Testing the limits of cardiac electrophysiology models through systematic variation of current

Mathematical models of the electrical response of cardiac cells are used to help develop an understanding of the electrophysiological properties of cardiac cells. Increasingly complex models are being developed in an effort to enhance the biological fidelity of the models and potentially increase th...

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Main Authors: Binaya Tuladhar, Hana M. Dobrovolny
Format: Article
Language:English
Published: AIMS Press 2020-01-01
Series:AIMS Mathematics
Subjects:
Online Access:https://www.aimspress.com/article/10.3934/math.2020009/fulltext.html
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author Binaya Tuladhar
Hana M. Dobrovolny
author_facet Binaya Tuladhar
Hana M. Dobrovolny
author_sort Binaya Tuladhar
collection DOAJ
description Mathematical models of the electrical response of cardiac cells are used to help develop an understanding of the electrophysiological properties of cardiac cells. Increasingly complex models are being developed in an effort to enhance the biological fidelity of the models and potentially increase their ability to predict electrical dynamics observed in vivo and in vitro. However, as the models increase in size, they have a tendency to become unstable and are highly sensitive to changes in established parameters. This means that such models might be unable to accurately predict person-to-person variability, dynamical changes due to disease pathologies that alter ionic currents, or the effect of treatment with antiarrhythmics. In this paper, we test the predictive limits of two mathematical models by altering the conductance of Ca<sup>2+</sup>, Na<sup>+</sup>, and K<sup>+</sup> channels. We assess changes in action potential duration (APD), rate dependence, hysteresis, dynamical behavior, and restitution as conductance is varied. We find model predictions of abrupt changes in measured quantities and differences in the predictions of the two models that might be missed in a less systematic approach. These features can be compared to experimental observations to help assess the fidelity of the models.
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spelling doaj.art-a097f55c6a4542859a0a843c5821119f2022-12-22T03:05:54ZengAIMS PressAIMS Mathematics2473-69882020-01-015114015710.3934/math.2020009Testing the limits of cardiac electrophysiology models through systematic variation of currentBinaya Tuladhar0Hana M. Dobrovolny1Department of Physics & Astronomy, Texas Christian University, Fort Worth, TX, USADepartment of Physics & Astronomy, Texas Christian University, Fort Worth, TX, USAMathematical models of the electrical response of cardiac cells are used to help develop an understanding of the electrophysiological properties of cardiac cells. Increasingly complex models are being developed in an effort to enhance the biological fidelity of the models and potentially increase their ability to predict electrical dynamics observed in vivo and in vitro. However, as the models increase in size, they have a tendency to become unstable and are highly sensitive to changes in established parameters. This means that such models might be unable to accurately predict person-to-person variability, dynamical changes due to disease pathologies that alter ionic currents, or the effect of treatment with antiarrhythmics. In this paper, we test the predictive limits of two mathematical models by altering the conductance of Ca<sup>2+</sup>, Na<sup>+</sup>, and K<sup>+</sup> channels. We assess changes in action potential duration (APD), rate dependence, hysteresis, dynamical behavior, and restitution as conductance is varied. We find model predictions of abrupt changes in measured quantities and differences in the predictions of the two models that might be missed in a less systematic approach. These features can be compared to experimental observations to help assess the fidelity of the models.https://www.aimspress.com/article/10.3934/math.2020009/fulltext.htmlmathematical modelingcardiac electrophysiologyaction potential durationionic currentsparameters
spellingShingle Binaya Tuladhar
Hana M. Dobrovolny
Testing the limits of cardiac electrophysiology models through systematic variation of current
AIMS Mathematics
mathematical modeling
cardiac electrophysiology
action potential duration
ionic currents
parameters
title Testing the limits of cardiac electrophysiology models through systematic variation of current
title_full Testing the limits of cardiac electrophysiology models through systematic variation of current
title_fullStr Testing the limits of cardiac electrophysiology models through systematic variation of current
title_full_unstemmed Testing the limits of cardiac electrophysiology models through systematic variation of current
title_short Testing the limits of cardiac electrophysiology models through systematic variation of current
title_sort testing the limits of cardiac electrophysiology models through systematic variation of current
topic mathematical modeling
cardiac electrophysiology
action potential duration
ionic currents
parameters
url https://www.aimspress.com/article/10.3934/math.2020009/fulltext.html
work_keys_str_mv AT binayatuladhar testingthelimitsofcardiacelectrophysiologymodelsthroughsystematicvariationofcurrent
AT hanamdobrovolny testingthelimitsofcardiacelectrophysiologymodelsthroughsystematicvariationofcurrent