Abstract
The dynamical mechanisms of early afterdepolarizations (EADs) were investigated by bifurcation analyses, as well as numerical simulations, using a mathematical model of human ventricular myocytes. On the basis of experimental data, we have developed a human ventricular model as a modified version of previous models. The stability of equilibrium points (EPs), bifurcation structures, and oscillation dynamics of the model system was determined as functions of the L-type Ca2+ channel conductance (gCa,L), delayed-rectifier K+ channel conductance (gKr, gKs), or noninactivating sodium channel conductance (gNass). We first examined how EADs appear in the normal system and in long QT syndromes, which were simulated by decreasing gKs (LQT1), decreasing gKr (LQT2), or increasing gNass (LQT3). EADs appeared in the vicinity of Hopf bifurcation (HB) points, when gCa,L was increased, or when gKs and/or gKr was decreased. The threshold (critical gCa,L value) for EADs to appear during gCa,L increases was much lower in the LQTs than in the normal system; the critical gK was much higher in the LQTs. We further identified the gating variable of the slowly-activating delayed-rectifier K+ current (n) as a slow subsystem, exploring the effects of a parameter n (gKs) on the bifurcation structures of the fast subsystem (slow-fast decomposition analysis). Facilitation of the EAD generation in the LQTs appeared to be due to the shift in HB values toward higher n (gKs) values. [Jpn J Physiol 54 Suppl:S104 (2004)]
