A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases

Genetically modified mice are popular experimental models for studying the molecular bases and mechanisms of cardiac arrhythmia. A postgenome challenge is to classify the functional roles of genes in cardiac function. To unveil the functional role of various genetic isoforms of ion channels in gener...

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Main Authors:	Kharche, Sanjay, Yu, Jian, Lei, Ming, Zhang, Henggui
Format:	Online
Language:	English
Published:	American Physiological Society 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191499/

id	pubmed-3191499
recordtype	oai_dc
spelling	pubmed-31914992012-09-01 A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases Kharche, Sanjay Yu, Jian Lei, Ming Zhang, Henggui Cardiac Excitation and Contraction Genetically modified mice are popular experimental models for studying the molecular bases and mechanisms of cardiac arrhythmia. A postgenome challenge is to classify the functional roles of genes in cardiac function. To unveil the functional role of various genetic isoforms of ion channels in generating cardiac pacemaking action potentials (APs), a mathematical model for spontaneous APs of mouse sinoatrial node (SAN) cells was developed. The model takes into account the biophysical properties of membrane ionic currents and intracellular mechanisms contributing to spontaneous mouse SAN APs. The model was validated by its ability to reproduce the physiological exceptionally short APs and high pacing rates of mouse SAN cells. The functional roles of individual membrane currents were evaluated by blocking their coding channels. The roles of intracellular Ca2+-handling mechanisms on cardiac pacemaking were also investigated in the model. The robustness of model pacemaking behavior was evaluated by means of one- and two-parameter analyses in wide parameter value ranges. This model provides a predictive tool for cellular level outcomes of electrophysiological experiments. It forms the basis for future model development and further studies into complex pacemaking mechanisms as more quantitative experimental data become available. American Physiological Society 2011-09 2011-07-01 /pmc/articles/PMC3191499/ /pubmed/21724866 http://dx.doi.org/10.1152/ajpheart.00143.2010 Text en Copyright © 2011 the American Physiological Society This document may be redistributed and reused, subject to www.the-aps.org/publications/journals/funding_addendum_policy.htm (http://www.the-aps.org/publications/journals/funding_addendum_policy.htm) .
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kharche, Sanjay Yu, Jian Lei, Ming Zhang, Henggui
spellingShingle	Kharche, Sanjay Yu, Jian Lei, Ming Zhang, Henggui A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases
author_facet	Kharche, Sanjay Yu, Jian Lei, Ming Zhang, Henggui
author_sort	Kharche, Sanjay
title	A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases
title_short	A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases
title_full	A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases
title_fullStr	A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases
title_full_unstemmed	A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases
title_sort	mathematical model of action potentials of mouse sinoatrial node cells with molecular bases
description	Genetically modified mice are popular experimental models for studying the molecular bases and mechanisms of cardiac arrhythmia. A postgenome challenge is to classify the functional roles of genes in cardiac function. To unveil the functional role of various genetic isoforms of ion channels in generating cardiac pacemaking action potentials (APs), a mathematical model for spontaneous APs of mouse sinoatrial node (SAN) cells was developed. The model takes into account the biophysical properties of membrane ionic currents and intracellular mechanisms contributing to spontaneous mouse SAN APs. The model was validated by its ability to reproduce the physiological exceptionally short APs and high pacing rates of mouse SAN cells. The functional roles of individual membrane currents were evaluated by blocking their coding channels. The roles of intracellular Ca2+-handling mechanisms on cardiac pacemaking were also investigated in the model. The robustness of model pacemaking behavior was evaluated by means of one- and two-parameter analyses in wide parameter value ranges. This model provides a predictive tool for cellular level outcomes of electrophysiological experiments. It forms the basis for future model development and further studies into complex pacemaking mechanisms as more quantitative experimental data become available.
publisher	American Physiological Society
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191499/
_version_	1611480207996223488

A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases

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