Effects of Simvastatin on Ion Channel Currents in Ventricular Myocytes from Acute Infarcted Heart of Normocholesterolemic Rabbits

Chao Ding; Xianghua Fu; Li Yang; Huixiao Chen; Junxia Li; Yuying Zhao; Jie Li; Jie Wang

摘要：Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rab-bit heart suffering from acute myocardial infarction (AMI), so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Methods Forty-five New Zealand rabbits were randomly divided into three groups: AMI group, simv-astatin 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. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region 72 h later. Whole cell patch clamp technique was used to record membrane ionic currents, inclu-ding sodium current (Ina), L-type calcium current (Ica-L) and transient outward potassium current (Ito). Results ① There was not significant difference in serum cholesterol concentration among three groups. ② The peak Ina current den-sity (at -30 mV) was significantly decreased in AMI group (-25.26±5. 28, n = 13), comparing with CON (-42. 78±5.48, n = 16), P < 0. 05, while it was significantly increased in Statin group (-39. 83±5. 65 pA/pF, n = 12) comparing with AMI group, P <0. 01; The peak I Ca-L current density (at 0 mV) was significantly decreased in AMI group (- 3.43±0. 92 pA/pF, n = 13) comparing with CON (- 4. 56±1.01 pA/pF, n = 15), P < 0. 05, while it was significantly increased in Statin group (-4. 18±0. 96 pA/pF, n = 12) comparing with AMI group, P <0. 05; The Ito current density (at + 60 mV) was significantly decreased in AMI group (11.41±1.94 pA/pF, n = 13) compa-ring with CON (17. 41±3. 13 pA/pF, n = 15), P <0. 01, while it was significantly increased in Statin group (16. 11±2. 43 pA/pF, n = 14) comparing with AMI group, P < 0. 01. Conclusions AMI induces significant down-regula-tion of Ina, I Ca-L and Ito. Pretreatment with simvastatin could attenuate this change without lowering the serum cholester-ol level, suggesting that simvastatin could reverse this electrical remodeling, thus contributing to the ionic mechanism of statin treatment for antiarrhythmia.