Sunday, October 24, 2010

So, what exactly is a Na+/K+-ATPase

With all that many blogs thus far dedicated to this ATPase, I just realized maybe not everyone knows what a Na+/K+-ATPase is or what it does. Well, for those who are not as familiar with the Na+/K+-ATPase, here is a short background for ya.

The Na+/K+-ATPase, is a small, but nonetheless important membrane-bound active ion-transporter protein that is expressed in all multicellular organisms. This ATPase belongs the P-type ion-motive APTase family, in which also contains other H+, H+/K+, Ca2+, and heavy metal pumps. The Na+/K+-ATPase is a heterodimer containing alpha- and beta-subunits. The alpha-subunit is the catalytic subunit with a size of approximately 100kDa. In mammals, it has been noted the ATPase is composed of at least three a-subunits and three b-subunits. However, there is no evidence indicating the expression of different isoforms in insects, which is the one I'm studying. The active transport of ions across membranes by this ATPase is the greatest single energy-consuming process in most cells. Depending on the tissue type, the Na+/K+-ATPases consume between 5 – 40% of the cellular energy expenditure. Thus despite its small size, the Na+/K+-ATPase is a very important protein, especially in sensor/nervous/muscular cells where it is essential in conducting action potentials, and in renal cells where it regulates the reaborption of sodium.


 The key roles of this ATPase include, but not limited to regulating cell volume regulation, providing ion gradients that facilitate the movement of other solutes, and acting as a physiological regulator. Moreover, researchers have also demonstrated that in cardiac muscles, the Na+/K+-ATPase can even act as an indirect regulator of the myocardium contraction. In addition, the ion gradients provided by the ATPase across plasmalemmal membranes are also critical to cells, especially to those sensory, muscular and nervous cells.


Balanced Na+ and K+ ion-gradients across the neuronal membranes are essential for neurons to generate and conduct action potentials along their axons. The Na+/K+-ATPase assists neurons to sustain their Na+ and K+ homeostasis by shuffling Na+ and K+ ions across the plasma membranes. Through per ATP expenditure, this ion-transporter protein exports 3 Na+ ions out to the extracellular space for every 2 K+ ions imported into the cytoplasm. Due to the vital role of the Na+/K+-ATPase in sustaining action potentials, which is depended on the establishment of the Na+ and K+ homeostasis across the cellular membranes, the activity of this ATPase is targeted by multiple regulatory mechanisms to ensure its correct functioning. Failure in the regulatory mechanisms would often lead to deleterious effects.

 
To ensure its survival, a cell has overlapping mechanisms to failproof its regulations on the Na+/K+-ATPase. For example, the ATPase activity is enhanced by its substrates, or inhibited by cardiac glycosides. In addition, the Na+/K+-ATPase enzyme and substrate affinity also varies according to the cellular environment. Researchers have demonstrated that the addition of cytoskeletal proteins can increase the affinity of Na+/K+-ATPase for ATP. Furthermore, various hormones, such as insulin, and other signalling molecules can affect the activity of the protein positively or negatively. Moreover, the activity of the ATPase is also subject to regulation by reversible protein phosphorylation.

As you can sell, despite the relatively small size of the Na+/K+-ATPase, the rigorousity of the mechanisms that are regulating the Na+/K+-ATPase is undeniable. These mechanisms proved the importance of this protein and ensured that it is always being kept under its optimal condition to maintain the Na+ and K+ ion-gradients, a duty that is critical to an organism’s survival.

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