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Kernel Based Non-Iterative Automatic Fast Capacitance Compensation in Patch-Clamp Experiments

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Abstract

Patch-clamp recording is a widely used technique for studying ion channel functions and cellular responses. During patch-clamp experiments, the fast capacitance (CFast) transient is a detrimental artifact and must be eliminated with CFast compensation circuit. When applying the conventional computer-aided CFast compensation procedure, the patch-clamp amplifier faces the risk of saturation due to large square-wave responses, and compensation errors may be caused due to inherent disadvantages of iterative algorithm. Here, we introduce a novel non-iterative automatic CFast compensation method, namely K-method, based on kernel estimation with white noise excitation. The kernel was estimated with cross-correlation technique and captured dynamic properties of the CFast and its related hardware. To achieve the optimal settings of the CFast compensation, the kernel of CFast was fitted to two calibrated kernels indicating two distinct types of compensation effect: the “instantaneous” and “delay” effect. The fitted coefficients were used to adjust compensation circuit. White noise excitation significantly reduced the possibility of saturation, and the K-method suffered from no typical disadvantage of iterative method. We performed compensation experiments on a model circuit and HEK293 cells. The results demonstrated a good accuracy of the K-method and the membrane capacitance measurement could benefit from it.

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References

  1. Hamill, O. P., A. Marty, E. Neher, B. Sakmann, and F. J. Sigworth. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 391:85–100, 1981.

    Article  Google Scholar 

  2. Marmarelis, V. Z. Nonlinear Dynamic Modeling of Physiological Systems. New Jersey: Wiley, 541 pp, 2004.

  3. Marty, A., and E. Neher. Tight-seal whole-cell recording. In: Single-Channel Recording, edited by B. Sakmann, and E. Neher. New York: Plenum Press, 1995, pp. 31–52.

    Google Scholar 

  4. Press, W., S. Teukolsky, W. T. Vetterling, and B. Flannery. Numerical Recipes in C: the Art of Scientific Computing. New York: Cambridge University Press, 1235 pp., 2007.

  5. Sigworth, F. J. Design of the EPC-9, a computer-controlled patch-clamp amplifier. 1. Hardware. J. Neurosci. Methods 56:195–202, 1995.

    Article  Google Scholar 

  6. Sigworth, F. J., H. Affolter, and E. Neher. Design of the EPC-9, a computer-controlled patch-clamp amplifier. 2. Software. J. Neurosci. Methods 56:203–215, 1995.

    Article  Google Scholar 

  7. Xiong, J., G. Hu, and A. Qu. Automatic calibration of frequency compensation system in computer-controlled patch-clamp amplifier. J. Comp. Sci. 3:765–772, 2007.

    Article  Google Scholar 

  8. Ye, Y., G. Hu, and A. Qu. The improvement of C-Fast transient cancellation in automatic patch-clamp amplifier. Shanghai J. Biomed. Eng. 27:98–101, 2006.

    Google Scholar 

  9. Zhang, H., J. Luo, J. Xiong, X. G. Lin, Z. X. Wu, and A. Qu. Zf-and-Hsys-based Cm measurement under the whole-cell patch-clamp recording. Pflugers Arch. 457:1423–1434, 2009.

    Article  Google Scholar 

  10. Zhang, H., A. Qu, J. Luo, and J. Luo. Error analysis of Cm measurement under the whole-cell patch-clamp recording. J. Neurosci. Methods 185:307–314, 2010.

    Article  Google Scholar 

  11. Zhang, H., J. Xiong, J. Luo, and A. Qu. Experimental determination of Cm measurement related hardware parameters of the patch-clamp amplifier. J. Neurosci. Methods. 176:246–253, 2009.

    Article  Google Scholar 

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Acknowledgments

We thank Haowen Liu for his efforts and patience in the experiments. This work was supported by grants from National Nature Science Foundation of China (No. 30327001).

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The authors have declared that no conflict of interest exists.

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Correspondence to Jiuping Ding or Anlian Qu.

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Associate Editor Edward Guo oversaw the review of this article.

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Luo, J., Hou, P., Ding, J. et al. Kernel Based Non-Iterative Automatic Fast Capacitance Compensation in Patch-Clamp Experiments. Cel. Mol. Bioeng. 5, 440–449 (2012). https://doi.org/10.1007/s12195-012-0241-z

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