Parameter estimation in cardiac ionic models
Parameter estimation in cardiac ionic models
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DOI：
10.1016/j.pbiomolbio.2004.02.002
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发表时间：
2004-06-01
影响因子：
3.8
通讯作者：
Lovell, NH
中科院分区：
文献类型：
--
作者：
Dokos, S;Lovell, NH
我们使用著名的Beeler-Reuters(1977)心室动作电位离子方程来研究可兴奋细胞心脏电活动的数学模型中的参数估计问题。该估计问题可以看作是在仅给出动作电位实验数据的情况下，在可激发细胞模型中准确地重建离子电流动力学和幅度的问题。我们发现，在Beeler-Reuters的情况下，所有的离子电流都可以用一个由伪随机注入电流扰动的动作电位记录组成的实验设计来合理地重建。Beeler-Reuters模型被参数化为63个参数，完全定义了所有的膜电流幅度和动力学。总的膜电流与模型生成的实验数据通过数据钳制协议进行了拟合。实验数据包括一个默认的动作电位波形和一系列可选的由电流注入产生的扰动波形。根据已知解的黑森倒数条件值(1/lambda)确定局部参数可辨识性。当符合单个动作电位波形时，该模型被发现是过度确定的，其1/lambda值类似于3.6e-14。当在拟合过程中包括另外两个扰动波形时，这个值略有改善，接近1.4e-10，这表明额外的数据并没有过度改善可识别性问题。然而，额外的数据确实允许准确地重建所有的离子流。这表明，通过适当的实验设计，可以通过观察受伪随机电流扰动的跨膜电位波形来推断潜在的膜电流的特性。(C)2004爱思唯尔有限公司。保留所有权利。
We examine the problem of parameter estimation in mathematical models of excitable cell cardiac electrical activity using the well-known Beeler-Reuter (1977) ionic equations for the ventricular action potential. The estimation problem can be regarded as equivalent to the accurate reconstruction of ionic current kinetics and amplitudes in an excitable cell model, given only action potential experimental data. We show that in the Beeler-Reuter case, all ionic currents may be reasonably reconstructed using an experimental design consisting of action potential recordings perturbed by pseudo-random injection currents.The Beeler-Reuter model was parameterised into 63 parameters completely defining all membrane current amplitudes and kinetics. Total membrane current was fitted to model-generated experimental data using a 'data-clamp' protocol. The experimental data consisted of a default action-potential waveform and an optional series of perturbed waveforms generated by current injections. Local parameter identifiability was ascertained from the reciprocal condition value (1/lambda) of the Hessian at the known solution. When fitting to a single action potential waveform, the model was found to be over-determined, having a 1/lambda value of similar to3.6e-14. This value improved slightly to similar to1.4e-10 when an additional 2 perturbed waveforms were included in the fitting process, suggesting that the additional data did not overly improve the identifiability problem. The additional data, however, did allow the accurate reconstruction of all ionic currents. This indicates that by appropriate experimental design, it may be possible to infer the properties of underlying membrane currents from observation of transmembrane potential waveforms perturbed by pseudo-random currents. (C) 2004 Elsevier Ltd. All rights reserved.