Epac in cardiac calcium signaling

► Epac is an exchange protein directly activated by cAMP. ► Epac increases Ca2 + spark rate and intranuclear Ca2 + in ventricular cardiac myocytes. ► PLC, PKC, CaMKII, IP3, and calcineurin are involved in Epac actions. ► Epac induces HDAC5 translocation, MEF2 activation and calmodulin upregulation. ► Epac affects excitation-contraction and excitation-transcription coupling.