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Native gating behavior of ion channels in neurons with null-deviation modeling

PLoS One. 2013 Oct 25;8(10):e77105. doi: 10.1371/journal.pone.0077105. eCollection 2013.

Abstract

Computational modeling has emerged as an indispensable approach to resolve and predict the intricate interplay among the many ion channels underlying neuronal excitability. However, simulation results using the classic formula-based Hodgkin-Huxley (H-H) model or the superior Markov kinetic model of ion channels often deviate significantly from native cellular signals despite using carefully measured parameters. Here we found that the filters of patch-clamp amplifier not only delayed the signals, but also introduced ringing, and that the residual series resistance in experiments altered the command voltages, which had never been fully eliminated by improving the amplifier itself. To remove all the above errors, a virtual device with the parameters exactly same to that of amplifier was introduced into Markov kinetic modeling so as to establish a null-deviation model. We demonstrate that our novel null-deviation approach fully restores the native gating-kinetics of ion-channels with the data recorded at any condition, and predicts spike waveform and firing patterns clearly distinctive from those without correction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Algorithms
  • Animals
  • CHO Cells
  • Computer Simulation
  • Cricetinae
  • Cricetulus
  • HEK293 Cells
  • Humans
  • Ion Channel Gating / physiology*
  • Ion Channels / metabolism
  • Ion Channels / physiology*
  • Membrane Potentials / physiology
  • Models, Neurological*
  • Neurons / metabolism
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Shaw Potassium Channels / metabolism
  • Shaw Potassium Channels / physiology

Substances

  • Ion Channels
  • Shaw Potassium Channels

Grants and funding

This work was supported by grants from the National Basic Research Program of China (2010CB529804), the National Science Foundation of China (30971179, 31170814, 31028006) (to JPD), and by individual Operating Grants from the Canadian Institutes of Health Research, China-Canada Joint Health Research Initiative Grant and Canada Research Chair (to LYW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.