A Global Sensitivity Tool for Cardiac Cell Modeling: Application to Ionic Current Balance and Hypertrophic Signaling

Sher, Anna A., Cooling, Michael T., Bethwaite, Blair, Tan, Jefferson, Peachey, Tom, Enticott, Colin, Garic, Slavisa, Gavaghan, David J., Noble, Denis, Abramson, David and Crampin, Edmund J. (2010). A Global Sensitivity Tool for Cardiac Cell Modeling: Application to Ionic Current Balance and Hypertrophic Signaling. In: Proceedings of the 32nd Annual international conference of the IEEE engineering in medicine and biology society. 32nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 10), Buenos Aires, Argentina, (1498-1502). 31 August-04 September 2010. doi:10.1109/IEMBS.2010.5626841


Author Sher, Anna A.
Cooling, Michael T.
Bethwaite, Blair
Tan, Jefferson
Peachey, Tom
Enticott, Colin
Garic, Slavisa
Gavaghan, David J.
Noble, Denis
Abramson, David
Crampin, Edmund J.
Title of paper A Global Sensitivity Tool for Cardiac Cell Modeling: Application to Ionic Current Balance and Hypertrophic Signaling
Conference name 32nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 10)
Conference location Buenos Aires, Argentina
Conference dates 31 August-04 September 2010
Proceedings title Proceedings of the 32nd Annual international conference of the IEEE engineering in medicine and biology society   Check publisher's open access policy
Journal name IEEE Engineering in Medicine and Biology Society. Conference Proceedings   Check publisher's open access policy
Place of Publication Piscataway, NJ United States
Publisher I E E E
Publication Year 2010
Year available 2010
Sub-type Fully published paper
DOI 10.1109/IEMBS.2010.5626841
Open Access Status Not Open Access
ISBN 9781424441242
1424441242
ISSN 1557-170X
Start page 1498
End page 1502
Total pages 5
Language eng
Formatted Abstract/Summary
Cardiovascular diseases are the major cause of death in the developed countries. Identifying key cellular processes involved in generation of the electrical signal and in regulation of signal transduction pathways is essential for unraveling the underlying mechanisms of heart rhythm behavior. Computational cardiac models provide important insights into cardiovascular function and disease. Sensitivity analysis presents a key tool for exploring the large parameter space of such models, in order to determine the key factors determining and controlling the underlying physiological processes. We developed a new global sensitivity analysis tool which implements the Morris method, a global sensitivity screening algorithm, onto a Nimrod platform, which is a distributed resources software toolkit. The newly developed tool has been validated using the model of IP3-calcineurin signal transduction pathway model which has 30 parameters. The key driving factors of the IP3 transient behaviour have been calculated and confirmed to agree with previously published data. We next demonstrated the use of this method as an assessment tool for characterizing the structure of cardiac ionic models. In three latest human ventricular myocyte models, we examined the contribution of transmembrane currents to the shape of the electrical signal (i.e. on the action potential duration). The resulting profiles of the ionic current balance demonstrated the highly nonlinear nature of cardiac ionic models and identified key players in different models. Such profiling suggests new avenues for development of methodologies to predict drug action effects in cardiac cells.
Q-Index Code E1
Q-Index Status Provisional Code
Institutional Status Non-UQ

 
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