Skeletal muscle system

The situation concerning a possible role for free radicals in fatigue of skeletal muscle therefore remains unclear. Antioxidants may have some inhibitory role in fatigue of a diaphragm preparation but our experiments using a similar intact skeletal muscle system have not supported these conclusions. It is therefore possible that antioxidants are only beneficial where tissue viability is compromised. Further work is required to clarify this area. 

Figure 2.16. The effect of change in flux through the glycolytic path (low vs high work rates) for two (A trout muscle B rat gastrocnemius) skeletal muscle systems in vivo (modified from Hochachka, 1994) and (C) for perfused rat heart preparations in vitro (modified from Kashiwaya et al., 1994). One of the instructive insights arising from these kinds of studies is the so-called [s] stability paradox remarkably stable concentrations of pathway intermediates during changes in pathway fluxes that can approach or exceed 100-fold. See text for other details.

In its simplest form, actin (A) combines with myosin (M) and ATP to produce force, adenosine diphosphate (ADP) and inorganic phosphate. Scientists now agree that ATP serves at least two functions in skeletal muscle systems first, ATP disconnects actin from... 

Van VIeet JF, Ferrans V), Herman E Cardiovascular and skeletal muscle systems. In Handbook of Toxicologic Pathology. Edited by Haschek WM, Rousseaux CG. San Diego, Academic Press, 1991, pp 602-618,... 

AQP4 is the predominant water channel in the central nervous system (CNS), where it is involved in maintaining brain water balance and neural signal transduction. It is mainly expressed in astroglial cells, which support the neurons. Outside the CNS, AQP4 has been found in the basolateral membrane of renal principal cells as well as in various glandular epithelia, airways, skeletal muscle, stomach, retina and ear. 

Parvalbumin (Fig 1) is a cytosolic protein expressed in fast-twitch skeletal muscles and in the nervous system. In muscles, parvalbumin controls the relaxation process. In the CNS, parvalbumin, expressed in a subpopulation of GABAergic neurons, is correlated with their firing rates, protecting the cells from Ca2+ overload. 

NHE5. The distribution of this isoform is distinct, being in neuronal-rich areas of the central nervous system. Low levels have also been found in testis, spleen and skeletal muscle. Like the preceding isoforms, NHE5 is found in the plasma membrane and is internalised by clathrin-associated endocytosis into recycling endosomes. The normal role of NHE5 is unknown but its malfunction is speculated to contribute to the development of neurodegenerative disease. 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

The PNS is further divided into the somatic nervous system and the autonomic nervous system. The somatic branch of the PNS is concerned witii sensation and voluntary movement. The sensory part of the somatic nervous system sends messages to the brain concerning die internal and external environment, such as sensations of heat, pain, cold, and pressure The voluntary part of die somatic nervous system is concerned witii die voluntary movement of skeletal muscles, such as walking, chewing food, or writing a letter. 

The analytic validity of an abstract parallel elastic component rests on an assumption. On the basis of its presumed separate physical basis, it is ordinarily taken that the resistance to stretch present at rest is still there during activation. In short, it is in parallel with the filaments which generate active force. This assumption is especially attractive since the actin-myosin system has no demonstrable resistance to stretch in skeletal muscle. However, one should keep in mind, for example, that in smooth muscle cells there is an intracellular filament system which runs in parallel with the actin-myosin system, the intermediate filament system composed of an entirely different set of proteins, (vimentin, desmin, etc.), whose mechanical properties are essentially unknown. Moreover, as already mentioned, different smooth muscles have different extracellular volumes and different kinds of filaments between the cells. 

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. 

Diseases affecting skeletal muscle are not always primary diseases of muscle, and it is necessary first to determine whether a particular disorder is a primary disease of muscle, is neurogenic in origin, is an inflammatory disorder, or results from vascular insufficiency. A primary disease of muscle is one in which the skeletal muscle fibers are the primary target of the disease. Neurogenic disorders are those in which weakness, atrophy, or abnormal activity arises as a result of pathological processes in the peripheral or central nervous system. Inflammatory disorders may result in T-cell mediated muscle damage and are often associated with viral infections. Vascular insufficiency as a result of occlusion in any part of the muscle vasculature can cause severe disorders of muscle, especially in terms of pain, metabolic insufficiency, and weakness. 

These disorders are all acquired conditions with no evidence of an hereditary basis. Most of them involve inflammation of the skeletal muscle itself (myositis) (Figure 17), though this may sometimes occur because of initial targeting of the muscle vasculature or connective tissue. Many instances of myositis are classed as idiopathic disorders, in that the precise mechanisms of muscle degeneration are not known, but is widely accepted that these syndromes are associated with abnormal function of the immune system. The syndromes of polymyositis (PM) and derma-... 

African trypanosomiasis (sleeping sickness) and American trypanosomiasis (Chagas disease) are caused by Trypanosoma brucei and Trypanosoma cruzi, respectively. Sleeping sickness results from being bitten by the insect vector, the tsetse fly. At first there is only local lymphadenitis but about a month later generalized malaise, fever, and systemic disease involving skeletal muscle is seen. 

Pathogenesis of MH is not completely understood. Skeletal muscle, however, is the one tissue in MH with proven abnormalities, and it is further thought that the basic defect that causes the syndrome lies in the calcium regulation system found within the myoplasm. For example, calcium transport function appears to be decreased in the sarcoplasmic reticulum, mitochondria, and sarcolemma. Thus, the suggestion has been made that MH is characterized by a generalized membrane defeet. 

The somatic motor nervous system or voluntary nervous system consists of nerve libers that irmervate skeletal muscle motor end-plates. 

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... 

Smooth muscles have molecular structures similar to those in striated muscle, but the sarcomeres are not aligned so as to generate the striated appearance. Smooth muscles contain a-actinin and tropomyosin molecules, as do skeletal muscles. They do not have the troponin system, and the fight chains of smooth muscle myosin molecules differ from those of striated muscle myosin. Regulation of smooth muscle contraction is myosin-based, unlike striated muscle, which is actin-based. However, like striated muscle, smooth muscle contraction is regulated by Ca. ... 

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