Regulation of ion channels and transporters by AMP-activated kinase (AMPK)

The energy-sensing AMP-activated kinase AMPK ensures survival of energy-depleted cells by stimulating ATP production and limiting ATP utilization. Both energy production and energy consumption are profoundly influenced by transport processes across the cell membane including channels, carriers and pumps. Accordingly, AMPK is a powerful regulator of transport across the cell membrane. AMPK regulates diverse K(+) channels, Na(+) channels, Ca(2+) release activated Ca(2+) channels, Cl(-) channels, gap junctional channels, glucose carriers, Na(+)/H(+)-exchanger, monocarboxylate-, phosphate-, creatine-, amino acid-, peptide- and osmolyte-transporters, Na(+)/Ca(2+)-exchanger, H(+)-ATPase and Na(+)/K(+)-ATPase. AMPK activates ubiquitin ligase Nedd4-2, which labels several plasma membrane proteins for degradation. AMPK further regulates transport proteins by inhibition of Rab GTPase activating protein (GAP) TBC1D1. It stimulates phosphatidylinositol 3-phosphate 5-kinase PIKfyve and inhibits phosphatase and tensin homolog (PTEN) via glycogen synthase kinase 3β (GSK3β). Moreover, it stabilizes F-actin as well as downregulates transcription factor NF-κB. All those cellular effects serve to regulate transport proteins.