The Relationship Between P38–MAPK and AMPK During Myocardial Ischaemia

p38 mitogen-activated protein kinase (p38–MAPK) and AMP-activated protein kinase (AMPK) are activated by, and influence sensitivity to, myocardial ischaemia. Recently a number of studies have suggested that AMPK may participate in the activation of p38–MAPK. We therefore examined whether AMPK may be the principal “ischaemia sensor” responsible for p38–MAPK activation during myocardial ischaemia. The activities of AMPK and p38–MAPK were temporally related in adult rat ventricular myocytes (ARVM) subjected to simulated ischemia and in isolated mouse hearts subjected to no-flow ischemia. However p38–MAPK activation was unaltered in mouse hearts lacking the predominant myocardial isoform, AMPKα2. Whilst in ARVM, adenoviral-driven expression of the minor myocardial isoform AMPKα1, in a constitutively active or dominant negative form expected also to reduce AMPKα2 activity, did not alter p38–MAPK activation under basal conditions or during simulated ischaemia.