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
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 lev...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/2/239 |
| _version_ | 1797495226083835904 |
|---|---|
| author | Sonja Langthaler Jasmina Lozanović Šajić Theresa Rienmüller Seth H. Weinberg Christian Baumgartner |
| author_facet | Sonja Langthaler Jasmina Lozanović Šajić Theresa Rienmüller Seth H. Weinberg Christian Baumgartner |
| author_sort | Sonja Langthaler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T01:44:47Z |
| format | Article |
| id | doaj.art-fb0d4fbda991430e887015bbd2f04c95 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:44:47Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fb0d4fbda991430e887015bbd2f04c952023-11-23T13:18:17ZengMDPI AGCells2073-44092022-01-0111223910.3390/cells11020239Ion Channel Modeling beyond State of the Art: A Comparison with a System Theory-Based Model of the Shaker-Related Voltage-Gated Potassium Channel Kv1.1Sonja Langthaler0Jasmina Lozanović Šajić1Theresa Rienmüller2Seth H. Weinberg3Christian Baumgartner4Institute of Health Care Engineering with European Testing Center for Medical Devices, Graz University of Technology, A-8010 Graz, AustriaInstitute of Health Care Engineering with European Testing Center for Medical Devices, Graz University of Technology, A-8010 Graz, AustriaInstitute of Health Care Engineering with European Testing Center for Medical Devices, Graz University of Technology, A-8010 Graz, AustriaDepartment of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USAInstitute of Health Care Engineering with European Testing Center for Medical Devices, Graz University of Technology, A-8010 Graz, AustriaThe 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.https://www.mdpi.com/2073-4409/11/2/239ion channelselectrophysiologycomputational modelHodgkin–Huxleyhidden Markov modelsystem and control theory |
| spellingShingle | Sonja Langthaler Jasmina Lozanović Šajić Theresa Rienmüller Seth H. Weinberg Christian Baumgartner 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 Cells ion channels electrophysiology computational model Hodgkin–Huxley hidden Markov model system and control theory |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | ion channels electrophysiology computational model Hodgkin–Huxley hidden Markov model system and control theory |
| url | https://www.mdpi.com/2073-4409/11/2/239 |
| work_keys_str_mv | AT sonjalangthaler ionchannelmodelingbeyondstateoftheartacomparisonwithasystemtheorybasedmodeloftheshakerrelatedvoltagegatedpotassiumchannelkv11 AT jasminalozanovicsajic ionchannelmodelingbeyondstateoftheartacomparisonwithasystemtheorybasedmodeloftheshakerrelatedvoltagegatedpotassiumchannelkv11 AT theresarienmuller ionchannelmodelingbeyondstateoftheartacomparisonwithasystemtheorybasedmodeloftheshakerrelatedvoltagegatedpotassiumchannelkv11 AT sethhweinberg ionchannelmodelingbeyondstateoftheartacomparisonwithasystemtheorybasedmodeloftheshakerrelatedvoltagegatedpotassiumchannelkv11 AT christianbaumgartner ionchannelmodelingbeyondstateoftheartacomparisonwithasystemtheorybasedmodeloftheshakerrelatedvoltagegatedpotassiumchannelkv11 |