Ion Channel Modeling beyond State of the Art: A Comparison with a System Theory-Based Model of the Shaker-Related Voltage-Gated Potassium Channel Kv1.1

Sonja Langthaler, Jasmina Lozanovic Sajic, Theresa Margarethe Rienmüller, Seth Weinberg, Christian Baumgartner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The mathematical modeling of ion channel kinetics is an important tool for studying the electrophysiological mechanisms of the nerves, heart, or cancer, from a single cell to an organ. Com-mon approaches use either a Hodgkin–Huxley (HH) or a hidden Markov model (HMM) description, depending on the level of detail of the functionality and structural changes of the underlying channel gating, and taking into account the computational effort for model simulations. Here, we introduce for the first time a novel system theory-based approach for ion channel modeling based on the concept of transfer function characterization, without a priori knowledge of the biological system, using patch clamp measurements. Using the shaker-related voltage-gated potassium channel Kv1.1 (KCNA1) as an example, we compare the established approaches, HH and HMM, with the system theory-based concept in terms of model accuracy, computational effort, the degree of electrophysiological interpretability, and methodological limitations. This highly data-driven modeling concept offers a new opportunity for the phenomenological kinetic modeling of ion channels, exhibiting exceptional accuracy and computational efficiency compared to the conventional methods. The method has a high potential to further improve the quality and computational performance of complex cell and organ model simulations, and could provide a valuable new tool in the field of next-generation in silico electrophysiology.

Original languageEnglish
Article number239
Number of pages27
JournalCells
Volume11
Issue number2
DOIs
Publication statusPublished - 1 Jan 2022

Keywords

  • Computational model
  • Electrophysiology
  • Hidden Markov model
  • Hodgkin–Huxley
  • Ion channels
  • System and control theory

ASJC Scopus subject areas

  • Medicine(all)

Fields of Expertise

  • Human- & Biotechnology

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