Ca<sub>v1.2</sub>离子通道马尔科夫随机过程模型的建立与应用

宋璟波; 张镇西

doi:10.7652/xjtuxb201802022

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Ca_v1.2离子通道马尔科夫随机过程模型的建立与应用

更新时间：2025-07-09

- Ca_v1.2离子通道马尔科夫随机过程模型的建立与应用
- Modeling and Applications of Markov Stochastic Process of Ca_v1.2 Ion Channel
- 西安交通大学学报 2018年52卷第2期页码：140-147
- 作者机构：
  
  西安交通大学生物医学信息工程教育部重点实验室,西安,710049
- 作者简介：
- 基金信息：
  
  : 2017-06-19。作者简介: 宋璟波(1982—),男,博士生;张镇西(通信作者),男,教授,博士生导师。基金项目: 国家自然科学基金资助项目(61335012,61727823)
- DOI：10.7652/xjtuxb201802022
  中图分类号： Q424;O211.62
- 网络首发：2018-02-10，
  
  纸质出版：2018
- 稿件说明：
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宋璟波, 张镇西. Ca_v1.2离子通道马尔科夫随机过程模型的建立与应用[J]. 西安交通大学学报, 2018,52(2):140-147. DOI: 10.7652/xjtuxb201802022.

Modeling and Applications of Markov Stochastic Process of Ca_v1.2 Ion Channel[J]. 2018, 52(2): 140-147. DOI: 10.7652/xjtuxb201802022.
宋璟波, 张镇西. Ca_v1.2离子通道马尔科夫随机过程模型的建立与应用[J]. 西安交通大学学报, 2018,52(2):140-147. DOI: 10.7652/xjtuxb201802022. DOI：

Modeling and Applications of Markov Stochastic Process of Ca_v1.2 Ion Channel[J]. 2018, 52(2): 140-147. DOI: 10.7652/xjtuxb201802022. DOI：

摘要

针对Ca

v1.2

离子通道在功能细胞的Ca

代谢循环中起着关键作用

并且在细胞交互环境下受到多种因素的调控从而表现出的复杂门控行为

基于现有的Ca

v1.2

结构信息

提出了改进的连续时间7态马尔科夫随机过程模型。首先抽象出7个通道状态来表征Ca

v1.2

离子通道的有限构象变化

包括电压相关失活(VDI)和Ca

相关失活(CDI); 其次应用相关实验数据求解7个状态间迁移速率函数的参数

即在贝叶斯框架下利用JAGS软件包

实现蒙特卡洛马尔可夫链(MCMC)算法对参数的后验分布进行Gibbs抽样。最后

将通道随机模型分别应用于描述小空间中Ca

瞬态行为的随机偏微分方程和Ca

v1.2

离子通道G406R/G432N突变引发的电生理变化。计算结果表明:改进的Ca

v1.2

马尔科夫模型不仅在宏观水平上与广泛的电生理实验结果有较好的吻合

而且在心肌细胞微结构以及通道基因的病理研究领域中具有较好的预测性。

Abstract

An improved seven states Markov stochastic process model based on current channel structure information is proposed to elucidate and forecast Ca

v1.2

complex gating kinetic in the interactive cell environment regulated by multiple factors which plays a key role in the Ca

metabolic cycle in functioning cells. Seven states are abstracted to present the limited conformational changes of Ca

v1.2

channel including VDI and CDI. Based on the Bayesian framework

the experiment data are then used to estimate the parameters of rate function between seven states via JAGS

which im

plements MCMC algorithm Gibbs sampler to sample the posterior distribution. The stochastic model is applied separately to stochastic PDEs profiling the Ca

transient in the subspace and the changed electrophysiological behavior induced by the channel mutations G406R/G432N. The computational results show that the improved Ca

v1.2

Markov framework coincides well with the broad electrophysiological observations at the macroscopic level

and it also has a better predictability in the field of cardiomyocytes microstructure and channel genes pathology.

关键词

Keywords

references

SOELLER C, CANNELL M B. Examination of the transverse tubular system in living cardiac rat myocytes by 2-photon microscopy and digital image processing techniques [J]. Circulation Research, 1999, 84(3): 266-275.

NOBLE D. Modeling the heart-from genes to cells to the whole organ [J]. Science, 2002, 295(5560): 1678-1682.

LUO C H, RUDY Y. A dynamic model of the cardiac ventricular action potential: I Simulations of ionic currents and concentration changes [J]. Circulation Research, 1994, 74(6): 1071-1096.

COLQUHOUN D, HAWKES A G. On the stochastic properties of bursts of single ion channel openings and of clusters of bursts [J]. Philosophical Transactions of the Royal Society: B Biological Sciences, 1982, 300(1098): 1-59.

MOROTTI S, GRANDI E, SUMMA A, et al. Theoretical study of L-type Ca2+ current inactivation kinetics during action potential repolarization and early afterdepolarizations [J]. J Physiol, 2012, 590(18): 4465-4481.

MAHAJAN A, SHIFERAW Y, SATO D, et al. A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates [J]. Biophys J, 2008, 94(2): 392-410.

BEZANILLA F. The voltage sensor in voltage-dependent ion channels [J]. Physiol Rev, 2000, 80(2): 555-592.

GAUTHIER L D, GREENSTEIN J L, WINSLOW R L. Toward an integrative computational model of the Guinea pig cardiac myocyte [J]. Front Physiol, 2012, 3: 244.

CAVALIE A, PELZER D, TRAUTWEIN W. Fast and slow gating behaviour of single calcium channels in cardiac cells: relation to activation and inactivation of calcium-channel current [J]. Pflugers Arch, 1986, 406(3): 241-258.

CENS T, ROUSSET M, LEYRIS J P, et al. Voltage-and calcium-dependent inactivation in high voltage-gated Ca(2+)channels [J]. Prog Biophys Mol Biol, 2006, 90(1/2/3): 104-117.

BENITAH J P, ALVAREZ J L, GMEZ A M. L-type Ca2+ current in ventricular cardiomyocytes [J]. Journal of Molecular and Cellular Cardiology, 2010, 48(1): 26-36.

FERREIRA G, YI J X, RIOS E, et al. Ion-dependent inactivation of barium current through L-type calcium channels [J]. Journal of General Physiology, 1997, 109(4): 449-461.

GRANDI E, MOROTTI S, GINSBURG K S, et al. Interplay of voltage and Ca-dependent inactivation of L-type Ca current [J]. Progress in Biophysics and Molecular Biology, 2010, 103(1): 44-50.

ZHONG J M, HWANG T C, ADAMS H R, et al. Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs [J]. American Journal of Physiology-Heart and Circulatory Physiology, 1997, 273(5): H2312-H2324.

REUTER H, STEVENS C F, TSIEN R W, et al. Properties of single calcium channels in cardiac cell culture [J]. Nature, 1982, 297(5866): 501-504.

SUN L, FAN J S, CLARK J W, et al. A model of the L-type Ca2+ channel in rat ventricular myocytes: ion selectivity and inactivation mechanisms [J]. The Journal of Physiology, 2000, 529(1): 139-158.

LANGER G A, PESKOFF A. Calcium concentration and movement in the diadic cleft space of the cardiac ventricular cell [J]. Biophys J, 1996, 70(3): 1169-1182.

SPLAWSKI I, TIMOTHY K W, SHARPE L M, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism [J]. Cell, 2004, 119(1): 19-31.

DEPIL K, BEYL S, STARY-WEINZINGER A, et al. Timothy mutation disrupts the link between activation and inactivation in Ca(V)1.2 protein [J]. J Biol Chem, 2011, 286(36): 31557-31564.

SPLAWSKI I, TIMOTHY K W, DECHER N, et al. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations [J]. Proc Natl Acad Sci USA, 2005, 102(23): 8089-8096.

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Cav1.2离子通道马尔科夫随机过程模型的建立与应用

Modeling and Applications of Markov Stochastic Process of Cav1.2 Ion Channel

DOI：10.7652/xjtuxb201802022

摘要

Abstract

关键词

Keywords

references

Ca_v1.2离子通道马尔科夫随机过程模型的建立与应用

Modeling and Applications of Markov Stochastic Process of Ca_v1.2 Ion Channel