Reduced sodium current amplitude and current-voltage kinetics in myocytes with reduced ankyrin-G expression. Nontransduced cardiomyocytes (control) and cardiomyocytes transduced with human- (hAnkG) or rat-specific (rAnkG) shRNA virus were analyzed for Na_v1.5 current. (A–C) Whole-cell patch clamp sodium current traces elicited control (A; 17 pF), human ankyrin-G–specific shRNA–transduced cells (B; 18 pF), and rat-specific ankyrin-G shRNA–transduced cells (C; 16.8 pF). All cardiomyocytes displayed similar cell capacitance, and all traces are normalized for cell capacitance. (D) Mean and normalized current-voltage relationship for neonatal rat ventricular cardiomyocytes treated with control virus (black squares; n = 10), human ankyrin-G shRNA virus (gray circles; n = 10), and rat ankyrin-G shRNA virus (white squares; n = 10). (E) Normalized maximum sodium current amplitude in myocytes treated with control (black bar) and rat- (white bar) and human (gray bar)-specific ankyrin-G shRNA virus. *, P < 0.05. (F and G) Reduced ankyrin-G expression specifically affects cardiomyocyte sodium current. (F) Amplitude of Na⁺ and Ca²⁺ current in nontransduced (control) and rat neonatal cardiomyocytes transduced with ankyrin-G species-specific shRNA viruses. Currents are elicited with the protocol shown in the inset (see Materials and methods for details). Left panels depict Na⁺ and Ca²⁺ current in cardiomyocytes treated with control or human ankyrin-G–specific shRNA virus (hAnkG shRNA). Right panels display the significant decrease in I_Na, but not I_Ca, in cardiomyocytes transduced with rat-specific ankyrin-G shRNA virus (rAnkG shRNA). All traces are normalized for cell capacitance. (G) Reduced ankyrin-G expression leads to reduced I_Na but does not affect cardiomyocyte I_Ca. (E and G) Data are plotted as mean ± SEM (error bars; n = 10). Statistical difference was analyzed by analysis of variance.