Identifying Drug Response by Combining Measurements of the Membrane Potential, the Cytosolic Calcium Concentration, and the Extracellular Potential in Microphysiological Systems.
Identifying Drug Response by Combining Measurements of the Membrane Potential, the Cytosolic Calcium Concentration, and the Extracellular Potential in Microphysiological Systems.
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DOI：
10.3389/fphar.2020.569489
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发表时间：
2020
影响因子：
5.6
通讯作者：
Tveito A
中科院分区：
文献类型：
--
作者：
Jæger KH;Charwat V;Wall S;Healy KE;Tveito A
来源于人类诱导多能干细胞的心肌细胞(hiPSC-CMS)为研究和理解人类心脏动作电位提供了新的手段，并可以为化合物如何与破坏心脏电功能稳定的重要分子途径相互作用提供关键的见解。动作电位的重要特征可以很容易地使用标准的实验技术来测量，例如使用电压敏感染料和荧光遗传报告来估计跨膜电位和细胞内钙浓度。使用以前介绍的计算程序，这种测量可以用来估计HiPSC-CMS中存在的主要离子通道的电流密度，以及化合物可能如何改变它们的行为。然而，由于光学记录的局限性，从这些数据中解析钠电流仍然是困难的。在这里，我们表明，如果这些光学测量与使用多电极阵列(MEA)对细胞外电位的观察相补充，我们可以准确地估计钠通道的电流密度。钠电流的这种反转依赖于对传导速度的观察，而传导速度是通过测量电极上的细胞外波直接计算出来的。包括膜电位、细胞内钙离子浓度和细胞外电位在内的联合数据进一步为准确评估新药应用于HiPSC-CMS的效果提供了可能性。
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) offer a new means to study and understand the human cardiac action potential, and can give key insight into how compounds may interact with important molecular pathways to destabilize the electrical function of the heart. Important features of the action potential can be readily measured using standard experimental techniques, such as the use of voltage sensitive dyes and fluorescent genetic reporters to estimate transmembrane potentials and cytosolic calcium concentrations. Using previously introduced computational procedures, such measurements can be used to estimate the current density of major ion channels present in hiPSC-CMs, and how compounds may alter their behavior. However, due to the limitations of optical recordings, resolving the sodium current remains difficult from these data. Here we show that if these optical measurements are complemented with observations of the extracellular potential using multi electrode arrays (MEAs), we can accurately estimate the current density of the sodium channels. This inversion of the sodium current relies on observation of the conduction velocity which turns out to be straightforwardly computed using measurements of extracellular waves across the electrodes. The combined data including the membrane potential, the cytosolic calcium concentration and the extracellular potential further opens up for the possibility of accurately estimating the effect of novel drugs applied to hiPSC-CMs.
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影响因子：
4.6
作者：
Raphel, Fabien;Boulakia, Muriel;Gerbeau, Jean-Frederic
通讯作者：
Gerbeau, Jean-Frederic
影响因子：
4.6
作者：
Mathur A;Loskill P;Shao K;Huebsch N;Hong S;Marcus SG;Marks N;Mandegar M;Conklin BR;Lee LP;Healy KE
通讯作者：
Healy KE
DOI：
10.1007/978-3-319-04801-7
发表时间：
2014-01-01
期刊：
MATHEMATICAL CARDIAC ELECTROPHYSIOLOGY
影响因子：
--
作者：
Franzone, P. C.;Pavarino, L. F.;Scacchi, S.
通讯作者：
Scacchi, S.
DOI：
10.1016/j.vascn.2016.03.009
发表时间：
2016-09-01
影响因子：
1.9
作者：
Crumb, William J., Jr.;Vicente, Jose;Strauss, David G.
通讯作者：
Strauss, David G.
影响因子：
16.1
作者：
Mathur A;Ma Z;Loskill P;Jeeawoody S;Healy KE
通讯作者：
Healy KE