Sarcoplasmic of muscle

The sarcoplasmic reticulum is a fine reticular network of membrane-limited elements, which pervades the sarcoplasm of muscle cells. 

Any dialogue on meat flavor development and deterioration requires a brief discussion of muscle structure. Muscle has a highly compact and complex multicellular structural organization (Figure 2). Individual muscle cells contain numerous mitochondria and nuclei. They also contain contractile elements as the bulk of their structure. While the sarcoplasm of muscle (the aqueous non-organellar component) is small compared to the cytoplasm of non-muscle cells, it does have a highly evolved system of membranes called the SR/L representing an acronym for sarcoplasmic reticulum/lysosomal membrane system (11). The SR/L surrounds each contractile element (Fig. 9-13 in 12 Fig. 7-10 in 13). The close proximity of the SR/L to the contractile proteins situates the proteins in a location that is optimal for their hydrolysis by lysosomal hydrolases (12, 13). 

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). 

In the sarcoplasm of smooth muscle cells there is a membrane bound compartment usually referred to as the SR by analogy with skeletal muscle. However, it is not at all clear that the interior of these membrane-bound regions are continuous as they are in skeletal muscle. The primary properties of this system seem to be quite similar to those of the endoplasmic reticulum of many other cell types. In general, calcium is concentrated into the membrane-bound reticulum and then released to initiate the characteristic action of the cell. 

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

In the sarcoplasm of resting muscle, the concentration of Ca + is 10 to 10 mol/L. The resting state is achieved because Ca + is pumped into the sarcoplasmic reticulum through the action of an active transport system, called the Ca + ATPase (Figure 49-8), initiating relaxation. The sarcoplasmic reticulum is a network of fine membranous sacs. Inside the sarcoplasmic reticulum, Ca + is bound to a specific Ca -binding protein designated calsequestrin. The sarcomere is surrounded by an excitable membrane (the T tubule system) composed of transverse (T) channels closely associated with the sarcoplasmic reticulum. 

The general picture of muscle contraction in the heart resembles that of skeletal muscle. Cardiac muscle, like skeletal muscle, is striated and uses the actin-myosin-tropomyosin-troponin system described above. Unlike skeletal muscle, cardiac muscle exhibits intrinsic rhyth-micity, and individual myocytes communicate with each other because of its syncytial nature. The T tubular system is more developed in cardiac muscle, whereas the sarcoplasmic reticulum is less extensive and consequently the intracellular supply of Ca for contraction is less. Cardiac muscle thus relies on extracellular Ca for contraction if isolated cardiac muscle is deprived of Ca, it ceases to beat within approximately 1 minute, whereas skeletal muscle can continue to contract without an extraceUular source of Ca +. Cyclic AMP plays a more prominent role in cardiac than in skeletal muscle. It modulates intracellular levels of Ca through the activation of protein kinases these enzymes phosphorylate various transport proteins in the sarcolemma and sarcoplasmic reticulum and also in the troponin-tropomyosin regulatory complex, affecting intracellular levels of Ca or responses to it. There is a rough correlation between the phosphorylation of Tpl and the increased contraction of cardiac muscle induced by catecholamines. This may account for the inotropic effects (increased contractility) of P-adrenergic compounds on the heart. Some differences among skeletal, cardiac, and smooth muscle are summarized in... 

Our discussion here will concentrate on the various forms of the Ca " transport ATPases that occur in the sarcoplasmic reticulum of muscle cells of diverse fiber types and in the endoplasmic reticulum of nonmuscle cells (SERCA). The structure of these enzymes will be compared with the Ca transport ATPases of surface membranes (PMCA) [3,29-32,34] and with other ATP-dependent ion pumps that transport Na, K, andH [46,50-52]. 

Second-line Dantrolene Direct inhibitor of muscle contraction by decreasing the release of calcium from skeletal muscle sarcoplasmic reticulum 25 mg orally daily, increase to 25 mg 3-4 times daily, then increase by 25 mg every 4-7 days to a maximum of 400 mg/day... 

All types of muscle require calcium for contraction. In skeletal muscle, Ca++ ions are stored within an extensive membranous network referred to as the sarcoplasmic reticulum. This network is found throughout the muscle fiber and surrounds each myofibril. Furthermore, segments of the sarcoplasmic reticulum lie adjacent to each T tubule that, with a segment of sarcoplasmic reticulum on either side of it, is referred to as a triad. As the action potential is transmitted along the T tubule, it stimulates the release of Ca++ ions from the sarcoplasmic reticulum. The only source of calcium for skeletal muscle contraction is the sarcoplasmic reticulum. 

When the action potentials in the alpha motor neuron cease, stimulation of muscle fiber is ended. Ca++ ions are pumped back into the sarcoplasmic reticulum and troponin and tropomyosin return to their original positions. As a result, the myosin-binding sites on the actin are covered once again. The thin filaments return passively to their original positions, resulting in muscle relaxation. 

Devine CE, Somlyo AV, Somlyo AP 1971 Sarcoplasmic reticulum and excitation-contraction coupling in mammalian smooth muscles. J Cell Biol 52 690-718 Ebashi S 1991 Excitation—contraction coupling and the mechanism of muscle contraction. Annu Rev Physiol 53 1—16... 

The sarcoplasmic reticulum (SR) functions to uptake calcium from the sarcoplasm (the cytoplasm of muscle fiber). The sarcoplasmic reticulum... 

Krenacs, T., Stiller, D., Krenacs, L., Bahn, H., Molnr, F., and Dux, L. (1990) Sarcoplasmic reticulum (SR) Ca +-ATPase as a marker of muscle-cell differentiation immunohistochemical investigations of rhabdomyosarcomas and enhancement of immunostaining after sodium methoxide treatment. Acta Histochem. 88, 159-166. 

Figure 13.16 A summary of the control of muscle contraction by the motor neurone. When an electrical impulse arrives at the junction between a nerve axon and a muscle fibre, a small amount of acetylcholine is released. This initiates an action potential which is transmitted throughout the fibre via the T-tubules. This causes the sarcoplasmic reticulum to release Ca ions which initiate contraction of the myofibrils via changes in troponin and tropomyosin. Thus sites on the actin for binding of the myosin cross-bridges are exposed.

Studies of the efflux of Ca by stimulated rabbit atria have characterized three calcium pools. Phase I may represent extracellular washout of the Ca that binds to the surface of muscle membrane and is characterized by a high rate constant. Phase II may represent loosely bound calcium present in cell membrane and calcium released at the sarcoplasmic reticulum. Calcium in this pool is directly related to contractility.65,84,93 phase III may represent the tightly bound calcium that exchanges very slotrly and does not play a role in maintaining calcium concentrations. Recent study has shown that the storage or release of calcium at the sarcoplasmic reticulum and other loosely bound calcium sites (cell membrane) that are involved in muscle contractility can be directly affected by 2-PAM.21 These results Indicate that 2-PAM increases the rate of release of Phase II calcium. 

It has been postulated that 2-PAM exerts its cardiac action in rabbit atria through its alteration of calcium metabolism. The relaxation phase of skeletal muscle contraction seems to be directly affected by the sarcoplasmic reticulum because of its ability to sequester calcium actively.29,46 a similar role has been suggested for the sarcoplasmic reticulum in cardiac muscle. 6,83 The onset of muscle contraction takes place when calcium reaches a crit-cal concentration. This contraction is later reduced by the increased calcium-sequestering activity of the sarcoplasmic reticulum. Thus, 2-PAM can affect this process by decreasing the rate of calcium uptake by the sarcoplasmic reticulum, which results in increasing the time required to reduce the calcium concentration enough to allow relaxation to take place. This was demonstrated by the Increase in the relaxation phase. It was suggested that this... 

In contrast to milk, where samples are primarily derived from cows, meat analysis has to be performed in samples of a widely different animal origin including cattle, lamb, swine, poultry, and fish. Muscle is a complex matrix with a pH of 5.7, composed of muscle fibers, various types of connective tissue, adipose tissue, cartilage, and bones. Sarcoplasmic proteins such as myoglobin, and glycolytic enzymes are soluble in water while the myofibrillar proteins such as myosin and actin are soluble in concentrated salt solutions (14). The connective tissue proteins, collagen and elastin, are insoluble in both solvents. 

The identification of the sarcoplasmic reticulum membranes as the intracellular calcium transport system involved in the regulation of muscle activity took considerable time and occurred at first quite fortuitously. Kielley and Meyerhof40, not aware of the existence of the sarcoplasmic reticulum, characterized it biochemically as an... 

Skeletal muscles consist of bundles of long muscle fibers, which are single cells of diameter 10-100 pm formed by the fusion of many embryonic cells. The lengths are typically 2-3 cm in mammals but may sometimes be as great as 50 cm. Each fiber contains up to 100-200 nuclei. Typical cell organelles are present but are often given special names. Thus, the plasma membrane (plasmalemma) of muscle fibers is called the sarcolemma. The cytoplasm is sarcoplasm, and mitochondria may be called sarcosomes. The major characteristic of muscle is the presence of the contractile myofibrils, organized bundles of proteins 1-2 pm in diameter and not separated by membranes from the cytoplasm. Since they occupy most of the cytoplasm, a substantial number of myofibrils are present in each muscle fiber. 

The role of calcium in this function is not fully understood. Some researchers have proposed that calcium is the link bciwccn the electrical and mechanical events in contraction. It has been shown b vitro that when calcium ions are applied locally, muscle fibers can be triggered to contract. It has further been postulated that relaxation of muscle libels is brought about by an intracellular mechanism for reducing the coneentraliun of calcium ions availahle lo ihe muscle h lamenls. Others postulate thai contraction occurs because calcium inactivates a relaxing substance, which is released front the sarcoplasmic reticulum in the presence of ATP (adenosine iriphosphate). 

Figure B3.1.1 A 15% SDS-polyacrylamide gel stained with Coomassie brilliant blue. Protein samples were assayed for the purification of a proteinase, cathepsin L, from fish muscle according to the method of Seymour et al. (1994). Lane 1, purified cathepsin L after butyl-Sepharose chromatography. Lane 2, cathepsin L complex with a cystatin-like proteinase inhibitor after butyl-Sepharose chromatography. Lane 3, sarcoplasmic fish muscle extract after heat treatment and ammonium sulfate precipitation. Lane 4, sarcoplasmic fish muscle extract. Lanes M, low-molecular-weight standards aprotinin (Mr 6,500), a-lactalbumin (Mr 14,200), trypsin inhibitor (Mr 20,000), trypsinogen (Mr 24,000), carbonic anhydrase (Mr 29,000), gylceraldehyde-3-phosphate dehydrogenase (Mr 36,000), ovalbumin (Mr 45,000), and albumin (Mr 66,000) in order shown from bottom of gel. Lane 1 contains 4 pg protein lanes 2 to 4 each contain 7 pg protein.

The carrier-mediated active transport system of calcium is responsible for the relaxation of muscle. However, the rate of efflux from sarcoplasmic reticulum membranes during reversal of the transport process is 102 to 104 orders too low to account for the massive calcium release from sarcoplasmic reticulum in stimulated muscle. Instead, passive diffusion of calcium across the sarcoplasmic reticulum membrane will proceed during excitation of muscle178,179,186. The rate of calcium release observed during excitation is 1.000-3.000 p moles/mg protein/min which is an increase of about 104 to 10s over the resting state. 

Franzini-Armstrong, C. (1999). The Sarcoplasmic Reticulum and the Control of Muscle Contraction. Faseb J 13 Suppl 2 S266-70. 

Rossi, A. E., and Dirksen, R. T. (2006). Sarcoplasmic Reticulum the Dynamic Calcium Governor of Muscle. Muscle Nerve 33(6) 715-31. 

The increased availability of calcium within the cardiac cell enables it to store more calcium in the sarcoplasmic reticulum.60 As in any type of muscle cell, calcium is normally stored within the sarcoplasmic reticulum and released during each action potential to facilitate actin-myosin... 

Flavonoids can affect the function of plasma membrane transport Na+- and K+-ATPase, mitochondrial ATPase, and Ca2+-ATPase. The Mg2+-ectoATPase of human leukocytes is inhibited by quercetin, which acts as a competitor of ATP binding to the enzyme. The sarcoplasmic reticulum Ca2+-ATPase of muscle is effectively inhibited by several flavonoids that were also active inhibitors of antigen-induced mast cell histamine release. 

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