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Accuracy considerations for capacitance estimation by voltage steps in cardiomyocytes
Progress in Biophysics and Molecular Biology ( IF 3.2 ) Pub Date : 2020-03-23 , DOI: 10.1016/j.pbiomolbio.2020.03.001
Dieter Platzer 1 , Klaus Zorn-Pauly 1
Affiliation  

Electrophysiologists routinely use simple voltage steps to evaluate cell membrane capacitance derived from corresponding current responses. Frequently, the resting membrane voltage Vrest is employed as holding potential for the subsequent command voltage step and more or less accurate methods are utilised to analyse the transient current. Another choice as holding potential is the peak of the “quasi steady-state” current to voltage relationship, Vpeak. The aim of this study is the systematic evaluation of capacitance estimation accuracy from voltage step experiments depending on the choice of holding potential and analysis method. In this paper, a simulation approach is employed to analyse the current response of a model patch-clamp circuit. Four commonly accepted methods are implemented, utilizing different aspects of the transient current (charge, membrane time constant, and influence of the series resistance) in various combinations and with various degrees of refinement. This simulation study indicates an acceptable accuracy of the elaborated methods for capacitance estimation at holding potentials Vrest and Vpeak over a broad range of capacitance as well as series resistance values.

Simple integration of the current transient provides sufficient accuracy at holding potentials, which effectively minimizes changes in resistive membrane current flow during command voltage steps (particularly around Vpeak). However, biphasic command protocols performed at Vpeak activate voltage dependent sodium channels, thereby possibly leading to the threshold voltage for an action potential. Compared to Vrest, all methods utilizing monophasic step protocols, gain additional accuracy, when applied at Vpeak as holding potential.



中文翻译:

心肌细胞中通过电压阶跃估算电容的精度考虑

电生理学家通常使用简单的电压步骤来评估从相应的电流响应得出的细胞膜电容。通常,静息膜电压V其余被用作保持电位为后续命令电压步骤和更多或更少的精确的方法被用来分析瞬变电流。保持电位的另一种选择是“准稳态”电流与电压的关系的峰值V peak。本研究的目的是根据保持电位的选择和分析方法,通过电压阶跃实验对电容估计精度进行系统评估。在本文中,采用一种仿真方法来分析模型膜片钳电路的电流响应。实现了四种公认的方法,这些方法以各种组合和不同程度的细化利用了瞬态电流的不同方面(电荷,膜时间常数和串联电阻的影响)。该仿真研究表明,在大范围的电容以及串联电阻值下,在保持电势V restV peak时,用于电容估计的详细方法的准确性是可以接受的。

电流瞬变的简单积分可在保持电势时提供足够的精度,从而有效地最大程度地减小了指令电压阶跃期间(尤其是在V peak附近)电阻膜电流的变化。但是,在V峰值处执行的双相命令协议会激活电压依赖性钠通道,从而可能导致动作电位的阈值电压。与V rest相比,当在V peak上用作保持电势时,所有利用单相步进协议的方法都可以获得更高的精度。

更新日期:2020-03-23
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