Collectively, these data support a context-dependent, multi-node framework with predominantly atrial-directed effects: in post-MI atria, an Adam19–TGF-β/Smad2/3 node plausibly mediates anti-remodelling benefits, whereas in ACh/CaCl2 the benefit may reflect mitigation of IK, ACh-associated AERP shortening and improved Ca2+ handling. Here, SMAD2 is linked to myocardial infarction.