Abstract: AIM:To investigate the effect of stimulating β3adrenergic receptors (β3ARs) on Ltype calcium current (ICa,L) in atrial myocytes of rapid atrial pacing (RAP) rabbits. METHODS: Thirty seven rabbits (20-25 kg) were randomly divided: for ex vivo study in shamoperated group (sham group, n=7), thoracotomy was performed and pacemakers were implanted but not paced. Atrial myocytes were isolated after 1 week and ICa,L was recorded (sham group). In the operation group (n=7), rabbits were paced at 600 beats per minute for 1 week, atrial myocytes were isolated and ICa,L was recorded (RAP group). Atrial myocytes were then treated with β1, β2ARs blocker nadolol and β3ARs agonist BRL 37344 (BRL) and ICa,L was recorded (RAP+BRL group). Finally, atrial myocytes were incubated by β3ARs selective antagonist SR 59230A (SR) and ICa,L was recorded (RAP+BRL+SR group). For in vivo study: RAP group (n=7) with RAP for 1 week, RAP+BRL group (n=7) with RAP plus nadolol and BRL for 1 week, and RAP+BRL+SR group (n=7) with RAP plus nadolol, BRL and SR for 1 week. Nitric oxide (NO), cyclic guanosine monophosphate (cGMP) and the protein expressions of cGMPdependent protein kinases (PKG) were measured in each group. RESULTS: Compared with that in sham group, the density of ICa,L obviously decreased in the RAP group (P<0001) and compared with those in RAP group, the density of ICa,L obviously decreased (P<001) and the NO production, cGMP content and PKG protein expression obviously increased in RAP+BRL group (P<005). Compared with those in the RAP+BRL group, the density of ICa,L obviously increased (P<001) and NO production, cGMP content and PKG protein expression obviously decreased in RAP+BRL+SR group (P<0001, P<001, P<005). CONCLUSION: Activation of β3ARs decreases ICa,L in RAP rabbit atrial myocytes accompanied by stimulation of NOcGMPPKG signal pathway.