The Na⁺/K⁺ pumps are members of the P-type family of active cation transport proteins. They consume ATP to actively transport Na⁺ out of and K⁺ into the cell. Na⁺ and K⁺ gradients are required for maintaining membrane potential, cell volume and secondary transport of other solutes thus making these pumps essential for all mammalian cells.
 
The minimum functional unit of the Na⁺/K⁺ pump consists of a heterodimer of α- and β- subunits¹. The α subunit (also known as ATP1A) has a molecular mass of about 100 kDa and four distinct isoforms have been identified so far. It has ten transmembrane segments, short extracellular loops and larger cytoplasmic regions. There is a large central loop between M4 and M5 composed of 430 amino acid residues and a long N-terminal tail of about 90 amino acid residues. The nucleotide-binding domain (N domain) and phosphorylation domain (P domain) of the pump are formed by the M4/M5 loop while the actuator domain (A domain) is formed by the amino-terminal tail and the M2/M3 loop. The major isoform, α1, is found in most tissues and is the major form in the kidney and in most epithelia cells. The β-subunit is essential for the delivery and insertion of the α-subunit into the cell’s membrane, whilst β-subunit delivery to the membrane is not dependent on α-subunit expression².
 
ATP1A2 mutations that cause diverse functional abnormalities of the Na⁺/K⁺ pump have been implicated in the pathogenesis of familial hemiplegic migraine³.