Thursday, 4 August 2016

Regenerative Therapy in Autosomal Recessive Polycystic Kidney Disease


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

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