| Summary: | 碩士 === 中華大學 === 資訊工程學系碩士班 === 93 === 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 reduces the rate of recovery from inactivation, and I1768V, 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 type3 antiarrhythmic medications have 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 RudyII ventricular cell model, were solved numerically using CVode, an ODE solver. Using our previously developed S1-S2 protocol to investigate the cell excitability in simulated blocking of potassium channel medication, the result showed (1) by blocking IK1 from 10% to 80%, the needed injection charges to initiate an action potential decreased as the blocking percentage increased, and the required charges for 1795insD were smaller than I1768V’s; (2) by blocking 90% IKr with current stimuli at the interval 1000ms, the action potential of I1768V began to display premature repolarization at the 5th beat; by blocking 80% IKr with current stimuli at the interval 1500ms, the action potential of I1768V began to display premature repolarization at the 3th beat ; and (3) by blocking 60% IKs with current stimuli at the interval 500ms ; the action potential of I1768V began to display premature repolarization at the 9th beat; by blocking 50% IKs with current stimuli at the interval 1000ms ; the action potential of I1768V began to display premature repolarization at the 3th beat; by blocking 40% IKs with current stimuli at the interval 1500ms ; the action potential of I1768V began to display premature repolarization at the 6th beat . 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.
In future work, in order to study whether the simulated premature repolarization may cause arrhythmia, a PC-Cluster capable of parallel computing will be set up to build a model of 2-dimensional heart to construct simulated electrocardiographs.
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