Description of the Human Atrial Action Potential Derived From a Single, Congruent Data Source: Novel Computational Models for Integrated Experimental-Numerical Study of Atrial Arrhythmia Mechanisms.
Description of the Human Atrial Action Potential Derived From a Single, Congruent Data Source: Novel Computational Models for Integrated Experimental-Numerical Study of Atrial Arrhythmia Mechanisms.
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DOI：
10.3389/fphys.2018.01211
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发表时间：
2018
影响因子：
4
通讯作者：
Workman AJ
中科院分区：
文献类型：
--
作者：
Colman MA;Saxena P;Kettlewell S;Workman AJ
简介：人类房颤（AF）的诊断、管理和治疗策略的改进是一项重大而重要的挑战，可以改善数百万人的生活质量，降低疾病的社会经济成本。作为一种表现出高变异性并与其他心脏疾病相关的复杂疾病，AF的研究需要多个学科的方法，包括单细胞实验电生理学和计算建模。人心房细胞的模型比人心室或其他哺乳动物物种的模型参数化得更差，这主要是由于膜片钳人心房细胞的固有挑战。这些挑战通常包括非生理性去极化静息电位，从而注入补偿性超极化电流，以及检测可能被细胞分离过程破坏的某些离子电流。本研究的目的是开发一种实验室特定的人类心房电生理学模型，该模型可以精确再现分离细胞实验的条件，包括多种实验干预的测试。研究方法：在Workman实验室中通过隔离细胞实验表征的初级离子电流的配方直接拟合电压钳数据;基于将静息膜电位与最大动作电位上升速度相关的实验，对快速钠电流进行参数化;包括补偿超极化电流作为恒定施加电流。将这些制剂与三种独立的人心房细胞模型整合，以提供一系列新模型。通过去除超极化电流和引入终末复极钾电流，建立了外推的完整细胞模型。结果如下：分离的细胞模型定量再现实验测量的兴奋在控制和药理学和动态钳干预的属性。隔离和完整的细胞模型的比较强调了复制这种细胞环境的重要性，比较实验和模拟数据时。结论：我们已经开发了一个实验室特定的模型，人类心房细胞直接再现实验隔离细胞的条件下，并捕捉人类心房兴奋特性。该模型可能是特别有用的直接相关的模型实验，并提供了一个补充工具，以可用的一组人类心房细胞模型的特定优势，从全等输入数据源。
Introduction: The development of improved diagnosis, management, and treatment strategies for human atrial fibrillation (AF) is a significant and important challenge in order to improve quality of life for millions and reduce the substantial social-economic costs of the condition. As a complex condition demonstrating high variability and relation to other cardiac conditions, the study of AF requires approaches from multiple disciplines including single-cell experimental electrophysiology and computational modeling. Models of human atrial cells are less well parameterized than those of the human ventricle or other mammal species, largely due to the inherent challenges in patch clamping human atrial cells. Such challenges include, frequently, unphysiologically depolarized resting potentials and thus injection of a compensatory hyperpolarizing current, as well as detecting certain ion currents which may be disrupted by the cell isolation process. The aim of this study was to develop a laboratory specific model of human atrial electrophysiology which reproduces exactly the conditions of isolated-cell experiments, including testing of multiple experimental interventions. Methods: Formulations for the primary ion currents characterized by isolated-cell experiments in the Workman laboratory were fit directly to voltage-clamp data; the fast sodium-current was parameterized based on experiments relating resting membrane potential to maximal action potential upstroke velocity; compensatory hyperpolarizing current was included as a constant applied current. These formulations were integrated with three independent human atrial cell models to provide a family of novel models. Extrapolated intact-cell models were developed through removal of the hyperpolarizing current and introduction of terminal repolarization potassium currents. Results: The isolated-cell models quantitatively reproduced experimentally measured properties of excitation in both control and pharmacological and dynamic-clamp interventions. Comparison of isolated and intact-cell models highlighted the importance of reproducing this cellular environment when comparing experimental and simulation data. Conclusion: We have developed a laboratory specific model of the human atrial cell which directly reproduces the experimental isolated-cell conditions and captures human atrial excitation properties. The model may be particularly useful for directly relating model to experiment, and offers a complementary tool to the available set of human atrial cell models with specific advantages resulting from the congruent input data source.
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影响因子：
4
作者：
Colman MA;Perez Alday EA;Holden AV;Benson AP
通讯作者：
Benson AP
影响因子：
10.8
作者：
Kettlewell S;Burton FL;Smith GL;Workman AJ
通讯作者：
Workman AJ
心房颤动引起的电重塑的致心律失常效应：来自三维虚拟人体心房的见解
DOI：
10.1113/jphysiol.2013.254987
发表时间：
2013-09-01
期刊：
The Journal of physiology
影响因子：
--
作者：
Colman MA;Aslanidi OV;Kharche S;Boyett MR;Garratt C;Hancox JC;Zhang H
通讯作者：
Zhang H
DOI：
10.1016/s0735-1097(97)00385-9
发表时间：
1997-12-01
影响因子：
24
作者：
Franz, MR;Karasik, PL;Chavez, M
通讯作者：
Chavez, M
影响因子：
10.8
作者：
FIREK, L;GILES, WR
通讯作者：
GILES, WR