AMP-activated protein kinase-alpha 2 is the main catalytic subunit of the heart, which is mainly located in cardiac myocytes. The effect of AMP-activated protein kinase-alpha 2 on the cardiac electrophysiology is barely studied. From the previous study, it is possible that AMP-activated protein kinase-alpha 2 may have some effect on the electrophysiology of the heart. To prove the hypothesis, we used the AMP-activated protein kinase-alpha 2 knockout (AMPK alpha 2(-/-) mice to estimate the electrophysiological characteristics of AMPK alpha 2(-/-) mice and try to find the mechanism between them. We used AMP-activated protein kinase-alpha 2 gene knockout (AMPK alpha 2(-/-)) mice and control wild-type mice as the experimental animals. In the experiment, we measured the monophasic action potential duration and test the inducibility to ventricular arrhythmia in isolated mice heart with and without beta-adrenoceptor antagonist metoprolol. Meanwhile, plasma concentration of catecholamine was collected. We found that AMPK alpha 2(-/-) significantly shortened 90% repolarization of monophasic action potential (MAP) (MAPD(90)) than wild-type (47.4 +/- 2.6 ms vs. 55.5 +/- 2.4 ms, n = 10, P< 0.05) and were more vulnerable to be induced to ventricular arrhythmias (70% (7/10) vs. 10% (1/10), P< 0.05), accompanied by the higher concentration of catecholamine (epinephrine: 1.75 +/- 0.18 nmol/L vs. 0.68-0.10 nmol/L n = 10, P< 0.05; norepinephrine: 9.56 +/- 0.71 nmol/L vs. 2.52 +/- 0.31 nmol/L n = 10, P< 0.05). The shortening of MAPD(90) and increased inducibility to ventricular arrhythmias of AMPK alpha 2(-/-) could almost be abolished when perfusion with beta-adrenoceptor antagonist metoprolol. It indicated that the beta-adrenoceptor activation resulting from catecholamine release was mainly responsible for the relating changes of electrophysiology of AMPK alpha 2(-/-). It had great clinical significance, as in patients who had problem with AMP-activated protein kinase-alpha 2 gene, we might use beta-adrenoceptor antagonists as the prevention of arrhythmias in future.