Abstract
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 is 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.
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References
Cranefield, P.F., Aronson, R.S.: Cardiac arrhythmias: the role of triggered activity and other mechanisms. Futura Publishing Company (1988)
Fozzard, H.: Afterdepolarizations and triggered activity. Basic Res. Cardiol. 87(Suppl. 2), 105–113 (1992)
Hiraoka, M., Sunami, A., Zheng, F., Sawanobori, T.: Multiple ionic mechanisms of early afterdepolarizations in isolated ventricular myocytes from guinea-pig hearts. QT Prolongation and Ventricular Arrhythmias, pp. 33–34 (1992)
January, C., Moscucci, A.: Cellular mechanism of early afterdepolarizations. QT Prolongation and Ventricular Arrhythmias, pp. 23–32 (1992)
Zeng, J., Rudy, Y.: Early afterdepolarizations in cardiac myocytes: mechanism and rate dependence. Biophysical J. 68, 949–964 (1995)
Homma, N., Amran, M., Nagasawa, Y., Hashimoto, K.: Topics on the Na+/Ca2+ exchanger: involvement of Na+/Ca2+ exchange system in cardiac triggered activity. J. Pharmacol. Sci. 102, 17–21 (2006)
Clusin, W.: Calcium and cardiac arrhythmias: DADs, EADs, and alternans. Crit. Rev. Clin. Lab. Sci. 40, 337–375 (2003)
Charpentier, F., Drouin, E., Gauthier, C., Marec, H.L.: Early after/depolarizations and triggered activity: mechanisms and autonomic regulation. Fundam. Clin. Pharmacol. 7, 39–49 (1993)
Luo, C.H., Rudy, Y.: A dymanic model of the cardiac ventricular action potential: I. simulations of ionic currents and concentration changes. Circ. Res. 74, 1071–1096 (1994)
Hodgkin, A.L., Huxley, A.F.: A quantitative description of membrane currents and its application to conduction and excitation in nerve. J. Physiol. 117, 500–544 (1952)
Ye, P., Entcheva, E., Smolka, S., Grosu, R.: A cycle-linear hybrid-automata model for excitable cells. IET Systems Biology 2, 24–32 (2008)
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Ye, P., Grosu, R., Smolka, S.A., Entcheva, E. (2008). Formal Analysis of Abnormal Excitation in Cardiac Tissue. In: Heiner, M., Uhrmacher, A.M. (eds) Computational Methods in Systems Biology. CMSB 2008. Lecture Notes in Computer Science(), vol 5307. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-88562-7_13
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DOI: https://doi.org/10.1007/978-3-540-88562-7_13
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-88561-0
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