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Stability and sustained oscillations in a ventricular cardiomyocyte model.

Bogdan Amuzescu, Adelina Georgescu, Gheorghe Nistor, Marin Popescu, Istvan Svab, Maria Luiza Flonta, Alexandru Dan Corlan,

Interdiscip Sci. 4(1):1-18, 2012

ABSTRACT

The Luo-Rudy I model, describing the electrophysiology of a ventricular cardiomyocyte, is associated with an 8-dimensional discontinuous dynamical system with logarithmic and exponential non-linearities depending on 15 parameters. The associated stationary problem was reduced to a nonlinear system in only two unknowns, the transmembrane potential V and the intracellular calcium concentration [Ca]( i ). By numerical approaches appropriate to bifurcation problems, sections in the static bifurcation diagram were determined. For a variable steady depolarizing or hyperpolarizing current (I (st)), the corresponding projection of the static bifurcation diagram in the (I (st), V) plane is complex, featuring three branches of stationary solutions joined by two limit points. On the upper branch oscillations can occur, being either damped at a stable focus or diverted to the lower branch of stable stationary solutions when reaching the unstable manifold of a homoclinic saddle, thus resulting in early after-depolarizations (EADs). The middle branch of solutions is a series of unstable saddle points, while the lower one a series of stable nodes. For variable slow inward and K(+) current maximal conductances (g (si) and g (K)), in a range between 0 and 4-fold normal values, the dynamics is even more complex, and in certain instances sustained oscillations tending to a limit cycle appear. All these types of behavior were correctly predicted by linear stability analysis and bifurcation theory methods, leading to identification of Hopf bifurcation points, limit points of cycles and period doubling bifurcations. In particular settings, e.g. one-fifth-of-normal g (si), EADs and sustained high amplitude oscillations due to an unstable resting state may occur simultaneously.

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