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