Sodium-potassium adenosine tri-phosphatase (Na+ /K+ ATPase)
is an enzyme that present in the plasma membrane of all mammalian cells and
works to pump Na+ out and K+ in against their concentration gradients,
obtaining the required energy through the hydrolysis of ATP [1]. The
transmembrane protein complex is composed of an α and a β subunit. The α
subunit is the channel with ATPase activity, while β subunit has a regulatory
function. Naturally occurring isoforms for every subunit include α1 & α2
and β1 & β2.
While in action, the pump binds an ATP molecule and 3
intracellular Na+ ions. As the ATP is hydrolyzed, phosphorylation of the pump
at a highly conserved aspartate residue occurs and subsequently ADP is
released. This is followed by a conformational change that exposes the Na+ ions
to the cellular outside. As the phosphorylated form of the pump has a low
affinity for Na+ ions, this allows the extracellular Na+ release.
Afterwards, the pump binds 2 extracellular K+ ions, which
facilitates the de-phosphorylation of the pump, reverting it to its original
conformational state, transporting the K+ ions to the cell interior. As the
de-phosphorylated form of the pump has a low affinity for K+ ions, this allows
the intracellular K+ release.
Na+ /K+ ATPase helps to maintain the resting membrane
potential and effective transport across the cell membrane, and accordingly,
regulates the cellular volume.
Resting Potential: In order to maintain the physiological
cell membrane potential, the intracellular concentrations of Na+ and K+ are
kept under a physiological balance, where a low concentration of Na+ and high
levels of K+ are favored. As the Na+ /K+ ATPase moves 3 Na+ out and 2 K+ in,
thus, in total, removing one positive charge from the intracellular space, this
creates a differential resting membrane potential between the cell membrane
interior and exterior. Disturbance of this physiological balance, through the
intracellular flow of Na+ , results in cell membrane depolarization
