The Sodium-Potassium Pump

• The Sodium-Potassium pump is present in the cell membrane and are trans-membrane complexes of proteins.
• The active transporter uses energy directly from the cell metabolism.
• The pump consists of two globular proteins, alpha and beta components
• The alpha proteins are larger (100,000), and the beta proteins are smaller (55000)
• The ten-pass protein (alpha unit): The pump action is performed by the alpha, unit of the Sodium-Potassium pump, which spans the membrane ten times.

Introduction

• Function: The most important function of this pump is the expulsion of Sodium from the cell.
• During one pump cycle, it expels 3 Sodium and imports 2 Potassium simultaneously.
• This pump utilizes up to 25% of the energy produced in the body and up to 70% of the energy produced in the CNS.
• The energy used for the pump's functioning is derived from ATP, so it is also called ATPase or Sodium Potassium - ATPase pump.
• Outside the cells, sodium is high, so these pumps move the three sodium against their concentration (extracellular Sodium concentration is 140 mEq/L) and an electrical gradient: This type of transport is termed active transport.
• The pump also pumps the 2 Potassiums against their concentration gradient (extracellular concentration is 4 mEq/L) out of the cells.
• The pump is an active transporter because the energy used for this active transport comes from the direct metabolism in the cell so these pumps are also called primary active transporters.
• During each pump cycle, one sodium ion and two potassium ions move into the cell, while one cation is lost from the interior side of the membrane: As a result, the inside of the cell becomes deficient in positive ions, leading to a slightly negative charge so a potential difference is created across the membrane as the pump operates and is considered electrogenic.
• Numerous pumps exist within each body cell, particularly in myocardial and neuronal cells in even greater quantities to facilitate various cellular activities.
• These pumps continuously transport sodium out of the cells while bringing potassium into them, which leads to cells being considered as bags of potassium surrounded by extracellular fluid rich in sodium.
• If there is significant destruction Hyperkalemia because a large amount of potassium will be released into the bloodstream: This can occur in situations such as Crush injuries, extensive surgeries, burns, hemolysis, septicemia, and tumor lysis syndrome, among others.

Structure of the Sodium-Potassium Pump

• These pumps are present in the cell membranes of all animal cells.
• The pump consists of two globular proteins, alpha and beta components with the alpha proteins are larger (100,000), and the beta proteins are smaller (55000) so these pumps are hetero-dimeric.
• The alpha unit is important in the pump function and consists of a long peptide chain, spans the cell membrane about ten times forming a ten-pass protein and the amino and carboxyl ends are both intracellular.
• The alpha unit performs the real pump action and ATP breakdown unit, with a sodium binding site internally and a potassium binding site externally, is phosphorylated, so it is a P-type pump. It also has binding sites for the ATP, ATPase, and inorganic phosphate.
• The pump works some pumps only operate when they break down the ATP into ADP and hold the phosphate, only then are they functional.
• The smaller beta subunit passes only once through the membrane, assists in the folding, targeting, and anchoring of the alpha unit in the membrane.

Function of the Sodium-Potassium Pump

• The pump's alpha unit has two configurations: The mouth open inside and the mouth open outside.
• The pump consists of two globular proteins, alpha & beta components, with the alpha proteins being larger (100,000), and the beta proteins being smaller (55000).
• Alpha and beta subunits are both important to the pump function and consist of a long polypeptide chain with 10 passes through the cell membrane; the C and N terminals are both intracellular.
• The pump works when phosphorylated, so it is a P-type pump with ATPase activity: ATP>ADP+Pi
• Numerous pumps exist within the body, particularly in the myocardial and neuronal cells. The pump action performs by the alpha unit spans the membrane ten times.
• Firstly, the alpha unit of the Sodium Potassium pump, with its gate opened inside, with the ATP at the ATP binding site, making the alpha unit in the E-1 state known as E1+ ATP then after binding with the ATP, sodium binding domains are converted into a high-affinity state.
• Next, sodium will attach to the special pockets, sodium binding domains on the alpha unit, three sodium ions will bind with the alpha unit's sodium binding domains: This will convert the ATP-loaded E-1 state into an ATP and 3 Sodium-loaded Es state.
• The alpha unit's mouth inside the cell opens and closes with sodium ions in the sodium binding domains, preventing the sodium ions from back-flowing inside the cell which is called the E-1 state with ATP, 3 Sodium, and internal obstruction, as E1+Pi.3Na E2 + Pi.3Na'.
• The ATPase domain on the alpha unit is activated and will kick over to the ATP site, removing the ADP with the terminal phosphate bond of ATP breaks down, the energy release goes to the pump, and the terminal phosphate stays attached to the alpha unit called phosphorylation point.
• Once the pump is phosphorylated, the pump will move from the E-1 state to the E-2 confirmation state which is where the membrane mouth is open on the outside with less affinity for sodium.
• In the E-2 phosphorylated state, the affinity for the sodium ions becomes less and will lose the sodium ions through the outside open mouth.
• This is when the sodium ions are lost, the potassium binding sites at a low-affinity state will move to the high-affinity state making it the E-2 phosphorylated state with a high affinity for the potassium ions (E2. Pi.2 Potassium).
• As soon as the potassium ions are loaded, the E-2 state will undergo occlusion as E2 Pi 2 Potassium occluded.

Regulation of the Sodium-Potassium Pump

• Sodium Potassium pump activity can be altered by increasing or decreasing the number of pumps per cell through genetic change, or altering the phosphorylation and dephosphorylation of the pump and changing its function.
• The following factors can regulate the Sodium Potassium -ATPase functions Thyroid hormones, Aldosterone, Insulin and Dopamine.
• The phosphorylation and dephosphorylation of the pump change its function and the thyroid hormone, Insulin, aldosterone, catecholamines, and dopamine regulate the sodium-potassium pump and is regulated by hormones and neurotransmitters.