Figure 5.

Effects of “Boosted” Mex Cellular Dynamics

(A) Overlay of APs and DIII-VSD fluorescence in the absence (black) and presence (red) of Mex 10 μM for WT (left), R1626P (middle), and M1652R (right). In response to voltage depolarization (the AP), the DIII-VSD (dashed lines) fluoresces before decaying to its resting value at –80 mV (∼93% for WT). For R1626P, the DIII-VSD remains 100% activated throughout the duration of the AP. In M1652 (far right), the DIII-VSD relaxes to ∼75%, activated both in the presence and absence of Mex. Application of “boosted” Mex “holds up” the DIII-VSD to ∼90% (dashed blue trace). (B) The effects of “boosted” Mex (Mex 10 μM + “booster”) on APs. “Boosted” Mex (shown in blue) abolishes EAD triggers, failed repolarization, and normalizes the AP toward WT (gray trace). (C) Late Na⁺ current is dramatically decreased, with a monotonic decrease back to baseline after each AP, similar to WT. (D) APD as a function of cycle number for 100 beats at BCL2000 corresponding to the APs shown in B. Note that with “boosted Mex” (blue dots), there is normalization of APD similar to WT. Abbreviations as in Figures 1 and 3.