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Figure 5 Modeled Reduction in Calcium Uptake

Modeled reduction in calcium uptake >70% (but not altered transient outward current [I_to] or sodium channel inactivation) causes AP and TWA at 109 beats/min. (A) Human left ventricle (LV) wedge dimensions (endocardium = orange; mid-myocardium = light green; epicardium = light blue). (B) Spectral AP alternans and TWA develop in the endocardium as sarcoplasmic reticulum calcium uptake current [I_up] reduces to 0.25 to 0.30 of baseline. (C) Mean change in endocardial phase II amplitude (middle left panel) and peak diastolic intracellular calcium ([Ca]i) (far right panel) computed at locations indicated by gray circles (far left and middle right panels). The number of alternating beats out of 64 is indicated. (D, top) Control endocardial AP and pseudo-electrocardiogram with bounding boxes, denoted by dashed lines, depicting AP phase II and T-wave data ranges. (D, bottom) AP phase II and T-wave alternans for I_up reduced by 74%; red lines = odd; blue lines = even; orange lines = control. Note similarity to clinical alternans (Figs. 1, 2, and 3B). T-wave locations used to compute TWA amplitude differences are denoted by *. Abbreviations as in Figure 1.