Hypoxic Stress-Dependent Regulation of Na,K-ATPase in Ischemic Heart Disease

In cardiomyocytes, regular activity of the Na,K-ATPase (NKA) and its Na/K pump activity is essential for maintaining ion gradients, excitability, propagation of action potentials, electro-mechanical coupling, trans-membrane Na+ and Ca2+ gradients and, thus, contractility. The activity of NKA is impaired in ischemic heart disease and heart failure, which has been attributed to decreased expression of the NKA subunits. Decreased NKA activity leads to intracellular Na+ and Ca2+ overload, diastolic dysfunction and arrhythmias. One signal likely related to these events is hypoxia, where hypoxia-inducible factors (HIF) play a critical role in the adaptation of cells to low oxygen tension. HIF activity increases in ischemic heart, hypertension, heart failure and cardiac fibrosis; thus, it might contribute to the impaired function of NKA. This review will mainly focus on the regulation of NKA in ischemic heart disease in the context of stressed myocardium and the hypoxia-HIF axis and argue on possible consequences of treatment.

Automated summary

In cardiomyocytes, the activity of Na,K-ATPase (NKA) and its Na/K pump is essential for maintaining ion gradients, excitability, and contractility. Impaired NKA activity in ischemic heart disease and heart failure, attributed to decreased expression of NKA subunits, leads to intracellular ion overload and dysfunction. Hypoxia-inducible factors (HIF) likely play a role in this impairment, as their activity increases in ischemic heart and cardiac pathologies. This review focuses on the regulation of NKA in ischemic heart disease and the potential consequences of treatment.