Muscle contraction association

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. 

Calcium and Vascular Smooth Muscle Contraction. Calcium acts on a number of sites associated with the control of the cytoplasmic calcium concentration. Vascular smooth muscle contraction can be initiated by the opening of the slow calcium channel aUowing influx of extraceUular calcium through the sarcolemmal membrane into the cytoplasmic compartment. The iatraceUnlar calcium concentration increases to 1 x 10 Af, a threshold concentration necessary to initiate contraction. 

In addition to the major proteins of striated muscle (myosin, actin, tropomyosin, and the troponins), numerous other proteins play important roles in the maintenance of muscle structure and the regulation of muscle contraction. Myosin and actin together account for 65% of the total muscle protein, and tropomyosin and the troponins each contribute an additional 5% (Table 17.1). The other regulatory and structural proteins thus comprise approximately 25% of the myofibrillar protein. The regulatory proteins can be classified as either myosin-associated proteins or actin-associated proteins. 

However, release of ADP and P from myosin is much slower. Actin activates myosin ATPase activity by stimulating the release of P and then ADP. Product release is followed by the binding of a new ATP to the actomyosin complex, which causes actomyosin to dissociate into free actin and myosin. The cycle of ATP hydrolysis then repeats, as shown in Figure 17.23a. The crucial point of this model is that ATP hydrolysis and the association and dissociation of actin and myosin are coupled. It is this coupling that enables ATP hydrolysis to power muscle contraction. 

Botulinum neurotoxins are widely used as therapeutic agents to cause reduction or paralysis of skeletal muscle contraction. They are used to treat cervical dystonia, which causes regional involuntary muscle spasms often associated with pain. Moreover, they are used in strabism, blepharospasm, hemifacial spasm, and... 

Troponin is a regulator of striated muscle contraction. Measurements of troponin I levels are routinely used in the diagnosis of myocardial infarction. In addition, mutations in the troponin I subunit are associated with familial hypertrophic cardiomyopathy. 

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. 

Muscle contraction is initiated by a signal from a motor nerve. This triggers an action potential, which is propagated along the muscle plasma membrane to the T-tubule system and the sarcotubular reticulum, where a sudden large electrically excited release of Ca " into the cytosol occurs. Accessory proteins closely associated with actin (troponins T, I, and C) together with tropomyosin mediate the Ca -dependent motor command within the sarcomere. Other accessory proteins (titin, nebulin, myomesin, etc.) serve to provide the myofibril with both stability... 

Since Ca is transferred from one side of the membrane to the other side in association with the Ca -ATPase, thermal fluctuation of critical regions of the Ca -ATPase influenced in specific ways through the phosphorylation of the enzyme by ATP may play a role in Ca translocation. Similar ideas have been proposed some time ago by Huxley [419] in relationship to crossbridge movements during muscle contraction and by Welch and others on the role of protein fluctuations in enzyme action [420-430]. 

Physical restraints (may be associated with isometric muscle contractions and worsening of hyperthermia)... 

Phenothiazines may cause sedation, orthostatic hypotension, and extrapyramidal symptoms (EPS) such as dystonia (involuntary muscle contractions), tardive dyskinesia (irreversible and permanent involuntary movements), and akathisia (motor restlessness or anxiety).1,21,22 Chronic phenothiazine use has been associated with EPS, but single doses have also caused these effects.23... 

Dystonia A type of dyskinesia. The movement is slow and twisting. It may be associated with painful muscle contractions or spasms. 

Baroreceptors are sensitive to changes in MAP. As VR, CO, and MAP decrease, baroreceptor excitation is diminished. Consequently, the frequency of nerve impulses transmitted from these receptors to the vasomotor center in the brainstem is reduced. This elicits a reflex that will increase HR, increase contractility of the heart, and cause vasoconstriction of arterioles and veins. The increase in CO and TPR effectively increases MAP and therefore cerebral blood flow. Constriction of the veins assists in forcing blood toward the heart and enhances venous return. Skeletal muscle activity associated with simply walking decreases venous pressure in the lower extremities significantly. Contraction of the skeletal muscles in the legs compresses the veins and blood is forced toward the heart. 

Arteriolar resistance changes that take place in order to maintain a constant blood flow are explained by the myogenic mechanism. According to this mechanism, vascular smooth muscle contracts in response to stretch. For example, consider a situation in which blood pressure is increased. The increase in pressure causes an initial increase in blood flow to the tissue. However, the increased blood flow is associated with increased stretch of the vessel wall, which leads to the opening of stretch-activated calcium channels in the vascular smooth muscle. The ensuing increase in intracellular calcium results in vasoconstriction and a decrease in blood flow to the tissue toward normal. 

Dystonia is characterized by sustained muscle contractions. In patients with dystonia, normal movements are disrupted by cocontraction of agonist and antagonist muscles, and by excessive activation of inappropriate musculature (overflow), leading to abnormal postures and slow involuntary twisting movements, which are often associated with movement execution. 

In addition to the displacement of caldesmon, smooth muscle cell contraction requires kinase-induced phosphorylation of myosin. Smooth muscle has a unique type of myosin filament called p-light chains which are the target (substrate) for MLCK, but MLCK is only active when complexed with CaCM. Myosin light chain phosphatase reverses the PKA-mediated process and when cytosolic calcium ion concentration falls, CDM is released from CaCM and re-associates with the actin. The central role of calcium-calmodulin in smooth muscle contraction is shown in Figure 7.4. 

Movement. The interaction between actin and myosin is responsible for muscle contraction and cell movement (see p.332). Myosin (right), with a length of over 150 nm, is among the largest proteins there are. Actin filaments (F-actin) arise due to the polymerization of relatively small protein subunits (G-actin). Along with other proteins, tropomyosin, which is associated with F-actin, controls contraction. 

Microfilaments of F actin traverse the microvilli in ordered bundles. The microfila-ments are attached to each other by actin-as-sociated proteins, particularly fimbrin and vil-lin. Calmodulin and a myosin-like ATPase connect the microfilaments laterally to the plasma membrane. Fodrin, another microfila-ment-associated protein, anchors the actin fibers to each other at the base, as well as attaching them to the cytoplasmic membrane and to a network of intermediate filaments. In this example, the microfilaments have a mainly static function. In other cases, actin is also involved in dynamic processes. These include muscle contraction (see p. 332), cell movement, phagocytosis by immune cells, the formation of microspikes and lamellipo-dia (cellular extensions), and the acrosomal process during the fusion of sperm with the egg cell. 

Muscle contraction is associated with a high level of ATP consumption (see p. 332). Without constant resynthesis, the amount of ATP available in the resting state would be used up in less than 1 s of contraction. 

Leukotrienes are products of arachidonic acid metabolism and are released from mast cells and eosinophils. Leukotrienes and leukotriene receptor occupation have been correlated with airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. 

Many of the biochemical and molecular events that are responsible for uterine smooth muscle contraction are the same as those that control other smooth muscle tissues (Fig. 62.1). Once uterine smooth muscle sensitivity has been augmented, actin and myosin must interact for contraction to occur. This interaction depends on the phosphorylation of the contractile proteins by the enzyme myosin light chain kinase (MLCK). This enzyme requires Ca++ and is active only when associated with calmodulin. Activation of the entire muscle contraction... 

Mecfianism of Action A skeletal muscle relaxant that reduces muscle contraction by interfering with release of calcium ion. Reduces calcium ion concenfrafion. Therapeutic Effect Dissociafes excitation-conf racf ion coupling. Interferes wifh catabolic process associated with malignant hyperthermic crisis. 

Unlabeled Uses Muscle contraction, headache, external sphincter spasticity, muscle rigidity, opisthotonos-associated with tetanus... 

Histamine is an amine found in the cells of all animals (Figure 15.20). The release of histamine in the body is associated with involuntary muscle contraction and dilation of the blood vessels. Allergic reactions release histamine in the body and produce the accompanying side effects associated with hay fever such as coughing, sneezing, and ruimy nose. These effects can be alleviated with the use of antihistamines. 

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