Action potential spike and dome and phase-2 reentry
It is well established that in large mammals, including humans and dogs, transient outward current (Ito) density is much greater in ventricular Epi vs. Endo cells and that this is responsible for a more pronounced spike and dome morphology of the AP in ventricular Epi than in Endo.16 Moreover, Epi of the RVOT is known to display a more pronounced spike and dome AP morphology than Epi of the rest of RV or LV.14,17The prominent AP notch in the RVOT Endo intra-trabecular structures is most likely due to the presence of a prominent Ito.
In previous studies, we and others have shown that a net outward shift in the balance of current during the early phases of AP can lead to accentuation of the AP notch, can result in loss of AP dome at some sites but not others in RV and LV Epi.13-15 This is observed following augmentation of Ito or IK-ATP (using NS5806 or pinacidil) or following inhibition of INa and/or ICa (using terfenadine, ajmaline or verapamil).13-15 When loss of the dome is spatially heterogeneous, it can lead to propagation of AP dome from regions in which it is maintained to regions where it is lost, resulting in a closely-coupled extrasystole due to phase 2 reentry.13,15