Inhibition by agmatine on spontaneous activity of rabbit atrioventricular node cells

AIM: To study the effects of agmatine on spontaneous activity of atrioventr icular (AV) node and its action mechanisms. METHODS: Action potentials in A V node cells were recorded using intracellular microelectrode technique. RE SULTS: Agmatine not only reduced the amplitude of action potential (APA), m aximal rate of depolarization (V-max), velocity of diastolic (phase 4) depo larization (VDD), and rate of spontaneous firing (RSF), but also prolonged 90 % duration of action potential (APD(90)) in a concentration-dependent ma nner. The effects of agmatine (10 mmol/L) could be blocked completely by pr etreatment with idazoxan (0.1 mmol/L), an imidazoline receptor (IR) and alp ha(2)-adrenergic receptor(alpha(2)-AR) antagonist. Pretreatment with N-G-ni tro-L-arginine methyl ester (L-NAME, 0.5 mmol/L), a nitric oxide (NO) synth ase inhibitor, did not affect the effects of agmatine on AV node cells. Ele vation of Ca2+ concentration (5 mmol/L) in perfusate antagonized the effect s of agmatine (10 mmol/L). Lemakalim (30 mu mol/L), an ATP-sensitive potass ium channel opener, inhibited the prolonging effects of agmatine on repolar ization. CONCLUSION: The inhibitory effects of agmatine on spontaneous acti vity of AV node cells in rabbits were likely mediated by IR and/or alpha(2) -AR, and were related to the reduction in calcium influx and potassium effl ux.