Simulated blocking potassium channels medication on variant mutant SCN5A sodium channels

Two gene-mutant sodium channels, 1795insD and I1768V, were considered to be the possible molecular markers in the initiation of long QT (LQT) syndrome. The 1795insD, which decreases the channel availability and enhances the inactivation, and 11768V, which increases the channel availability and enhances the rate of recovery from inactivation, have the ability to induce LQT regardless of their heterogeneous physical characteristics. However, their arrhythmic susceptibility with the use of certain antiarrhythmic medications has not yet been examined closely. In this study, the two mutant SCN5A channels were explored to elucidate the interactions among various potassium channels, IK1, IKr, and IKs with simulated antiarrhythmic medications by computer modeling. The two mutant SCN5A Markov models, adapted to fit into Rudy's ventricular cell model, performed numerical calculation by using cvode, an ODE solver, with C code in a 4-node PC cluster. In this study, our previously developed S1-S2 protocol was used to investigate the cell excitability in simulated blocking potassium channel medication. The results are as follows: (1) by blocking IK1 from 10% to 80%, the needed injection charges to initiate an action potential for 1795insD were smaller than I1768V's; (2) by blocking 70% IKr with current stimuli at the rate of 0.5 Hz, the action potential of 11768V at the 4 beat began to display premature repolarization; and (3) by blocking 40% -50% IKs with current stimuli at the rates of 0.5 Hz and 1 Hz respectively, the action potential of I1768V at the 3r beat and the 7t beat began to display premature repolarization. Accordingly, the blockage of IK1 could demonstrate both positive and negative effects on the two mutant SCN5A channels, as it may enhance or reduce the channel availability while increasing or decreasing the charge threshold. In addition, the blockage of IKs for I1768V might cause serious premature repolarization than the blockage of IKr