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

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. Common 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.

Light Stimulation of Neurons on Organic Photocapacitors Induces Action Potentials with Millisecond Precision

“…The parameters were derived from experiments performed in TagRFP‐K v 1.3 transfected HEK293 cells to model the activation and deactivation, respectively (Figure S2A–C, Supporting Information) using particle swarm optimization with a hybrid function (particleswarm MATLAB Mathworks, global optimization toolbox, swarm size, 200, hybrid function fmincon). [ 28 ] The model bounds were based on the description of Kv1.3 in ref. [26] and set to lower bound = [100, 0.01, 90, 0.1, 2000, 1500, 8000], upper bound = [500, 0.5200, 1, 50 000, 9000, 20 000] for the set of parameters , respectively.…”

Shedding Light on Cardiac Excitation: In Vitro and In Silico Analysis of Native Ca2+ Channel Activation in Guinea Pig Cardiomyocytes Using Organic Photovoltaic Devices

“…where O is the fraction of open channels [35], which depends on voltage, time, and Ca 2+ -concentration in the subspace compartment [Ca 2+ ]d and 𝑃 ̅ Ca is the maximal permeability of the channel for Ca 2+ ions, scaling the amplitude of the current [36]. 𝛿 represents the driving term accounting for the electrochemical forces driving the ionic movement defined by the Goldman-Hodgkin-Katz (GHK) flux equation ( 4)…”

Application of Spectral Methods of Analysis for Description of Ultradian Biorhythms at the Levels of Physiological Systems, Cells and Molecules (Review)

“…General approaches describe either the Hodgkin-Huxley model (HH) or the hidden Markov model (HMM) [371][372][373], depending on the level of detail of the functional and structural changes in the main channel gating and taking into account the computational effort to develop the model. In addition, attempts are being made to model the behavior of ion channels using systems theory [374].…”