Effects of atorvastatin on time-dependent change of fast sodium current in simulated acute ischaemic ventricular myocytes.

Abstract

Our previous experiments showed that the transient sodium current (INa) was abnormally increased in early ischaemia and atorvastatin could inhibit INa. The aim of this study was to observe the time-dependent effects of simulated ischaemia on INa and characterise the direct effects of atorvastatin on ischaemic INa. Left ventricular myocytes were isolated from Wistar rats and randomly divided into two groups: a control group (normal to simulated ischaemia) and a statin group (normal to simulated ischaemia with 5 µmol/l atorvastatin). The INa was recorded under normal conditions (as baseline) by whole-cell patch clamp and recorded from three to 21 minutes in the next phase of simulated ischaemic conditions. In the control group, normalised INa (at -40 mV) was increased to the peak (1.15 ± 0.08 mA) at three minutes of ischaemia compared with baseline (0.95 ± 0.04 mA, p < 0.01), it subsequently returned to baseline levels at nine and 11 minutes of ischaemia (0.98 ± 0.12 and 0.92 ± 0.12 mA, respectively), and persistently decreased with prolonged ischaemic time. In the statin group, there were no differences between baseline and the early stages of ischaemia (0.97 ± 0.04 mA at baseline vs 0.92 ± 0.12 mA in ischaemia for three minutes, p > 0.05). Our results suggest that, in the early stages of ischaemia, changes in INa in ventricular myocytes are time-dependent, showing an initial increase followed by a decrease, while atorvastatin inhibited the transient increase in INa and made the change more gradual.