Analysis of QT interval prolongation with heart failure by simulation of repolarization process

T. Yamaguchi, T. Arafune, I. Sakuma, E. Watanabe, N. Shibata, H. Honjo, I. Kodama, K. Kamiya

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

It has been postulated that action potential duration (APD) is prolonged and IKs, a slow component of delayed rectifier potassium current, decreases in heart failure. We have reported that QT interval is prolonged and expression weight of KCNE1, coding IKs channel, increases in patients with heart failure. Since it is known that increase in KCNE1 increases the maximum conductance of IKs channel, the mechanism of APD prolongation is not explained by over expression of KCNE1. In this study, we construct a cardiac membrane action potential simulation model based on the experimental data from Xenopus oocytes expressed KCNQ1 and KCNE1 to investigate the relationship between increase in KCNE1 and APD, In addition, we investigated effect of reduction in Ca2+-independent transient outward potassium current (Ito) on APD in heart failure. In simulation, APD at 5ng KCNE1 was 180.96ms, which was 4.63% longer than that at Ing KCNE1 (APD=172.96ms) and 55.9% longer than that at 0.2ng KCNE1 (APD=110.96ms). In the cases of KCNQ1 alone and 0.2ng KCNE1 coinjected, APD shortened as density of Ito decreased, and APD prolonged as density of Ito decreased in other cases. This study shows that increase in KCNE1 expression level makes maximum conductance of IKs channel increase and IKs channel open slowly and conductance of IKs channel decrease according to the APD time scale. Therefore increasing the KCNE1 expression level may prolong APD with this mechanism. This method of constructing a simulation model based on experiments helps to explain the relationship between potassium currents and QT interval prolongation.

Original languageEnglish
Title of host publicationProceedings of the 2005 27th Annual International Conference of the Engineering in Medicine and Biology Society, IEEE-EMBS 2005
Pages7309-7312
Number of pages4
Publication statusPublished - 01-12-2005
Event2005 27th Annual International Conference of the Engineering in Medicine and Biology Society, IEEE-EMBS 2005 - Shanghai, China
Duration: 01-09-200504-09-2005

Publication series

NameAnnual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume7 VOLS
ISSN (Print)0589-1019

Other

Other2005 27th Annual International Conference of the Engineering in Medicine and Biology Society, IEEE-EMBS 2005
CountryChina
CityShanghai
Period01-09-0504-09-05

All Science Journal Classification (ASJC) codes

  • Signal Processing
  • Biomedical Engineering
  • Computer Vision and Pattern Recognition
  • Health Informatics

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    Yamaguchi, T., Arafune, T., Sakuma, I., Watanabe, E., Shibata, N., Honjo, H., Kodama, I., & Kamiya, K. (2005). Analysis of QT interval prolongation with heart failure by simulation of repolarization process. In Proceedings of the 2005 27th Annual International Conference of the Engineering in Medicine and Biology Society, IEEE-EMBS 2005 (pp. 7309-7312). [1616199] (Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings; Vol. 7 VOLS).