Figure 7.

Effects of Mex on a 100-Cell 1D Cardiac Fiber

Note that for all panels, time is on the x axis, cell number is on the y axis (1→100), and voltage is in the z axis. Full details of the fiber simulation are in the Supplemental Material. The last 2 beats of a 50-beat simulation at BCL2000 are shown for each condition. (A) Schematic of a 1-dimensional (1D) cardiac fiber. Single ventricular myocytes were electrotonically “coupled together” by simulated gap junctions. The fiber was stimulated at cell 1, and currents and transmembrane voltage were recorded for each cell in the cardiac fiber. (B) In the absence of Mex (top), the R1626P mutation shows EADs that persist throughout fiber. Application of Mex 10 μM (bottom) normalizes the AP. (C) For the M1652R mutation in the absence of Mex, the 49th and 50th beats represent a failure of the repolarization regime, indicating sustained arrhythmia (top). Mex (10 μM) repolarizes the membrane, but sustained EADs are present throughout the fiber (bottom). (D) The WT drug-free model shows narrow APs that easily propagate throughout the fiber (top). When the M1652R mutation is treated with 10 μM of “boosted” Mex (bottom), the AP normalizes dramatically and resembles the WT phenotype. Abbreviations as in Figures 1 and 3.