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Accounting for cardiac t-tubule increase with age and myocyte volume to improve measurements of its membrane area and ionic current densities.
Progress in Biophysics and Molecular Biology ( IF 3.8 ) Pub Date : 2020-08-10 , DOI: 10.1016/j.pbiomolbio.2020.06.005
Georges Christé 1 , Robert Bonvallet 2 , Christophe Chouabe 3
Affiliation  

In-silico models of cardiac myocytes allow simulating experiments in numbers on series of myocytes as well as on large populations of myocytes assembled in 3D structures. The simulated myocyte populations should have realistic values and statistical dispersions of biophysical parameters such as myocyte dimensions and volume and areas of the peripheral membrane and transverse-axial tubular system (TATS). Dependencies among these variables also have to be taken into account. In this work, we propose a quantitative representation of the changes in the fraction of membrane area in the TATS that integrates published dependencies with body weight (age) and size of rat ventricular cardiac myocytes while respecting the above constraints. Imposing a constant total membrane area-to-volume ratio appears to account for the increase of this fraction with myocyte size (i.e.: volume) within a given age group. The agreement of our results with published data was discussed and reasons for discrepancies were analysed. On the basis of our framework, strategies are proposed for minimizing the influence of non-random dispersion related to myocyte volume on measurements of the area of TATS and surface membrane compartments and of ionic current densities. The next step will be to quantitatively compare these strategies by evaluating the impact of myocyte morphological parameters and their dependencies, sample size, biases and errors, on the output of experiments.



中文翻译:

考虑到心脏T小管随年龄和心肌细胞体积的增加而增加,以改善其膜面积和离子电流密度的测量值。

硅内心肌细胞模型可以对一系列的心肌细胞以及以3D结构组装的大量心肌细胞进行模拟实验。模拟的肌细胞群体应具有现实价值和生物物理参数的统计分散,例如肌细胞的大小,外周膜和横轴管状系统(TATS)的体积和面积。这些变量之间的依赖性也必须考虑在内。在这项工作中,我们提出了TATS中膜面积分数变化的定量表示,该变化将已公布的依赖性与体重(年龄)和大鼠心室心肌细胞的大小整合在一起,同时考虑到上述限制。在给定年龄组中,施加恒定的总膜面积体积比似乎可以解释该分数随肌细胞大小(即体积)的增加。讨论了我们的结果与公开数据的一致性,并分析了差异的原因。根据我们的框架,提出了将与肌细胞体积有关的非随机分散对TATS和表面膜区室面积以及离子电流密度的测量影响最小化的策略。下一步将通过评估心肌细胞形态参数及其依赖性,样本量,偏倚和误差对实验输出的影响来定量比较这些策略。讨论了我们的结果与公开数据的一致性,并分析了差异的原因。根据我们的框架,提出了将与肌细胞体积有关的非随机分散对TATS和表面膜区室面积以及离子电流密度的测量影响最小化的策略。下一步将通过评估心肌细胞形态参数及其依赖性,样本量,偏倚和误差对实验输出的影响来定量比较这些策略。讨论了我们的结果与公开数据的一致性,并分析了差异的原因。根据我们的框架,提出了将与肌细胞体积有关的非随机分散对TATS和表面膜区室面积以及离子电流密度的测量影响最小化的策略。下一步将通过评估心肌细胞形态参数及其依赖性,样本量,偏倚和误差对实验输出的影响来定量比较这些策略。

更新日期:2020-08-10
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