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http://dx.doi.org/10.9718/JBER.2017.38.3.123

Correlation Analysis of KCNQ1 S140G Mutation Expression and Ventricular Fibrillation: Computer Simulation Study  

Jeong, Daun (Dept. of IT Convergence Engineering, Kumoh National Institute of Technology)
Lim, Ki Moo (Dept. of IT Convergence Engineering, Kumoh National Institute of Technology)
Publication Information
Journal of Biomedical Engineering Research / v.38, no.3, 2017 , pp. 123-128 More about this Journal
Abstract
Background and aims: The KCNQ1 S140G mutation involved in $I_{ks}$ channel is a typical gene mutation affecting atrial fibrillation. However, despite the possibility that the S140G gene mutation may affect not only atrial but also ventricular action potential shape and ventricular responses, there is a lack of research on the relationship between this mutation and ventricular fibrillation. Therefore, in this study, we analyzed the correlation and the influence of the KCNQ1 S140G mutant gene on ventricular fibrillation through computer simulation studies. Method: This study simulated a 3-dimensional ventricular model of the wild type(WT) and the S140G mutant conditions. It was performed by dividing into normal sinus rhythm simulation and reentrant wave propagation simulation. For the sinus rhythm, a ventricular model with Purkinje fiber was used. For the reentrant propagation simulation, a ventricular model was used to confirm the occurrence of spiral wave using S1-S2 protocol. Results: The result showed that 41% shortening of action potential duration(APD) was observed due to augmented $I_{ks}$ current in S140G mutation group. The shortened APD contributed to reduce wavelength 39% in sinus rhythm simulation. The shortened wavelength in cardiac tissue allowed re-entrant circuits to form and increased the probability of sustaining ventricular fibrillation, while ventricular electrical propagation with normal wavelength(20.8 cm in wild type) are unlikely to initiate re-entry. Conclusion: In conclusion, KCNQ1 S140G mutation can reduce the threshold of the re-entrant wave substrate in ventricular cells, increasing the spatial vulnerability of tissue and the sensitivity of the fibrillation. That is, S140G mutation can induce ventricular fibrillation easily. It means that S140G mutant can increase the risk of arrhythmias such as cardiac arrest due to heart failure.
Keywords
KCNQ1 S140G; ventricular fibrillation; action potential duration(APD); effective refractory period(ERP); $I_{ks}$; electrophysiology 3D model; sinus rhythm;
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