Statistical Approach to Incorporating Experimental Variability into a Mathematical Model of the Voltage-Gated Na+ Channel and Human Atrial Action Potential
| Autor: | Seth H. Weinberg, Thomas J. Hund, Alexander J. Winkle, Daniel Gratz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Atrial action potential Computer science QH301-705.5 Action Potentials 030204 cardiovascular system & hematology arrhythmia Bayesian statistics Article NAV1.5 Voltage-Gated Sodium Channel 03 medical and health sciences 0302 clinical medicine voltage-gated sodium channel Humans Computer Simulation Myocytes Cardiac atrial fibrillation Biology (General) Mathematical model Sodium channel Cardiac myocyte Cardiac arrhythmia Cardiac action potential Bayes Theorem General Medicine Models Theoretical Atrial Function electrophysiology Electrophysiology computational model 030104 developmental biology cardiovascular system Biological system |
| Zdroj: | Cells, Vol 10, Iss 1516, p 1516 (2021) Cells Volume 10 Issue 6 |
| ISSN: | 2073-4409 |
| Popis: | The voltage-gated Na+ channel Nav1.5 is critical for normal cardiac myocyte excitability. Mathematical models have been widely used to study Nav1.5 function and link to a range of cardiac arrhythmias. There is growing appreciation for the importance of incorporating physiological heterogeneity observed even in a healthy population into mathematical models of the cardiac action potential. Here, we apply methods from Bayesian statistics to capture the variability in experimental measurements on human atrial Nav1.5 across experimental protocols and labs. This variability was used to define a physiological distribution for model parameters in a novel model formulation of Nav1.5, which was then incorporated into an existing human atrial action potential model. Model validation was performed by comparing the simulated distribution of action potential upstroke velocity measurements to experimental measurements from several different sources. Going forward, we hope to apply this approach to other major atrial ion channels to create a comprehensive model of the human atrial AP. We anticipate that such a model will be useful for understanding excitability at the population level, including variable drug response and penetrance of variants linked to inherited cardiac arrhythmia syndromes. |
| Databáze: | OpenAIRE |
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