Calcium pump

There is a very large transmembrane electrochemical gradient of Ca2+ driving the entry of the ion into cells, yet it is very important for cells to maintain low concentrations of Ca2+ for proper cell signalling; thus it is necessary for the cell to employ ion pumps to remove the Ca2+.

The PMCA and the sodium calcium exchanger (NCX) are together the main regulators of intracellular Ca2+ concentrations.

Why cells need calcium pumps
Ca2+ has many important roles as an intracellular messenger. The release of a large amount of free Ca2+ can trigger a fertilized egg to develop, skeletal muscle cells to contract, secretion by secretory cells and interactions with Ca2+ -responsive proteins like calmodulin. To maintain low concentrations of free Ca2+ in the cytosol, cells use membrane pumps like calcium ATPase found in the membranes of sarcoplasmic reticulum of skeletal muscle. These pumps are needed to provide the steep electrochemical gradient that allows Ca2+ to rush into the cytosol when a stimulus signal opens the Ca2+ channels in the membrane. The pumps are also necessary to actively pump the Ca2+ back out of the cytoplasm and return the cell to its pre-signal state.

Muscle cells need calcium pumps
An impulse from a motor neuron causes stimulus of a muscle cell by acetylcholine. In response, the muscle cell allows an influx of sodium ions, which then stimulate a muscle impulse. The muscle cell’s sarcoplasmic reticulum responds to this impulse by becoming more permeable to Ca2+. The diffusion of Ca2+ into the muscle fiber’s cytoplasm allows the Ca2+ to bind to the troponin of the muscle’s thin filament. This binding triggers events with the fiber’s filaments that result in a contraction cycle. When the acetylcholine is decomposed, the membrane’s permeability decreases. The calcium ATPase pumps actively transport the Ca2+ back into the sarcoplasmic reticulum starting the events which relax the muscle.

Understanding calcium pumps through crystallography
Experimental work in crystallography done by Chikashi Toyoshima and colleagues provides a model of the calcium ATPase pump found in skeletal muscle sarcoplasmic reticulum. Calcium ATPase is a member of the P-type ATPases that transport ions across a membrane against a concentration gradient. The scientists used microscopy of tubular crystals and 3D microcrystals to study this protein’s structure. The pump has a molecular mass of 110,000, shows three well separated cytoplasmic domains, with a transmembrane domain consisting of ten alpha helices, and two transmembrane binding sites for the Ca2+.

How the calcium pump works
Classical Theory of active transport for P-type ATPases Data from crystallography studies by Chikashi Toyoshima applied to the above cycle