Preyer Amanda J, Butera Robert J
Georgia Institute of Technology, Atlanta, GA 30332, USA.
IEEE Trans Neural Syst Rehabil Eng. 2009 Apr;17(2):190-8. doi: 10.1109/TNSRE.2009.2015205. Epub 2009 Feb 18.
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.
动态钳是一种广泛应用于将数学模型与电生理实验相结合的方法。该方法包括测量细胞的膜电压，利用其实时求解离子通道动力学的计算模型，并将计算出的电流注入回细胞中。该技术的局限性包括与单电极电流钳相关的局限性以及动态钳引起的采样效应。在本研究中，我们表明这些局限性的组合在某些条件下会导致瞬态不稳定性。通过物理实验和模拟，我们表明动态钳不稳定性与采样延迟和注入的最大模拟电导直接相关。电极串联电阻和电容补偿不足会使其加剧。提高动态钳系统的采样率可提高动态钳稳定性；然而，这种改进受到电极串联电阻和电容补偿程度的限制。目前，动态钳采样率仅根据所模拟模型的时间动态来确定；在此我们表明更快的采样率会增加动态钳系统的稳定工作范围。此外，我们表明普遍接受的电阻补偿水平仍会显著损害动态钳系统的稳定性。
