Muscle fiber mechanisms

A skinned fiber is a muscle fiber, the sarcolemma of which has been mechanically removed or which is made freely permeable to small molecules, such as Ca2+, Mg2+, EGTA, ATP, soluble enzymes and others by a chemical agent (saponin, (3-escin or Staphylococcus a-toxin). The organization of the sarcoplasmic reticulum (SR) and myofibrils is kqrt as they are in the living muscle. 

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. 

However, by carrying out experiments with skinned fibers, the composition of the solution surrounding the myofibrils can be controlled and the mechanical properties of the muscle fiber can be related more easily to the biochemistry of force... 

Both mechanics and biochemical studies of muscle fibers suggest there is more than one force generating state. Crossbridges are thought to attach initially as... 

The high active tension and/or high active strain that occurs in muscle during lengthening contractions is believed to cause mechanical disruption of muscle fibers and connective tissue (Armstrong, 1984 Lieber and Friden, 1993). Activa-... 

The histopathological features of PM may be radically different from those of JDM and ADM. There is little, if any, evidence of involvement of the micro vasculature and the muscle necrosis which occurs appears to be the direct result of targeting of individual muscle fibers. In the dermatomyositis syndromes, antibody-dependent humoral mechanisms are predominant and B-lymphocytes are seen to be the most abundant cell type in almost all JDM cases and a substantial proportion of ADM cases. In contrast, most muscle biopsies from PM patients show evidence of inflammation in which TS (cytotoxic) lymphocytes predominate (Figure 20). Moreover, the distribution of inflammatory cell infiltrates tends to be different. Instead of the mainly perifascicular location of lymphocytes in JDM/ADM, there... 

Two major types of muscle fibers are found in humans white (anaerobic) and red (aerobic). The former are particularly used in sprints and the latter in prolonged aerobic exercise. During a sprint, muscle uses creatine phosphate and glycolysis as energy sources in the marathon, oxidation of fatty acids is of major importance during the later phases. Nonmuscle cells perform various types of mechanical work carried out by the structures constituting the cytoskeleton. These strucmres include actin filaments (microfilaments), micrombules (composed primarily of a- mbulin and p-mbulin), and intermediate filaments. The latter include keratins, vimentin-like proteins, neurofilaments, and lamins. 

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.)... 

The amount of tension developed by a muscle fiber during tetanic contraction can be as much as three to four times greater than that of a single muscle twitch. The mechanism involved with this increased strength of contraction involves the concentration of cytosolic calcium. Each time muscle fiber is stimulated by an action potential, Ca++ ions are released from the sarcoplasmic reticulum. However, as soon as the these ions are released, a... 

The skeletal muscle relaxant that acts directly on the contractile mechanism of the muscle fibers is... 

Fujino, M., T. Arima, Y. Sato, and H. Tako. 1985. Suppression of action of some excitation-contraction (E-C) uncoupling agents and mechanism in E-C coupling in single skeletal muscle fibers of frog, R. japonica. Jour. Physiol. Soc. Japan 47 519. 

Muscle contraction is triggered by motor neurons that release the neurotransmitter acetylcholine (see p. 352). The transmitter diffuses through the narrow synaptic cleft and binds to nicotinic acetylcholine receptors on the plasma membrane of the muscle cell (the sarcolemma), thereby opening the ion channels integrated into the receptors (see p. 222). This leads to an inflow of Na which triggers an action potential (see p. 350) in the sarcolemma. The action potential propagates from the end plate in all directions and constantly stimulates the muscle fiber. With a delay of a few milliseconds, the contractile mechanism responds to this by contracting the muscle fiber. 

Dantrolene is a drug that causes spastic muscle contraction. Unlike other muscle relaxants, it has a direct effect on the contractile mechanism by interfering in the process of calcium ion release from the sarcoplasmic reticulum. This results in a lack of coordination in the mechanism of excitation—contraction of skeletal muscle, which has a greater effect on fast muscle fibers than on slow muscle fibers. Dantrolene is used for controlling the onset of clinical spasticity resulting from serious clinical cases such as wounds, paralysis, cerebral palsy, and disseminated sclerosis. Synonyms of this drug are dantrium and danlen. 

Mechanism of Action A cardiac inotropic agent that increases the influx of calcium from extracellular to intracellular cytoplasm. Therapeutic Effect Potentiates the activity of the contractile cardiac muscle fibers and increases the force of myocardial contraction. Slows the heart rate by decreasing conduction through the SA and AV nodes. Pharmacokinetics ... 

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). 

The enlargement of individual muscle cells and muscle fibers via elevated protein synthesis caused by anabolic substances. This is the first growth mechanism and its called hypertrophy. Androgens such as testosterone (endogenous or exogenous) and all AAS have the greatest effect at this level. 

Reduced salt intake also negatively effects the all important sodium-potassium pump. This is the mechanism the body uses to shuttle many nutrients into cells like those that all muscle fibers are composed of. (Gee, ya think ) This would therefore inhibit creatine and some amino acid structures from adequately transporting, as well as inhibit glycogen synthesis. 

The mechanism by which electroporation enhances i.m. pDNA expression and efficacy requires further study. For muscle transfection, it has been demonstrated that electroporation appears to increase the number of muscle fibers transfected by as much as ten-fold (Dupuis et al., 2000). In addition, the number of muscle nuclei containing transfected pDNA is higher after electroporation. The mechanism by which electroporation enhances transfection of tumor tissue is unclear at this time. 

Bershitsky, S., Tsaturyan, A., Bershitskaya, O., Mashanov, G., Brown, P., Webb, M., and Ferenczi, M. A. (1996). Mechanical and structural properties underlying contraction of skeletal muscle fibers after partial l-ethyl-3-[3-dimethylamino)propyl]carbodii-mide cross-linking. Biophys.J. 71, 1462-1474. 

Dantrolene is a hydantoin derivative related to phenytoin that has a unique mechanism of spasmolytic activity. In contrast to the centrally active drugs, dantrolene reduces skeletal muscle strength by interfering with excitation-contraction coupling in the muscle fibers. The normal contractile response involves release of calcium from its stores in the sarcoplasmic reticulum (see Figures 13-1 and 27-10). This activator calcium brings about the tension-generating interaction of actin with myosin. Calcium is released from the sarcoplasmic reticulum via a calcium channel, sometimes called the ryanodine receptor channel because the plant alkaloid ryanodine combines with a receptor on the channel protein and, in the case of the skeletal muscle channel, locks it in the open position. 

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