Skeletal muscle contractile activity

The compliance in series with the active force. Force exerted by the activated elements must be transmitted or borne by whatever structural elements are in series with them. In skeletal muscle there is clearly a tendon in series but not so with smooth muscle. In smooth muscle, the total length of contractile apparatus is broken up into individual cells with intercalating extracellular connective structures. In addition, the portions of the crossbridges in series with the pulling site must also be stretched before force can rise to isometric levels. Taken together, the... 

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. 

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... 

McArdle, A., Edwards, R.H.T. and Jackson, M.J. (1993). Calcium homeostasis during contractile activity of vitamin E deficient skeletal muscle. Proc. Nutr. Soc. 52, 83A. 

Many factors influence the contractile activity of smooth muscle. The strength of contraction of multiunit smooth muscle may be enhanced by stimulation of a greater number of cells, or contractile units. This mechanism is directly comparable to motor-unit recruitment employed by skeletal muscle. As the number of contracting muscle cells increases, so does the strength of contraction. However, this mechanism is of no value in single-unit smooth muscle. Due to the presence of gap junctions, all of the muscle cells in the tissue are activated at once. 

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. 

In both cases, there is a need for vigorous activity of skeletal musculature. To ensure adequate supply of oxygen and nutrients, blood flow in skeletal muscle is increased cardiac rate and contractility are enhanced, resulting in a larger blood volume being pumped into the circulation. Narrowing of splanchnic blood vessels diverts blood into vascular beds in muscle. 

Smooth muscle effects. The opposing effects on smooth muscle (A) of a-and p-adrenoceptor activation are due to differences in signal transduction (p. 66). This is exemplified by vascular smooth muscle (A). ai-Receptor stimulation leads to intracellular release of Ca + via activation of the inositol tris-phosphate (IP3) pathway. In concert with the protein calmodulin, Ca + can activate myosin kinase, leading to a rise in tonus via phosphorylation of the contractile protein myosin. cAMP inhibits activation of myosin kinase. Via the former effector pathway, stimulation of a-receptors results in vasoconstriction via the latter, P2-receptors mediate vasodilation, particularly in skeletal muscle - an effect that has little therapeutic use. 

Smooth muscle differs from skeletal muscle in various ways. Smooth muscles—which are found, for example, in blood vessel walls and in the walls of the intestines—do not contain any muscle fibers. In smooth-muscle cells, which are usually spindle-shaped, the contractile proteins are arranged in a less regular pattern than in striated muscle. Contraction in this type of muscle is usually not stimulated by nerve impulses, but occurs in a largely spontaneous way. Ca (in the form of Ca -calmodulin see p.386) also activates contraction in smooth muscle in this case, however, it does not affect troponin, but activates a protein kinase that phosphorylates the light chains in myosin and thereby increases myosin s ATPase activity. Hormones such as epinephrine and angiotensin II (see p. 330) are able to influence vascular tonicity in this way, for example. 

The major allergen of molluscan shellfish is tropomyosin, a muscle protein. The term major allergen is used to define proteins that elicit IgE binding in the sera of half or more of patienfs wifh allergies to the specific source (Metcalfe et ah, 1996). Tropomyosin is a ubiquitous muscle protein in all animals. Tropomyosin is a 34- to 36-kDa protein that is highly water soluble and heat stable as evidenced by the fact that tropomyosin can be isolated from fhe water used to boil shrimp (Daul et ah, 1994). Tropomyosin can actually be found in bofh muscle and many nonmuscle cells in animals. In muscle cells, tropomyosin is associated with the thin filaments in muscle and plays a role in the contractile activity of muscle cells. In nonmuscle cells, tropomyosin is found in microfilaments but its fimction is less well imderstood. Tropomyosins are present in all eukaryotic cells. Different isoforms of tropomyosin are found in different types of muscle cells (skeletal, cardiac, smooth), brain, fibroblasts, and other nonmuscle cells. While these tropomyosins are highly homologous, small differences do exist in their... 

Beside this there are some major differences with the neurotransmission in the autonomous nervous system The contractile activity of the skeletal muscle is almost completely dependent on the innervation. There is no basal tone and a loss of the innervation is identical to a total loss in function of the particular skeletal muscle. In contrast to the target organs of the parasympathetic nervous system the skeletal muscle cells only have acetylcholine receptors at the site of the so-called end-plate, the connection between neuron and muscle cell with the rest of the cell surface being insensitive to the transmitter. The release of acetylcholine results in a postjunctional depolarization which is either above the threshold to induce an action potential and a contraction or below the threshold with no contractile response at all. In contrast to the graduated reactions of the parasympathetic target organs, this is an all or nothing transmission. 

Activation of aj-adrenoceptors in smooth muscle of blood vessels leads to vasoconstriction, while activation of Pj-adrenoceptors in blood vessels of skeletal muscle produces vasodilation. Activation of Pi-adrenoceptors on cardiac tissue produces an increase in the heart rate and contractile force. 

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. 

Williams, R.S., and P.D. Neufer (1996). Regulation of gene expression in skeletal muscle by contractile activity. Handbook of Physiology, Section 12 1124-1150. 

Calcium is known to be an important key regulator for contractile activities of both skeletal and smooth muscles. There are two general mechanisms of regulation of muscle contraction actin based and myosin based. 

The majority of insect neuropeptides discovered thus far seem to have the property of regulating the contractile activity of either skeletal and/or visceral muscles. Whether these are the principal or auxiliary modes of action for a given peptide must await a more comprehensive assessment of their individual profiles of activity in a variety of physiological systems. What follows is a summary of our current understanding of the physiological and pharmacological properties of the insect neuropeptides that regulate muscle activity. 

Rarely, on injecting suxamethonium, contracture, instead of the usual relaxation, of skeletal muscles ensues. In denervated muscles the postulated mechanism is direct activation of the contractile mechanism by suxamethonium because of the widespread chemosensitivity of the muscle fiber membranes. 

Anabolic steroids decrease catabolism and increase skeletal muscle protein synthesis. Whether this results in muscular hypertrophy or hyperplasia, or a combination of these, is unclear and probably depends upon the muscle studied. Different muscle types contain different cytosolic receptor numbers and, therefore, the response to anabolic steroids varies. Anabolic steroids initiate an increase in RNA polymerase activity and the synthesis of either structural or contractile proteins. In some muscles, anabolic steroids may increase the ratio of fast twitch to slow twitch fibers (Nimmo et al 1982, Snow et al 1982). Increased activity of enzymes involved in energy metabolism may also occur. However, the total glycogen content may remain unchanged (Hyyppa et al 1997). The effects are most profound in females and castrated males (Snow 1993). 

The contractile activity of all types of muscle (smooth, skeletal) is regulated primarily by the reversible phosphorylation of myosin. Myosin of smtxtth muscle consists of two heavy chains (MW 2(X).000 each) that arc coiled to produce a filamentous tail. Each heavy chain is asstK ialcd with two pairs of light chains (MW 20,0(K) and 16,(XX)) that serve as substrates for calcium- and calmodulin-dependent protein ki-na.ses in the contraction procc.ss. Together with actin (MW 43,000) they participate in a cascade of biiK hemical events that are part of the processes of muscle contraction and relaxation (Fig. 19-2). 

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