Activation of AMP-activated Protein Kinase Stimulates Na+,K+-ATPase Activity in Skeletal Muscle Cells

Abstract

Background: Contractions activate the sodium pump, Na ϩ ,K ϩ -ATPase, and the energy sensor, AMP-activated protein

Activation of AMP-activated Protein Kinase Regulates Hippocampal Neuronal pH by Recruiting Na+/H+ Exchanger NHE5 to the Cell Surface

“…Moreover, mutations that block phosphorylation of the proximal AMPK recognition site prevented the AA-induced increase in NHE5 surface expression and activity. These findings complement earlier observations that AMPK can regulate membrane trafficking and surface levels of other solute carriers linked to energy and electrolyte homeostasis, including glucose transporters GLUT3 (60) and GLUT4 (61) and the Na ϩ /K ϩ -ATPase pump (62). Moreover, this interaction was relatively specific to the NHE5 isoform in so far as AMPK␣1 or AMPK␣2 oligomers did not form a complex with NHE1 and acute AICAR activation of AMPK did not regulate NHE1 activity in heterologous cell systems.…”

Energy-sensitive regulation of Na+/K+-ATPase by Janus kinase 2

“…Whereas acute hypoxia alters only the membrane abundance of the Na ϩ /K ϩ -ATPase (21), long-term hypoxia leads to decreased total Na ϩ /K ϩ -ATPase levels (20). On the other hand, AMPK has been reported to upregulate Na ϩ /K ϩ -ATPase activity (4,9), the opposite of what is seen following expression of JAK2. The AMPKinduced downregulation of Na ϩ /K ϩ -ATPase surface abundance was attributed to AS160, a Rab-GTPase-activating protein fostering internalization of the pump (4).…”

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

“…In active skeletal muscle, however, AMPK is activated in parallel to Na + /K + ATPase and contributes to the upregulation of the pump under this condition. 130 It should be kept in mind that excitable cells would presumably not decrease energy consumption following depolarization (see above). Moreover, inhibition of Na + /K + ATPase would be expected to increase the cytosolic Na + concentration, which could, at least in theory, reverse the Na + /Ca 2+ exchanger action thus resulting in Ca 2+ uptake with subsequent energy-consuming muscle contraction.…”