Graphical Abstract.
A novel integrative human atrial electrophysiology and signalling model reveals synergistic PKA and CaMKII interactions promoting delayed after depolarizations and triggered action potentials in both atrial myocytes and tissues. CaMKII, Ca2+/CaM-dependent protein kinase II; Cx, connexin; IK1, inward rectifier K+ current; INa, fast Na+ current; ICaL, L-type Ca2+ current; NCX, Na+/Ca2+ exchanger; NKA, Na+/K+ ATPase; PLB, phospholamban; PLM, phospholemman; RyR, ryanodine receptor 2; SERCA, sarco/endoplasmic reticulum Ca2+ ATPase; βAR, β adrenergic receptor; PKA, protein kinase A.