Regulation of the Cardiac Na+/K+-ATPase by Phospholemman

Phospholemman (PLM) is a regulatory subunit of the cardiac Na+/K+-ATPase (NKA), but exists also as an independent tetramer. The membrane-spanning protein consists of 72-amino acid residues and is the first member of the FXYD motif-containing family of tissue-specific NKA regulatory subunits (FXYD1). A comparative model of the human PLM/NKA complex shows the interactions between NKA and the extracellular FXYD motif as well as the transmembrane helix-helix interactions. A variety of intracellular posttranslational modifications point to a highly dynamic picture of interactions between NKA and the intracellular part of PLM. Posttranslational modifications of PLM include NKA-activating phosphorylation, inhibiting palmitoylation and activating glutathionylation. PLM gene expression has the potential for posttranscriptional regulation by the formation of potassium-ion-stabilised G-quadruplex structures in pre-splicing mRNA. The overall physiological role of cardiac PLM is to protect the heart under conditions of increased heart rate and oxidative stress avoiding calcium overload of the cytoplasm and arrhythmias. The PLM tetramer possibly exists as a storage pool in order for the heart to react quickly to changing conditions.