Role of the α2-isoform of AMP-activated protein kinase in the metabolic response of the heart to no-flow ischemia

AMP-activated protein kinase (AMPK) is a major sensor and regulator of the energetic state of the cell. Little is known about the specific role of AMPK alpha(2), the major AMPK isoform in the heart, in response to global ischemia. We used AMPK alpha(2)-knockout (AMPK alpha(-/-)(2)) mice to evaluate the consequences of AMPK alpha(2) deletion during normoxia and ischemia, with glucose as the sole substrate. Hemodynamic measurements from echocardiography of hearts from AMPK alpha(-/-)(2) mice during normoxia showed no significant modification compared with wild-type animals. In contrast, the response of hearts from AMPK alpha(-/-)(2) mice to no-flow ischemia was characterized by a more rapid onset of ischemia-induced contracture. This ischemic contracture was associated with a decrease in ATP content, lactate production, glycogen content, and AMPK beta(2) content. Hearts from AMPK alpha(-/-)(2) mice were also characterized by a decreased phosphorylation state of acetyl-CoA carboxylase during normoxia and ischemia. Despite an apparent worse metabolic adaptation during ischemia, the absence of AMPK alpha(2) does not exacerbate impairment of the recovery of postischemic contractile function. In conclusion, AMPK alpha(2) is required for the metabolic response of the heart to no-flow ischemia. The remaining AMPK alpha(1) cannot compensate for the absence of AMPK alpha(2).