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Causes of Transient Instabilities in the Dynamic Clamp

机译:动态钳位电路中瞬态不稳定的原因

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摘要

The dynamic clamp is a widely used method for integrating mathematical models with electrophysiological experiments. This method involves measuring the membrane voltage of a cell, using it to solve computational models of ion channel dynamics in real-time, and injecting the calculated current(s) back into the cell. Limitations of this technique include those associated with single electrode current clamping and the sampling effects caused by the dynamic clamp. In this study, we show that the combination of these limitations causes transient instabilities under certain conditions. Through physical experiments and simulations, we show that dynamic clamp instability is directly related to the sampling delay and the maximum simulated conductance being injected. It is exaggerated by insufficient electrode series resistance and capacitance compensation. Increasing the sampling rate of the dynamic clamp system increases dynamic clamp stability; however, this improvement, is constrained by how well the electrode series resistance and capacitance are compensated. At present, dynamic clamp sampling rates are justified solely on the temporal dynamics of the models being simulated; here we show that faster rates increase the stable range of operation for the dynamic clamp system. In addition, we show that commonly accepted levels of resistance compensation nevertheless significantly compromise the stability of a dynamic clamp system.
机译:动态钳位是将数学模型与电生理实验集成在一起的一种广泛使用的方法。该方法涉及测量电池的膜电压,使用它实时求解离子通道动力学的计算模型,然后将计算出的电流注入到电池中。该技术的局限性包括与单电极电流钳制有关的局限性以及由动态钳制引起的采样效应。在这项研究中,我们表明这些限制的组合会在某些条件下导致瞬态不稳定。通过物理实验和仿真,我们表明动态钳位不稳定性与采样延迟和注入的最大模拟电导率直接相关。电极串联电阻和电容补偿不足会加剧这种情况。增加动态钳位系统的采样率可提高动态钳位的稳定性;但是,这种改进受到电极串联电阻和电容补偿程度的限制。目前,动态钳位采样率仅根据所模拟模型的时间动态是合理的。在这里,我们显示出更快的速率可以增加动态钳位系统的稳定工作范围。此外,我们表明,公认的电阻补偿水平仍然显着损害了动态钳位系统的稳定性。

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  • 期刊名称 other
  • 作者单位
  • 年(卷),期 -1(17),2
  • 年度 -1
  • 页码 190–198
  • 总页数 20
  • 原文格式 PDF
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