Effects of Atorvastatin on Transient Sodium Currents in Rat Normal, Simulated Ischemia, and Reperfusion Ventricular Myocytes

Abstract

Objectives: (1) To detect the whether the effects of simulated ischemia on I_Na of rat left ventricular myocytes in a time-dependent manner and the effects of atorvastatin on ischemia I_Na; (2) To investigate the effects of atorvastatin on I_Na of rat-simulated ischemia/reperfusion (I/R) ventricular cells. Materials and Methods: Ventricular cells were enzymatically isolated by Langendorff perfusion system. Whole-cell patch clamp was applied to detect I_Na level. Some elements of extracellular fluid were hanged to simulate the status of normal, I and R condition. Then the effects of atorvastatin on I_Na were observed. Results: (1) During simulated reperfusion, I_Na decreased and atorvastatin further suppressed the reduction degree. (2) At test potential –40 mV, no difference was detected among peak I_Na amplitude of ischemia for 20 min, reperfusion phase 3/5/7/9 min in continuous ischemia (I) group (p = 0.275). In I/R group, peak I_Na amplitude continuously decreased at 3 min (p = 0.005) and 9 min (p = 0.041). In atorvastatin intervention + I/R (Statin + I/R) group, peak I_Na amplitude at reperfusion 3 min decreased compared with ischemia phase (p = 0.000), while no significant difference was detected between 3 and 9 min (p = 0.858). The differences were significant at the same time point between groups. At reperfusion 3/5/7/9 min, peak I_Na of the I/R group was lower than the ischemia group (all p = 0.000), same as the Statin + I/R group (p = 0.000, p = 0.003, p = 0.006, and p = 0.001). Peak I_Na of the Statin + I/R group was higher than the I/R group at the same time point (p = 0.011, p = 0.033, p = 0.003, p = 0.003). There was no change in the I group during reperfusion phase (p > 0.05). In I/R group, V_1/2 (mV) shifted from –58.87 ± 3.36 to –54.33 ± 2.40, k (mV) shifted from 1.25 ± 0.59 to 1.91 ± 0.84 (p < 0.05). In the Statin + I/R group, V_1/2 (mV) increased from –57.80 ± 2.97 to –52.76 ± 3.14 (p < 0.01), no change was observed in k (p > 0.05). Conclusions: (1) In the status of reperfusion, I_Na decreased more than that in the status of ischemia. (2) Atorvastatin protected the cells from reduction of I_Na during long-time simulated (>15 min) I/R. (3) Overall, atorvastatin affected I_Na of the normal, simulated ischemic/reperfusion cell in rat left ventricle by blocking sodium channel ­directly.