[Effect of simulated ischemia on activity and heterogeneity of Na+ channel in rabbit ventricular epicardial, midmyocardial and endocardial myocytes].

ABSTRACT

OBJECTIVE: To study the ionic mechanism of reentrant arrhythmia. METHODS: Single myocytes were enzymatically isolated from the epicardium, midmyocardium and endocardium of the left ventricle free wall of rabbit, followed by whole-cell patch-clamp recording of the Na(+) current (I(Na)) of the 3 cellular subtypes (superfused with normal and then simulated ischemia solution). The currents in the 3 cellular subtypes before and after simulated ischemia lasting for 10, 20, and 30 min, respectively, were compared. RESULTS: No changes was recorded in the configuration of the I-V curves and voltage dependence of I(Na) after simulated ischemia, and the peak I(Na) densities (- 20 mV) were significantly reduced in the 3 cellular subtypes compared with those recorded in normal condition. At the same time, the differences in I(Na) peak current densities in the 3 cellular subtypes underwent variations after simulated ischemia. Simulated ischemia resulted in obvious shift of I(Na) steady-state inactivation curves in the hyperpolarizing direction in the 3 cellular subtypes and inactivation was accelerated, and the differences in the half maximal inactivation voltages (V0.5) between the 3 cellular subtypes were also altered after simulated ischemia. After simulated ischemia, I(Na) recovery from inactivation in the epicardium, endocardium and midmyocardium was all slowed down in comparison with that in normal condition, but without statistical significance. Differences between the recovery curves of three cellular subtypes were noted after ischemia for 30 min. CONCLUSION: Ischemia can affect the activity of Na(+) channel, disrupting the balance of ion channel currents and the heterogeneity of I(Na) among the 3 cellular subtypes, which is responsible for the onset of arrhythmia and partially explains different pharmacological reactions of the 3 cellular subtypes under normal and ischemic conditions.