Skeletal muscle calcium pump

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. 

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... 

Genetic evidence supports the importance of coordinated expression and distributions of a2 or a3 Na+/K+ pump isoforms with the Na+/Ca2+ exchanger (NCX) and Ca2+ pumps to function in excitable and contractile cells deletion of one copy of the a2 Na+/K+ pump gene in mice leads to increased contractile force in cardiac and skeletal muscle while deletion of one copy of the al gene leads to reduction of contractile force [25]. In rat optic nerve astrocytes, deletion of the a2 gene or ouabain treatment of cells expressing a2 leads to increased capacitative calcium entrance responses, which reflect a decreased ability to rapidly remove cytosolic Ca2+ [26]. 

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... 

The best studied example of a Group IIA cation transport system is the calcium pump of the sarcoplasmic reticulum of skeletal muscle. Indeed, the calcium pump and the sodium pump represent the most studied of all transport processes. The calcium pump involves a membrane-bound (Ca2+, Mg2+)-ATPase and uptake of Ca2+ is associated with hydrolysis of ATP. While the... 

The Ca -ATPase piays an essential role In the pumping of calcium out of cells, and in the control of its cytosolic concentration. In the heart, the role of the pump is minor with respect to that of the sodium-calcium exchanger, but is most probabiy predominant in skeletal and smooth muscle. The pump is encoded by four independent genes, showing different patterns of tissue-specific expression and alternative splicing of the primary transcripts. The intracellular Ca pump proteins from skeletal muscle sarcoplasmic reticulum (SR), cardiac SR and brain microsomes are similar. Thapsigargin is a potent inhibitor, also lanthanum salts inhibit the pump at most sites. 

Muscle cells contain many mitochondria which are often present as reticulum-like structures extending longitudinally in the fiber near the sarcolemma, rather than as discrete ellipsoidal organelles found in many other cells. These provide much of the high-energy phosphate needed to power contraction and to operate the Ca + pumps that control the cytosolic calcium concentration. Different types of skeletal muscle fibers differ considerably in the extent and organization of both their SR and mitochondria. 

In the cytosol of muscle cells, the free Ca " ranges from 10 M (resting cells) to more than 10 (contracting cells), whereas the total Ca concentration In the SR lumen can be as high as 10 M. However, two soluble proteins In the lumen of SR vesicles bind Ca " and serve as a reservoir for intracellular Ca ", thereby reducing the concentration of free Ca " ions In the SR vesicles and conse-quendy the energy needed to pump Ca " ions into them from the cytosol. The activity of the muscle Ca " ATPase increases as the free Ca " concentration in the cytosol rises. Thus in skeletal muscle cells, the calcium pump in the SR membrane can supplement the activity of a similar Ca " pump located in the plasma membrane to assure that the cytosolic concentration of free Ca " in resting muscle remains below 1 jjlM. 

The rapid decrease in the level of ATP following death has two consequences. First, the cytosolic level of calcium rises rapidly because the Ca i-ATPase pumps in the plasma membrane and sarcoplasmic reticulum membrane no longer operate. High Ca, through troponin and tropomyosin, enables myosin to interact with actin. Second, a large proportion of SI heads -will be associated with actin. Recall that ATP is required to dissociate the actomyosin complex. In the absence of ATP, skeletal muscle is locked in the contracted (rigor) state. 

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