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Formal Analysis of Abnormal Excitation in Cardiac Tissue.*

P. Ye, R. Grosu, S.A. Smolka and E. Entcheva

We present the Piecewise Linear Approximation Model of Ion Channel contribution (PLAMIC) to cardiac excitation. We use the PLAMIC model to conduct formal analysis of cardiac arrhythmic events, namely Early Afterdepolarizations (EADs). The goal is to quantify (for the first time) the contribution of the overall sodium (Na+), potassium (K+) and calcium (Ca2+) currents to the occurrence of EADs during the plateau phase of the cardiac action potential (AP). Our analysis yields exact mathematical criteria for the separation of the parameter space for normal and EAD-producing APs, which was validated by simulations with classical AP models based on complex systems of nonlinear differential equations. Our approach offers a simple formal technique for the prediction of conditions leading to arrhythmias (EADs) from a limited set of experimental measurements, and can be invaluable for devising new anti-arrhythmic strategies.

In Proc. of CMSB'08, the 6th International Conference on Computational Methods in Systems Biology, Rostock, Germany, 2008, Springer, LNBI.

*This work was supported by the NSF Faculty Early Career Development Award CCR01-33583 and the NSF CCF05-23863 Award.