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- W159743246 abstract "Intracellular Ca2+ dynamics of cardiac myocytes are regulated by complexmechanisms of a variety of ion channels, transporters, and exchangers. Alterations of these Ca2+regulatory components might lead to development of cardiac diseases. To investigate the regulatory mechanismsand hidden Ca2+ dynamics we use integrative systems analysis. Herein, we brieflysummarize cardiac systems biology and, within the context of cardiac systems biology, identify the functionalrole of key Ca2+ regulatory proteins and their influence on intracellular Ca2+dynamics (i.e., Ca2+ transient, SR Ca2+ content, CICRgain, half-decay time) using parameter sensitivity analysis based on an experimentally validated mathematicalmodel of mouse ventricular myocytes. In addition, we analyze the influence of the pacing period (frequency)of a stimulus current since most of the Ca2+ regulatory proteins react withdifferent timescales. Throughout the parameter sensitivity analysis, we found that alteration of SERCAor LTCC has a more significant effect on the Ca2+ dynamics than that ofRyR or NCX. In particular, for the 70% down-regulation of LTCC, the Ca2+ influxthrough LTCC failed to initialize the SR Ca2+ release and thereby the intracellularCa2+ dynamics was dramatically changed. We also found that the pacing periodhas a significant effect on the half-decay time of the Ca2+ transients.These findings provide us with new insights into the pathophysiology of cardiac failure as well as the developmentof new therapeutic strategies." @default.
- W159743246 created "2016-06-24" @default.
- W159743246 creator A5058517260 @default.
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- W159743246 creator A5079201651 @default.
- W159743246 creator A5080294115 @default.
- W159743246 date "2008-01-01" @default.
- W159743246 modified "2023-09-25" @default.
- W159743246 title "Cardiac Systems Biology and Parameter Sensitivity Analysis: Intracellular Ca2+ Regulatory Mechanisms in Mouse Ventricular Myocytes" @default.
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- W159743246 doi "https://doi.org/10.1007/10_2007_093" @default.
- W159743246 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18437298" @default.
- W159743246 hasPublicationYear "2008" @default.
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