Differential effects of AMP-activated protein kinase in isolated rat atria subjected to simulated ischemia–reperfusion depending on the energetic substrates available

MESTRE CORDERO, VICTORIA EVANGELINA; VÉLEZ, DÉBORA ELISABET; VARELA, ALICIA; HERMANN, ROMINA; REZNIK, FEDERICO JOAQUÍN; MARINA PRENDES, MARÍA GABRIELA; FERNÁNDEZ PAZOS, MARÍA DE LAS MERCEDES; SAVINO, ENRIQUE ALBERTO

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY

SPRINGER

Año: 2017 vol. 470 p. 367 - 383

0031-6768

AMP-activated protein kinase (AMPK) is a serine?threonine kinase that functions primarily as a metabolic sensorto coordinate anabolic and catabolic processes in the cell, viaphosphorylation of multiple proteins involved in metabolicpathways, aimed to re-establish energy homeostasis at a cellautonomouslevel. Myocardial ischemia and reperfusion representsa metabolic stress situation for myocytes. WhetherAMPK plays a critical role in the metabolic and functionalresponses involved in these conditions remains uncertain. Inthis study, in order to gain a deeper insight into the role ofendogenous AMPK activation during myocardial ischemiaand reperfusion, we explored the effects of the pharmacologicalinhibition ofAMPK on contractile function rat, contractilereserve, tissue lactate production, tissue ATP content, and cellularviability. For this aim, isolated atria subjected to simulated75 min ischemia?75 min reperfusion (Is-Rs) in the presenceor absence of the pharmacological inhibitor of AMPK(compound C) were used. Since in most clinical situations ofischemia?reperfusion the heart is exposed to high levels offatty acids, the influence of palmitate present in the incubationmedium was also investigated. The present results suggest thatAMPK activity significantly increases during Is, remainingactivated during Rs. The results support that intrinsic activationof AMPK has functional protective effects in the reperfusedatria when glucose is the only available energetic substratewhereas it is deleterious when palmitate is alsoavailable. Cellular viability was not affected by either of theseconditions.