Journal
IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
Volume 17, Issue 2, Pages 190-198Publisher
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
DOI: 10.1109/TNSRE.2009.2015205
Keywords
Action potential; biological cells; control systems; nervous system
Categories
Funding
- National Institutes of Health [R01-RR20115]
- Weill Medical College of Cornell University [R01-NS054281]
- LSU Health Science Center
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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.
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