NaKATPase

Na+/K+-ATPase, also known as NaKATPase, is a membrane-bound enzyme that uses energy from ATP hydrolysis to actively transport three sodium ions out of the cell and two potassium ions into the cell against their electrochemical gradients. This electrogenic pumping establishes and maintains the gradients essential for numerous cellular processes.

In animal cells, the pump comprises a catalytic alpha subunit and a glycoprotein beta subunit; several alpha (ATP1A1-ATP1A4) and beta (ATP1B1-ATP1B3) isoforms provide tissue-specific properties. A gamma subunit of the FXYD family can modulate activity in some tissues. The pump is a P-type ATPase with cytosolic domains that bind Na+, K+, and ATP.

It operates through an E1–E2 conformational cycle: binding three Na+ ions from the cytosol, phosphorylation of a conserved aspartate residue by ATP, a conformational change that releases Na+ to the outside, binding of two K+ from the exterior, dephosphorylation, and return to the original conformation to release K+ inside. The cycle couples ATP hydrolysis to ion transport, yielding an energy use that maintains ion gradients and membrane potential.

The pump maintains resting membrane potential, cell volume, and provides driving force for secondary active transport. In cardiac and nervous tissue, it influences excitability and contractility and can participate in signaling pathways independent of ion transport. It is inhibited by cardiac glycosides such as ouabain and digoxin; activity is modulated by hormones and intracellular Na+ and K+ levels.

Genetic mutations in ATP1A2 and ATP1A3 are associated with neurological disorders including familial hemiplegic migraine and rapid-onset dystonia-parkinsonism, while other mutations affect neuronal function.