP were recorded. Amitriptyline (50 mu M) prolonged the APD(50) and APD(80) (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 mu M (p < 0.01). DPCPX significantly decreased the 50-mu M amitriptyline-induced APD(50) and APD(80) prolongation (p < 0.001). DPCPX significantly prevented the effects of amitriptyline (1 mu M and 50 mu M) on maximum rise slope of AP (p < 0.05). DPCPX significantly prevented the amitriptyline-induced (50 mu M) reduction in maximum decay slope of AP (p < 0.001). The selective adenosine A(1) receptor antagonist prevented the electrophysiological effects of amitriptyline on atrial AP. A(1) receptor stimulation may be responsible for the cardiovascular toxic effects produced by amitriptyline.