心筋細胞活動電位シミュレーションを用いたQT延長メカニズムの検討
スポンサーリンク
概要
- 論文の詳細を見る
In heart failure, QT interval and action potential duration (APD) is prolonged and IKs, a slow component of delayed rectifier potassium current, decreases. We have reported that the KCNE1 gene, coding IKs channel, increases and QT interval is prolonged in patients with heart failure. Since it is known that increasing KCNE1 increases the maximum conductance of the IKs channel, the mechanism of APD prolongation is not explained by the over expression of KCNE1. In this study, we construct a cardiac membrane action potential simulation model based on the experimental data from oocytes expression to investigate the relationship between the increase of KCNE1 and APD. In the experiment of oocyte expression, 1 ng and 5 ng of KCNE1 were co-injected with 5 ng of KCNQ1. Expressed currents were recorded 1-2 days after injection by the double-microelectrode voltage clamp method at 35 degrees centigrade. Maximum IKs conductance and relationships between time constants, maximum activation parameter and membrane potential were obtained from fitting functions describing IKs channel properties in the Luo-Rudy model to experimental results with the Nelder-Mead simplex method. In simulations, APD was prolonged by increasing the co-injected amount of KCNE1. APD at 5 ng KCNE1 was 183 ms, which is 3.4% longer than that at 1 ng KCNE1 (APD=177 ms). This study shows that increasing the KCNE1 expression level makes maximum IKs conductance increase and IKs channel open slowly and IKs conductance 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 KCNE1 expression ratio and QT interval prolongation.
- 一般社団法人 日本生体医工学会の論文
一般社団法人 日本生体医工学会 | 論文
- Evaluating the Workload Reduction of Automatic Vital Data Transmission
- Mental Fatigue Measurement Based on the Changes in Flicker Perception Threshold using Consumer Mobile Devices
- A Theoretical Study on a Computational Algorithm for Human Posture Estimation Based on Motion Capture of a Small Number of Markers
- Latest microscopic technique. From the principle to application. Development of three-dimensional microscopic system for operation of mini-pig fertilized eggs.
- A Study of the Automation of Cytodiagnosis (The Second Report):Cytophotometry Using Photomicroscanner and a Trial of Data-processing