IVA caused atrial arrhythmias in hearts and DADs in LAMs
Atrial arrhythmias, specifically AF, was not observed and were induced by programmed stimulations in the presence of IVA in 6 of 23 hearts (26.1%, p<0.05 vs. baseline) and 10 of 13 hearts (76.9%, p<0.05 vs. baseline) in hearts paced at a basal CLs of 350 and 570 ms, respectively (Fig 4B). In contrast, in hearts paced at 350ms and pretreated with either 2 nM ATX-II or 0.3 μM ACh, IVA (0.03-10 μM) significantly increased the incidence of atrial arrhythmias in 8 of 18 (44.4%,p<0.05 vs. ATX-II alone) or 13 of 21 (61.9%,p<0.05 vs. ACh alone) hearts, respectively (Fig 4C). The atrial single-cell patch-clamp tests indicated that IVA (0.1-3 μM) induced DADs but not EADs with incidences of 41.7% (5/12), 62.5% (5/8) and 50.0% (4/8) in control, ATX-II- and ACh-treated cells, respectively (compared to baseline, p<0.05 , Fig 5A-B).