Muscle contraction mechanism

Examines the muscle-contraction mechanism from a structural perspective. 

In phase 3 of cellular respiration, the high-energy phosphate bonds of ATP are used for processes such as muscle contraction (mechanical work), maintaining low intracellular Na concentrations (transport work), synthesis of larger molecules such as DNA in anabolic pathways (biosynthetic work), or detoxification (biochemical work). As a consequence of these processes, ATP is either directly or indirectly hydrolyzed to ADP and inorganic phosphate (Pi), or to AMP and pyrophosphate (PPi). 

Palladino, J.L. and Noordergraaf, A. 1998. Muscle contraction mechanics from ultrastructural dynamics. In Analysis and Assessment of Cardiovascular Function, G.M. Drzewiecki and J.K.-J. Li, Eds., Springer-Verlag, New York, chap. 3, pp. 53-57. 

The proposed utility of the hexagonal concept of protein conformation in a muscle contraction mechanism has already been noted S. With the large... 

Solutions of F-actin and myosin at high ionic strength = 0.6) in vitro form a complex called actomyosin. The formation of the complex is reflected by an increase in viscosity and occurs in a deflnite molar ratio 1 molecule of myosin per 2 molecules of G-actin, the basic unit of the double-helical F-actin strand. It appears that a spike-like structure is formed, which consists of myosin molecules embedded in a backbone made of the F-actin double helix. Addition of ATP to actomyosin causes a sudden drop in viscosity due to dissociation of the complex. When this addition of ATP is followed by addition of Ca +, the myosin ATPase is activated, ATP is hydrolyzed and the actomyosin complex again restored after the ATP concentration decreases. Upon spinning of an actomyosin solution into water, flbers are obtained which, analogous to muscle flbers, contract in the presence of ATP. Glycerol extraction of muscle fibers removes all the soluble components and abolishes the semipermeability of the membrane. Such a model muscle system shows all the reactions of in vivo muscle contraction after the readdition of ATP and Ca +. This and similar model studies demonstrate that the muscle contraction mechanism is understood in principle, although some molecular details are still not clarified. 

Pig. 2. Proposed mechanism of inbition of smooth muscle contraction by P2" gonists, where AMP is adenosine monophosphate, cAMP is cycHc-3 5 adenosine monophosphate, ATP is adenosine triphosphate, and -P is an attached phosphate. 

Disease States. Rickets is the most common disease associated with vitamin D deficiency. Many other disease states have been shown to be related to vitamin D. These can iavolve a lack of the vitamin, deficient synthesis of the metaboUtes from the vitamin, deficient control mechanisms, or defective organ receptors. The control of calcium and phosphoms is essential ia the maintenance of normal cellular biochemistry, eg, muscle contraction, nerve conduction, and enzyme function. The vitamin D metaboUtes also have a function ia cell proliferation. They iateract with other factors and receptors to regulate gene transcription. 

Soluble Compounds. The mechanism of barium toxicity is related to its ability to substitute for calcium in muscle contraction. Toxicity results from stimulation of smooth muscles of the gastrointestinal tract, the cardiac muscle, and the voluntary muscles, resulting in paralysis (47). Skeletal, arterial, intestinal, and bronchial muscle all seem to be affected by barium. 

In the presence of calcium, the primary contractile protein, myosin, is phosphorylated by the myosin light-chain kinase initiating the subsequent actin-activation of the myosin adenosine triphosphate activity and resulting in muscle contraction. Removal of calcium inactivates the kinase and allows the myosin light chain to dephosphorylate myosin which results in muscle relaxation. Therefore the general biochemical mechanism for the muscle contractile process is dependent on the avaUabUity of a sufficient intraceUular calcium concentration. 

Phosphodiesterase Inhibitors. Because of the complexity of the biochemical processes involved in cardiac muscle contraction, investigators have looked at these pathways for other means of dmg intervention for CHF. One of the areas of investigation involves increased cycHc adenosine monophosphate [60-92-4] (cAMP) through inhibition of phosphodiesterase [9025-82-5] (PDE). This class of compounds includes amrinone, considered beneficial for CHF because of positive inotropic and vasodilator activity. The mechanism of inotropic action involves the inhibition of PDE, which in turn inhibits the intracellular hydrolysis of cAMP (130). In cascade fashion, cAMP-catalyzed phosphorylation of sarcolemmal calcium-channels follows, activating the calcium pump (131). A series of synthetic moieties including the bipyridines, amrinone and milrinone, piroximone and enoximone, [77671-31-9], C22H22N2O2S, all of which have been shown to improve cardiac contractiUty in short-term studies, were developed (132,133). These dmgs... 

Another mechanism in initiating the contraction is agonist-induced contraction. It results from the hydrolysis of membrane phosphatidylinositol and the formation of inositol triphosphate (IP3)- IP3 in turn triggers the release of intracellular calcium from the sarcoplasmic reticulum and the influx of more extracellular calcium. The third mechanism in triggering the smooth muscle contraction is the increase of calcium influx through the receptor-operated channels. The increased cytosolic calcium enhances the binding to the protein, calmodulin [73298-54-1]. 

When exposure is repeated, the allergen binds between two adjacent IgE molecules. This causes release of inflammatory mediators (histamine, leukotrienes, chemotactic factors). These act locally and cause smooth muscle contraction, increased vascular permeability, mucous gland secretion, and infiltration of inflammatory cells (neutrophils and eosinophils). However, histamine can also be released by non-IgE-mediated mechanisms (e.g., due to exposure to certain fungi). 463... 

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.)... 

Excitation-contraction coupling (EC coupling) is the mechanism underlying transformation of the electrical event (action potential) in the sarcolemma into the mechanical event (muscle contraction) which happens all over the muscle. In other words, it is the mechanism governing the way in which the action potential induces the increase in the cytoplasmic Ca2+ which enables the activation of myofibrils. 

Twitch is a muscle contraction caused by a single action potential, whereas tetanus is a sustained muscle contraction caused by a series of repetitive action potentials. The amplitude of tetanus contraction is larger than that of twitch, due to mechanical summation. 

Vasopressin (Rtressin Synthetic) and its derivatives, namely lypressin (Diapid) and desmopressin (DDAVP), regulate the reabsorption of water by the kidneys. Vasopressin is secreted by the pituitary when body fluids must be conserved. An example of this mechanism may be seen when an individual has severe vomiting and diarrhea with little or no fluid intake. When this and similar conditions are present, die posterior pituitary releases the hormone vasopressin, water in die kidneys is reabsorbed into die blood (ie, conserved), and die urine becomes concentrated. Vasopressin exhibits its greatest activity on die renal tubular epithelium, where it promotes water resoqition and smooth muscle contraction throughout die vascular bed. Vasopressin has some vasopressor activity. 

Studies on muscle contraction carried out between 1930 and 1960 heralded the modem era of research on cytoskeletal stmctures. Actin and myosin were identified as the major contractile proteins of muscle, and detailed electron microscopic studies on sarcomeres by H.E. Huxley and associates in the 1950s produced the concept of the sliding filament model, which remains the keystone to an understanding of the molecular mechanisms responsible for cytoskeletal motility. 

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