Determinants of Beat-to-Beat Variability of Repolarization Duration in the Canine Ventricular Myocyte: A Computational Analysis
Figure 9
Mechanisms underlying increased BVR under LQT1 conditions with SR Ca2+ overload.
A. STV vs. APD relationship under control (open symbols) or LQT1 conditions (filled symbols) in individual canine ventricular myocytes (left panel). Right panel shows the parameters of the non-linear fit of the STV vs. APD relationship under control or LQT1 conditions (solid and dashed lines in left panel, respectively), or under LQT2 conditions (from Figure 8). B. Consecutive APDs (top panel) and Ca2+-transient amplitudes (middle panel) during simulated application of 1.0 µmol/L isoproterenol (ISO) at a 500-ms CL in the deterministic model. Membrane potential and intracellular [Ca2+] for the beats indicated by the black vertical boxes are shown in the bottom panel. APD (in ms) is indicated below each beat and a Poincaré plot is shown on the right. Simulations were performed with 100% IKs inhibition to simulate LQT1 conditions and with 10% inhibition of INaK, resulting in increased [Na+]i and reduced Ca2+ extrusion via INaCa, to promote Ca2+-handling abnormalities. C. Similar to panel B for the stochastic model with a single domain. D. Similar to panel B for the stochastic model divided into four identical domains connected via Ca2+-diffusion terms with time constant τ = 20 ms.