1. Definition
The sodium-potassium ATPase (more precisely: Na+/K+-ATPase), is a transmembrane protein anchored in the cell membrane. The enzyme catalyzes the transport of sodium ions out of the cell and the transport of potassium ions into the cell, against the concentration gradient, by hydrolyzing ATP (ATPase).
2. Structure of the Sodium-Potassium Pump
The pump consists of two main subunits:
2.1. α-subunit: This is the larger catalytic subunit where the binding sites for Na⁺, K⁺, and ATP are located. It spans the membrane and is responsible for the ion exchange.
2.2. β-subunit: This smaller subunit stabilizes the pump and helps it in proper membrane insertion.
There are also regulatory γ-subunits in some forms of the pump, but these are not essential for the core function.
3. Cycle of the Sodium-Potassium Pump
The activity of the pump can be broken down into several key steps:
1. Binding of Sodium (Na⁺):
• The pump starts in its “E1” conformation, where it faces the inside of the cell.
• Three Na⁺ ions bind to specific sites on the intracellular side of the α-subunit.
2. Phosphorylation:
• ATP binds to the pump and is hydrolyzed, releasing energy.
• This energy causes the pump to phosphorylate itself (a phosphate group from ATP attaches to the pump), leading to a conformational change.
3. Conformational Change and Na⁺ Release:
• The pump shifts to the “E2” conformation, which opens towards the extracellular side of the membrane.
• This conformational change causes the three bound Na⁺ ions to be released into the extracellular space.
4. Binding of Potassium (K⁺):
• Two K⁺ ions from the outside of the cell now bind to their respective sites on the pump.
5. Dephosphorylation:
• The phosphate group that was attached during phosphorylation is removed.
• This triggers another conformational change, returning the pump to its original “E1” state, facing the intracellular side.
6. Release of K⁺:
• As the pump reverts to the “E1” conformation, the two K⁺ ions are released into the cytoplasm.
• The pump is now ready for another cycle.
This cycle can occur up to 300 times per second!
4. Summary of the Ion Exchange
For each cycle, the pump exports 3 Na⁺ ions out of the cell and imports 2 K⁺ ions into the cell.
5. Role in the resting potential
The transport protein actively counteracts charge equalization through its pumping process. This enables the cell to maintain a negative voltage (= resting potential). This is particularly important for nerve cells, which also explains why around 50-70% of the total energy turnover is used for the sodium-potassium pump in them.
6. Pharmacology
6.1. Stimulation:
– Insulin
– Adrenaline
A stimulation promotes hypokalemia.
6.2. Inhibition:
– Quabain
– Cardiac glycosides (digitalis)
An inhibition promotes hyperkalemia.