Dynamical analysis of the calcium signaling pathway in cardiac myocytes based on logarithmic sensitivity analysis

Abstract

Many cellular functions are regulated by the Ca2+ signal which contains specific information in the form of frequency, amplitude, and duration of the oscillatory dynamics. Any alterations or dysfunctions of components in the calcium signaling pathway of cardiac myocytes may lead to a diverse range of cardiac diseases including hypertrophy and heart failure. In this study, we have investigated the hidden dynamics of the intracellular Ca2+ signaling and the functional roles of its regulatory mechanism through in silico simulations and parameter sensitivity analysis based on an experimentally verified mathematical model. It was revealed that the Ca2+ dynamics of cardiac myocytes are determined by the balance among various system parameters. Moreover, it was found through the parameter sensitivity analysis that the self-oscillatory Ca2+ dynamics are most sensitive to the Ca2+ leakage rate of the sarcolemmal membrane and the maximum rate of NCX, suggesting that these two components have dominant effects on circulating the cytosolic Ca2+. ?? 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.