Effects of Atorvastatin on Transient Sodium Currents in Rat Normal, Simulated Ischemia, and Reperfusion Ventricular Myocytes.
(1) To detect the whether the effects of simulated ischemia on INa of rat left ventricular myocytes in a time-dependent manner and the effects of atorvastatin on ischemia INa; (2) To investigate the effects of atorvastatin on INa of rat-simulated ischemia/reperfusion (I/R) ventricular cells. Ventricular cells were enzymatically isolated by Langendorff perfusion system. Whole-cell patch clamp was applied to detect INa level. Some elements of extracellular fluid were hanged to simulate the status of normal, I and R condition. Then the effects of atorvastatin on INa were observed. (1) During simulated reperfusion, INa decreased and atorvastatin further suppressed the reduction degree. (2) At test potential -40 mV, no difference was detected among peak INa 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 INa 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 INa 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 INa 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 INa 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, V1/2 (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, V1/2 (mV) increased from -57.80 ± 2.97 to -52.76 ± 3.14 (p < 0.01), no change was observed in k (p > 0.05). (1) In the status of reperfusion, INa decreased more than that in the status of ischemia. (2) Atorvastatin protected the cells from reduction of INa during long-time simulated (>15 min) I/R. (3) Overall, atorvastatin affected INa of the normal, simulated ischemic/reperfusion cell in rat left ventricle by blocking sodium channel -directly.