Calcium sarcoplasmic pump

Calcium is pumped back into the sarcoplasmic reticulum. This requires adenosine triphosphate (ATP). 

The cytosolic concentration of free Ca2+ is generally at or below 100 mi, far lower than that in the surrounding medium, whether pond water or blood plasma. The ubiquitous occurrence of inorganic phosphates (Pj and I l ,) at millimolar concentrations in the cytosol necessitates a low cytosolic Ca2+ concentration, because inorganic phosphate combines with calcium to form relatively insoluble calcium phosphates. Calcium ions are pumped out of the cytosol by a P-type ATPase, the plasma membrane Ca2+ pump. Another P-type Ca2+ pump in the endoplasmic reticulum moves Ca2+ into the ER lumen, a compartment separate from the cytosol. In myocytes, Ca2+ is normally sequestered in a specialized form of endoplasmic reticulum called the sarcoplasmic reticulum. The sarcoplasmic and endoplasmic reticulum calcium (SERCA) pumps are closely related in structure and mechanism, and both are inhibited by the tumor-promoting agent thapsigargin, which does not affect the plasma membrane Ca2+ pump. 

Toyoshima, C., Sasabe, H., Stokes, D.L. (1993). Three-dimensional cryo-electron microscopy of the calcium ion pump in the sarcoplasmic reticulum membrane. Nature (London) 362,469-471. 

Calcium plays a vitally important part in possibly as many as three sequences of the contraction—relaxation cycle of vertebrate muscle (Taylor, Lymn and Moll, 1970). In the sarcoplasmic reticulum, calcium is stored in calsequestrin, a protein which holds, with high affinity, 43 atoms of calcium per molecule. The calcium is released in response to nervous impulses and triggers a sequence of reactions that lead to contraction of the muscle. After the contraction, the calcium is pumped back into this reticulum by the calcium/magnesium-dependent ATPase. 

Contraction of muscle follows an increase of Ca " in the muscle cell as a result of nerve stimulation. This initiates processes which cause the proteins myosin and actin to be drawn together making the cell shorter and thicker. The return of the Ca " to its storage site, the sarcoplasmic reticulum, by an active pump mechanism allows the contracted muscle to relax (27). Calcium ion, also a factor in the release of acetylcholine on stimulation of nerve cells, influences the permeabiUty of cell membranes activates enzymes, such as adenosine triphosphatase (ATPase), Hpase, and some proteolytic enzymes and facihtates intestinal absorption of vitamin B 2 [68-19-9] (28). 

The trigger for all musele eontraetion is an increase in Ca eoneentration in the vicinity of the muscle fibers of skeletal muscle or the myocytes of cardiac and smooth muscle. In all these cases, this increase in Ca is due to the flow of Ca through calcium channels (Figure 17.24). A muscle contraction ends when the Ca concentration is reduced by specific calcium pumps (such as the SR Ca -ATPase, Chapter 10). The sarcoplasmic reticulum, t-tubule, and sarcolemmal membranes all contain Ca channels. As we shall see, the Ca channels of the SR function together with the t-tubules in a remarkable coupled process. 

Sarcoplasmic calcium ATPase this enzyme utilizes the energy gained from hydrolysis of ATP to pump calcium from the cytosol into the stores of the sarcoplasmic reticulum. Its activity is negatively regulated by the closely associated protein phospholamban, and this inhibition is relieved upon phosphorylation of phospholamban by protein kinase A (PKA). 

Site symmetry symbols, I, 128 Six-coordinate compounds stereochemistry, 1, 49-69 Six-membered rings metal complexes, 2, 79 Skeletal muscle sarcoplasmic reticulum calcium pump, 6, 565 Slags... 

Fast-twitch muscle fibers develop tension two to three times faster than slow-twitch muscle fibers because of more rapid splitting of ATP by myosin ATPase. This enables the myosin crossbridges to cycle more rapidly Another factor influencing the speed of contraction involves the rate of removal of calcium from the cytoplasm. Muscle fibers remove Ca++ ions by pumping them back into the sarcoplasmic reticulum. Fast-twitch muscle fibers remove Ca++ ions more rapidly than slow-twitch muscle fibers, resulting in quicker twitches that are useful in fast precise movements. The contractions generated in slow-twitch muscle fibers may last up to 10 times longer than those of fast-twitch muscle fibers therefore, these twitches are useful in sustained, more powerful movements. 

Calcium ions are actively pumped back into the extracellular fluid as well as the sarcoplasmic reticulum. When the concentration of calcium falls below... 

The smooth endoplasmic reticulum calcium pumps (SERCA) found in brain were first identified in sarcoplasmic reticulum. The three isoforms of SERCA are products of separate genes SERCA-1 is expressed in fast-twitch skeletal muscle SERCA-2a in cardiac/slow-twitch muscle SERCA-2b, an alternatively spliced form, is expressed in smooth muscle and non-muscle tissues SERCA-3 is... 

Mehorta and coworkers (1989) observed that isolated fractions of brain and heart cells from rats orally administered 0.5-10 mg endrin/kg showed significant inhibition of Ca+2 pump activity and decreased levels of calmodulin, indicating disruption of membrane Ca+2 transport mechanisms exogenous addition of calmodulin restored Ca+2-ATPase activity. In vitro exposure of rat brain synaptosomes and heart sarcoplasmic reticuli decreased total and calmodulin-stimulated calcium ATPase activity with greater inhibition in brain preparations (Mehorta et al. 1989). However, endrin showed no inhibitory effects on the calmodulin-sensitive calcium ATPase activity when incubated with human erythrocyte membranes (Janik and Wolf 1992). In vitro exposure of rat brain synaptosomes to endrin had no effect on the activities of adenylate cyclase or 3, 5 -cyclic phosphodiesterase, two enzymes associated with synaptic cyclic AMP metabolism (Kodavanti et al. 1988). 

ATP is used not only to power muscle contraction, but also to re-establish the resting state of the cell. At the end of the contraction cycle, calcium must be transported back into the sarcoplasmic reticulum, a process which is ATP driven by an active pump mechanism. Additionally, an active sodium-potassium ATPase pump is required to reset the membrane potential by extruding sodium from the sarcoplasm after each wave of depolarization. When cytoplasmic Ca2- falls, tropomyosin takes up its original position on the actin and prevents myosin binding and the muscle relaxes. Once back in the sarcoplasmic reticulum, calcium binds with a protein called calsequestrin, where it remains until the muscle is again stimulated by a neural impulse leading to calcium release into the cytosol and the cycle repeats. 

Garcia M, Gonzalez R. 1985. Uncoupling of the calcium pump of the sarcoplasmic reticulum by kerosene. Toxicol Lett 28(l) 59-64. 

Jencks has considered the mechanism of action of the sarcoplasmic reticulum calcium pump, which catalyzes the following reaction ... 

Cellular calcium regulation. Depicted are several sites that control calcium entry, efflux, and sequestration. 1. Na+, Ca++ exchange. 2. Receptor-operated channels. 3. Voltagegated channels. 4. Leak pathways. 5, 6. Entry and efflux in sarcoplasmic reticulum. 7. Plasma membrane pump. 

Schematic diagram of a cardiac muscle sarcomere, with sites of action of several drugs that alter contractility. Na+,K+ ATPase, the sodium pump, is the site of action of cardiac glycosides. NCX is the sodium, calcium exchanger. Cav-L is the voltage-gated, L-type calcium channel. SERCA (sarcoplasmic...

Sodium and potassium are not the only ions which can participate in pumps and channels. Calcium is also pumped, channeled, exhanged,and stored. See Figure 23. Calcium concentration within the cell cytoplasm is very low. This allows the calcium to play a pivotal role in cellular activity. The cytoplasmic protein calmodulin binds and stores calcium ion. Various intracellular structures and organelles such as the mitochondria and sarcoplasmic reticulum also store calcium. Calcium is vital to such functions as the release of neurotransmitters from nerve cells. There are at least seven known modes of biochemical action for this ion, one of the most important of which involves stimulation of cardiac muscle protein (actin-myosin). Certain types of angina (heart pain) are believed to be caused by abnormal stimulation of cardiac arteries and muscle (coronary spasm) A relatively new class of drugs, known as the calcium channel blockers, has brought relief from pain and arrhythmias (irregular heart beats). 

Characterization of the Sarcoplasmic Reticulum Membranes and Their Calcium Pump... 

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