CARDIOVASCULAR PHYSIOLOGY Epac activation, altered calcium homeostasis and ventricular arrhythmogenesis in the murine heart

Abstract The recently described exchange protein directly activated by cAMP (Epac) has been implicated in distinct protein kinase A-independent cellular signalling pathways. We investigated the role of Epac activation in adrenergi-cally mediated ventricular arrhythmogenesis. In contrast to observations in control conditions (n=20), monophasic action potentials recorded in 2 of 10 intrinsically beating and 5 of 20 extrinsically paced Langendorff-perfused wild-type murine hearts perfused with the Epac activator 8-pCPT-2′-O-Me-cAMP (8-CPT, 1 μM) showed spontaneous triggered activity. Three of 20 such extrinsically paced hearts showed spontaneous ventricular tachycardia (VT). Programmed electrical stimulation provoked VT in 10 of 20 similarly treated hearts (P<0.001; n=20). However, there were no statistically significant accompanying changes (P&gt