Identification of structures for ion channel kinetic models.
Identification of structures for ion channel kinetic models.
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离子通道动力学模型的结构鉴定。
DOI：
10.1371/journal.pcbi.1008932
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发表时间：
2021-08
影响因子：
4.3
通讯作者：
Silva JR
中科院分区：
文献类型：
--
作者：
Mangold KE;Wang W;Johnson EK;Bhagavan D;Moreno JD;Nerbonne JM;Silva JR
马尔可夫模型的离子通道动力学的发展，实验的进展，提高了我们的理解通道功能。过去的研究已经研究了有限的各种拓扑结构的马尔可夫模型的信道动态。我们提出了一个系统的方法来识别所有可能的马尔可夫模型拓扑结构使用实验数据的两种类型的本地电压门控离子通道电流：小鼠心房钠电流和人左心室快速瞬态外向钾电流。用这种方法确定的成功模型具有某些共同的特征，这表明模型拓扑结构的各个方面是由实验数据决定的。将这些通道模型扩展到细胞和组织模拟中以评估未用于训练的方案内的模型性能提供了验证并进一步缩小了可接受模型的数量。这种方法的成功表明，在模型的结构未被先验指定的情况下，信道模型创建流水线可能是可行的。马尔可夫模型的离子通道动力学的发展，实验的进展，提高了我们的理解通道功能。过去的研究已经检查了信道动态马尔可夫模型的各种结构的有限集合。在这里，我们提出了一个计算程序，旨在彻底搜索马尔可夫模型拓扑结构模拟全细胞电流。我们在两种不同类型的电压门控心脏离子通道上测试了这种方法，并发现了概括实验观察到的动力学所需的状态和连接的数量。用这种方法确定的成功模型具有某些共同的特征，这表明模型结构是由实验数据决定的。将这些模型纳入更高尺度的动作电位和电缆（一维动作电位传播的近似）模拟，确定了正确功能所需的关键通道现象。这些方法提供了一种创建可用于动作电位模拟的功能通道模型的途径，而无需提前预定义其结构。
Markov models of ion channel dynamics have evolved as experimental advances have improved our understanding of channel function. Past studies have examined limited sets of various topologies for Markov models of channel dynamics. We present a systematic method for identification of all possible Markov model topologies using experimental data for two types of native voltage-gated ion channel currents: mouse atrial sodium currents and human left ventricular fast transient outward potassium currents. Successful models identified with this approach have certain characteristics in common, suggesting that aspects of the model topology are determined by the experimental data. Incorporating these channel models into cell and tissue simulations to assess model performance within protocols that were not used for training provided validation and further narrowing of the number of acceptable models. The success of this approach suggests a channel model creation pipeline may be feasible where the structure of the model is not specified a priori. Markov models of ion channel dynamics have evolved as experimental advances have improved our understanding of channel function. Past studies have examined limited sets of various structures for Markov models of channel dynamics. Here, we present a computational routine designed to thoroughly search for Markov model topologies for simulating whole-cell currents. We tested this method on two distinct types of voltage-gated cardiac ion channels and found the number of states and connectivity required to recapitulate experimentally observed kinetics. Successful models identified with this approach have certain characteristics in common, suggesting that model structures are determined by the experimental data. Incorporation of these models into higher scale action potential and cable (an approximation of one-dimensional action potential propagation) simulations, identified key channel phenomena that were required for proper function. These methods provide a route to create functional channel models that can be used for action potential simulation without pre-defining their structure ahead of time.
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影响因子：
5.3
作者：
Lee, SY;Lee, KG
通讯作者：
Lee, KG
DOI：
10.1073/pnas.0409110102
发表时间：
2005-05-03
影响因子：
11.1
作者：
Bruno, WJ;Yang, J;Pearson, JE
通讯作者：
Pearson, JE
DOI：
10.1085/jgp.201611678
发表时间：
2017-03-06
期刊：
The Journal of general physiology
影响因子：
--
作者：
Hsu EJ;Zhu W;Schubert AR;Voelker T;Varga Z;Silva JR
通讯作者：
Silva JR
影响因子：
56.9
作者：
Jensen, Morten O.;Jogini, Vishwanath;Shaw, David E.
通讯作者：
Shaw, David E.
影响因子：
3.4
作者：
Lei, Chon Lok;Clerx, Michael;Wang, Ken
通讯作者：
Wang, Ken