title: Native gating behavior of ion channels in neurons with null-deviation modeling.
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.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Panpan
authors.initials: P
authors.lastname: Hou
authors.forename: Yimei
authors.initials: Y
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Xiao
authors.forename: Ming
authors.initials: M
authors.lastname: Yuchi
authors.forename: Anlian
authors.initials: A
authors.lastname: Qu
authors.forename: Luyang
authors.initials: L
authors.lastname: Wang
authors.forename: Jiuping
authors.initials: J
authors.lastname: Ding
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000465:Algorithms; D000818:Animals; D016466:CHO Cells; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051670:Shaw Potassium Channels / Q000378:metabolism / Q000502:physiology
chemical_list: D007473:Ion Channels; D051670:Shaw Potassium Channels