Effects of simvastatin on Ion Channel Currents in ventricular myocytes from rabbit with acute myocardial infarction

Objective To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rabbit heart suffering from acute myocardial infarction(AMI),so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Methods Fourty-five New Zeland rabbits were randomly divided into three groups: AMI group, simvastatin intervention group (Statin group) and sham-operated control group (CON). Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg?kg-1?d-1 (Statin group) or placebo (AMI group) for 3 days. 24 h later, single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region .Whole cell patch clamp technique was used to record membrane ionic currents, including sodium current (INa), L-type calcium current (ICa-L) and transient outward potassium current (Ito). Results There was not significant difference in serum cholesterol concentration among three groups. The peak INa current density(at –30 mV) was significantly decreased in AMI group (–23.26±5.18,n=12),) ompared with CON (–42.78±5.48 , n=16), P<0.05,while it was significantly increased in Statin group (–39.23±5.45 pA/pF, n=13) compared with AMI group, P<0.01;The peak ICa-L current density (at 0 mV) was significantly decreased in AMI group (–3.23±0.91 pA/pF, n=12) compared with CON (–4.56±1.01 pA/pF,n= 15),P<0.05,while it was significantly increased in Statin group (–4.18±0.95 pA/pF, n= 12) compared with AMI group, P<0.05; The Ito current density(at +60 mV) was significantly decreased in AMI group (10.41 ±1.93 pA/pF, n=12) compared with CON (17.41± 3.13 pA/pF , n=15), P<0.01, while it was significantly increased in Statin group (16.21 ± 2.42 pA/pF , n=13) compared with AMI group, P<0.01. Conclusions AMI induces significant down-regulation of INa, ICa-L and Ito pretreatment with simvastatin could attenuate this change without lowering the serum cholesterol level, suggesting that simvastatin could reverse this electrical remodeling, thus contributing to the ionic mechanism of statin treatment for antiarrhythmia .