Modeling CaMKII in cardiac physiology: from molecule to tissue

Post-translational modification of membrane proteins (e.g., ion channels, receptors) by protein kinases is an essential mechanism for control of excitable cell function. Importantly, loss of temporal and/or spatial control of ion channel post-translational modification is common in congenital and ac...

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Main Authors:	Onal, Birce, Unudurthi, Sathya D., Hund, Thomas J.
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912431/

id	pubmed-3912431
recordtype	oai_dc
spelling	pubmed-39124312014-02-18 Modeling CaMKII in cardiac physiology: from molecule to tissue Onal, Birce Unudurthi, Sathya D. Hund, Thomas J. Pharmacology Post-translational modification of membrane proteins (e.g., ion channels, receptors) by protein kinases is an essential mechanism for control of excitable cell function. Importantly, loss of temporal and/or spatial control of ion channel post-translational modification is common in congenital and acquired forms of cardiac disease and arrhythmia. The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates a number of diverse cellular functions in heart, including excitation-contraction coupling, gene transcription, and apoptosis. Dysregulation of CaMKII signaling has been implicated in human and animal models of disease. Understanding of CaMKII function has been advanced by mathematical modeling approaches well-suited to the study of complex biological systems. Early kinetic models of CaMKII function in the brain characterized this holoenzyme as a bistable molecular switch capable of storing information over a long period of time. Models of CaMKII activity have been incorporated into models of the cell and tissue (particularly in the heart) to predict the role of CaMKII in regulating organ function. Disease models that incorporate CaMKII overexpression clearly demonstrate a link between its excessive activity and arrhythmias associated with congenital and acquired heart disease. This review aims at discussing systems biology approaches that have been applied to analyze CaMKII signaling from the single molecule to intact cardiac tissue. In particular, efforts to use computational biology to provide new insight into cardiac disease mechanisms are emphasized. Frontiers Media S.A. 2014-02-04 /pmc/articles/PMC3912431/ /pubmed/24550832 http://dx.doi.org/10.3389/fphar.2014.00009 Text en Copyright © 2014 Onal, Unudurthi and Hund. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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	Onal, Birce Unudurthi, Sathya D. Hund, Thomas J.
spellingShingle	Onal, Birce Unudurthi, Sathya D. Hund, Thomas J. Modeling CaMKII in cardiac physiology: from molecule to tissue
author_facet	Onal, Birce Unudurthi, Sathya D. Hund, Thomas J.
author_sort	Onal, Birce
title	Modeling CaMKII in cardiac physiology: from molecule to tissue
title_short	Modeling CaMKII in cardiac physiology: from molecule to tissue
title_full	Modeling CaMKII in cardiac physiology: from molecule to tissue
title_fullStr	Modeling CaMKII in cardiac physiology: from molecule to tissue
title_full_unstemmed	Modeling CaMKII in cardiac physiology: from molecule to tissue
title_sort	modeling camkii in cardiac physiology: from molecule to tissue
description	Post-translational modification of membrane proteins (e.g., ion channels, receptors) by protein kinases is an essential mechanism for control of excitable cell function. Importantly, loss of temporal and/or spatial control of ion channel post-translational modification is common in congenital and acquired forms of cardiac disease and arrhythmia. The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates a number of diverse cellular functions in heart, including excitation-contraction coupling, gene transcription, and apoptosis. Dysregulation of CaMKII signaling has been implicated in human and animal models of disease. Understanding of CaMKII function has been advanced by mathematical modeling approaches well-suited to the study of complex biological systems. Early kinetic models of CaMKII function in the brain characterized this holoenzyme as a bistable molecular switch capable of storing information over a long period of time. Models of CaMKII activity have been incorporated into models of the cell and tissue (particularly in the heart) to predict the role of CaMKII in regulating organ function. Disease models that incorporate CaMKII overexpression clearly demonstrate a link between its excessive activity and arrhythmias associated with congenital and acquired heart disease. This review aims at discussing systems biology approaches that have been applied to analyze CaMKII signaling from the single molecule to intact cardiac tissue. In particular, efforts to use computational biology to provide new insight into cardiac disease mechanisms are emphasized.
publisher	Frontiers Media S.A.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912431/
_version_	1612054266042646528

Modeling CaMKII in cardiac physiology: from molecule to tissue

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