Abstract:
The L-type calcium current ( I CaL ) plays a critical role in cardiac electrophysiology, and models of I CaL are vital tools to predict arrhythmogenicity of drugs and mutations. Five decades of measuring and modeling I CaL have resulted in several competing theories (encoded in mathematical equations). However, the introduction of new models has not typically been accompanied by a data-driven critical comparison with previous work, so that it is unclear which model is best suited for any particular application. In this review, we describe and compare 73 published mammalian I CaL models and use simulated experiments to show that there is a large variability in their predictions, which is not substantially diminished when grouping by species or other categories. We provide model code for 60 models, list major data sources, and discuss experimental and modeling work that will be required to reduce this huge list of competing theories and ultimately develop a community consensus model of I CaL . This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Molecular and Cellular Physiology.
摘要:
L型钙电流(ICaL)在心脏电生理中起关键作用,和ICaL模型是预测药物和突变的心律失常性的重要工具。经过五十年的测量和建模,ICaL产生了几种相互竞争的理论(用数学方程式编码)。然而,新模型的引入通常没有伴随着与以前工作的数据驱动的关键比较,因此,尚不清楚哪种模型最适合任何特定应用。在这次审查中,我们描述和比较了73个已发表的哺乳动物ICaL模型,并使用模拟实验来表明它们的预测存在很大的变异性,当按物种或其他类别分组时,这不会大大减少。我们提供了60个型号的型号代码,列出主要数据源,并讨论减少竞争理论的庞大清单并最终开发ICaL的社区共识模型所需的实验和建模工作。本文分为:心血管疾病>计算模型心血管疾病>分子和细胞生理学。