Protein kinase C (PKC) activation is classically considered as independent of the β-adrenergic pathway. However, the cAMP-activated exchange factor Epac was recently shown to activate phospholipase C. β-A stimulation is thus likely to stimulate PKC. We evaluated in cardiomyocytes whether βA stimulation could activate PKC. Rat neonatal cardiomyocytes were subjected to isoproterenol stimulation (ISO). Inositol trisphosphate production was increased by 50 % by 1μm ISO (p<0.05) and PKC was translocated to particulate fractions (western blot) in the perinuclear area (confocal microscopy) in a PKA-independent manner since it was not inhibited by an infection with an adenovirus encoding a protein kinase A (PKA) inhibitor. Instead, PKC activation was Epac dependent since 8-CPT, an Epac activator, induced the same PKC translocation as ISO and siRNAs of Epac completetly inhibited PKC activation. The same translocation of PKC in PF induced by βA stimulation was found in adult isolated rat hearts perfused by ISO with a sarcolemmmal membrane localization. This was associated with a phosphorylation of connexin-43 on ser368 that was blocked by the PKC inhibitor BIM. In conclusion, these data demonstrate a new interconnection between β-adrenergic and PKC pathways via Epac in cardiac cells with a potential role in cell-to-cell communications.Le texte complet de cet article est disponible en PDF.