Figure 4.

Estimation and illustration of the effects of ranolazine on CO-induced changes in the action potential and underlying I_Na-L, I_Ca-L, and Na⁺/Ca²⁺ exchange currents (I_NCX) in human ventricle. The effects of ranolazine (shown in black) were modeled as a selective 50% reduction in the I_Na-L. Note that this reduces action potential, duration of every 3rd action potential, as well as decreasing the incidence and the frequency of EADs. However, these changes are complex. APD (Panel A) as well as [Ca²⁺]_i and I_NCX records all show variations or alternans, even at this fixed stimulus rate (1 Hz). Panel (C) illustrates the corresponding ranolazine-induced changes in the I_NCX. Note that in the action potential traces showing a ranolazine-induced shortening of APD, there is no spontaneous inward I_NCX current (see also Figure 5 and Results). The arrows denote the “extra” EADs (Panel A), and underlying [Ca²⁺]_i transient (Panel B), and I_NCX (Panel C) records.