Skeletal muscle mechanisms

One possible mechanism responsible for the abiHty of trenbolone acetate to stimulate skeletal muscle hypertrophy may be through enhanced proliferation and differentiation of satelHte ceUs as the result of increased sensitivity to insuHn-Hke growth factor-I (IGE-1) and fibroblast growth factor (43). 

Mechanism of Action. P-Agonists stimulate skeletal muscle growth by accelerating rates of fiber hypertrophy and protein synthesis, but generally do not alter muscle DNA content in parallel with the increases in protein accretion (133—135). This is in contrast to the effects of anaboHc steroids and ST on skeletal muscle growth. Both of the latter stimulate fiber hypertrophy and muscle protein synthesis, but also increase muscle DNA content coincident with increased protein accretion. Whether the P-agonists decrease muscle protein degradation is equivocal. 

FIGURE 17.23 The mechanism of skeletal muscle contraction. The free energy of ATP hydrolysis drives a conformational change in the myosin head, resulting in net movement of the myosin heads along the actin filament. Inset) A ribbon and space-filling representation of the actin—myosin interaction. (SI myosin image courtesy of Ivan Rayment and Hazel M. Holden, University of Wiseonsin, Madison.)... 

In higher animals, large percentages of the terminal cisternae of cardiac muscle are not associated with t-tubules at all. For SR of this type, Ca release must occur by a different mechanism from that found in skeletal muscle. In this case, it appears that Ca leaking through sarcolemmal Ca channels can trigger the release of even more Ca from the SR. This latter process is called Ca -induced Ca release (abbreviated CICR). 

Metformin restrains hepatic glucose production principally by suppression of gluconeogenesis. The mechanisms involve potentiation of insulin action and decreased hepatic extraction of certain gluconeogenic substrates such as lactate. In addition, metformin reduces the rate of hepatic glycogenolysis and decreases the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake and glycogenesis by skeletal muscle is increased by metformin mainly by increased... 

Uptake of LCFAs across the lipid-bilayer of most mammalian cells occurs through both a passive diffusion of LCFAs and a protein-mediated LCFA uptake mechanism. At physiological LCFA concentrations (7.5 nM) the protein-mediated, saturable, substrate-specific, and hormonally regulated mechanism of fatty acids accounts for the majority (>90%) of fatty acid uptake by tissues with high LCFA metabolism and storage such as skeletal muscle, adipose tissue, liver,... 

The exact mechanism by which PPARy ligands affect insulin resistance (improved glucose uptake by peripheral tissues, most notably skeletal muscle) remains unclear. 

The RyR channels seem to be regulated by luminal Ca2+. Luminal Ca2+ may activate theRyR2 channels in the heart. The association of calsequestrin with RyR2 via triadin or junctin is proposed as a possible regulatory mechanism. Such activation by luminal Ca2+ remains controversial in the skeletal muscle. 

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. 

The smooth muscle cell does not respond in an all-or-none manner, but instead its contractile state is a variable compromise between diverse regulatory influences. While a vertebrate skeletal muscle fiber is at complete rest unless activated by a motor nerve, regulation of the contractile activity of a smooth muscle cell is more complex. First, the smooth muscle cell typically receives input from many different kinds of nerve fibers. The various cell membrane receptors in turn activate different intracellular signal-transduction pathways which may affect (a) membrane channels, and hence, electrical activity (b) calcium storage or release or (c) the proteins of the contractile machinery. While each have their own biochemically specific ways, the actual mechanisms are for the most part known only in outline. 

Westerblad, H., Lee, J.A., Lannergren, J., Allen, D.G. (1991). Cellular mechanisms of fatigue in skeletal muscle. Am. J. Physiol. 261, CI95-C209. 

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-... 

Thus, Ca " controls skeletal muscle contraction and relaxation by an allosteric mechanism mediated by TpC, Tpl, TpT, tropomyosin, and F-actin. 

In summary, therefore, the evidence seems convincing that exercise modifies circulating and tissue concentrations of antioxidants and enzyme activities. It is much less certain that the fatigue or damage to skeletal muscle associated with various forms of excessive or unaccustomed exercise is initiated by free radical-mediated degradation. Considerably more work is required in this area to clarify the underlying pathogenic mechanisms. 

Marwah, J. El ectrophysiological studies of ketamine action in frog skeletal muscle. Neuropharmacoloqy 19 765-772, 1980. Marwah, J. Candidate mechanisms underlying phencyclidine-induced psychosis An electrophysiologica 1, behavioral and biochemical... 

FIGURE 57-1. Skeletal muscle fiber organization. Tendons attach muscle to bone. (From Widmaier EP, Raff H, Strang KT, et al, (eds.) Vander, Sherman, Luciano s Human Physiology The Mechanisms of Body Function. 9th ed. New York McGraw-Hill 2004, Figure 9-1.)... 

Paralysis usually is reserved for cases in whom sedation alone does not improve the effectiveness of mechanical ventilation. Neuromuscular blockers may lead to prolonged skeletal muscle weakness and should be avoided if possible. Patients requiring neuromuscular blockade are to be monitored and intermittent boluses should be utilized. 

Three major mechanisms of action have dominated as possible explanations for the ergogenic potential of caffeine in the enhancement of exercise performance. These three mechanisms involve (1) the mobilization of intracellular calcium from the sarcoplasmic reticulum of skeletal muscle, (2) the increase of cyclic-3 ,5 -adenosine monophosphate (cAMP) by the inhibition of phosphodiesterases in muscles and adipocytes, and (3) the competitive antagonism of adenosine receptors, primarily in the central nervous system (CNS).8 9... 

Lingle, C. L., Maconochie, D., and Steinbach, J. H., Activation of skeletal muscle nicotinic acetylcholine receptors, J. Memb. Biol., 126, 195-217, 1992 (excellent review of much of the evidence concerning the mechanism of receptor activation). 

This section will examine the mechanism of simple or basic spinal reflexes that control skeletal muscles. 

The mechanism of skeletal muscle contraction is described by the Sliding Filament Theory (see Figure 11.2). This mechanism begins with the "priming ... 

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