Skeletal muscle is made up of cells collectively called muscle fibers. Each muscle fiber is multinucleated, with its nuclei located along the periphery of the fiber. Each muscle fiber is further divided into myofibrils, which are the basic units of the muscle fiber. These myofibrils are surrounded by the muscular cell membrane (sarkolemma), which forms deep hollows called transverse tubules (T-tubules) in the myofibril. Each myofibril contains contractile proteins, described as thick, thin filaments, arranged longitudinally in units called sarcomeres. The sliding filament theory describes a process used by muscles for contraction. It is a cycle of repetitive events that cause a thin filament to slide over a thick filament, creating tension in the muscle. It was developed independently in 1954 by Andrew Huxley and Rolf Niedergerke, as well as Hugh Huxley and Jean Hanson.[21] [22] [23] Physiologically, this contraction on the sarcoma is not uniform; The central position of thick filaments becomes unstable and can move during contraction. However, the action of elastic proteins such as titin is believed to maintain a uniform tension on the sarcomere, pulling the thick filament into a central position. [24] Smooth muscle also contains blood pressure-dependent calcium channels and RyRs, which are responsible for increasing intracellular calcium concentration (see below).
Depolarization causes L-type calcium channels to open so that calcium can enter the cell via its concentration gradient (Fig. 1B). The opening of RyRs is usually associated with the ICRC. When the intracellular concentration of calcium increases, calcium binds to RyRs, the resulting opening of which further enhances the increase in cytoplasmic calcium concentration. However, another important mechanism that controls contraction in these cells involves another tetrameric calcium channel with six transmembrane spans: the inositol-1,4,5-trisphosphate receptor (IP3) (IP3R). Circulating hormones (e.B. vasopressin and bradykinin) and neurotransmitters released by sympathetic nerves (e.B. endothelin and norepinephrine) act via G protein-coupled receptors (GPCRs) to produce the second IP3 messenger via phospholipase C (PLC) activation. IP3 binds and opens the IP3R on the ER/SR, causing the release of calcium which causes contraction.
IP3Rs are present in skeletal and cardiac muscles; however, they do not contribute significantly to the excitation-contraction coupling in the striated muscle. It should be noted that RyRs and IP3Rs are stimulated by low concentrations of cytoplasmic calcium, but are close to a higher concentration and have bell-shaped response curves (Bezprozvanny et al., 1991; Finch et al., 1991). Smooth muscles can be divided into two subgroups: one unit and several units. Individual smooth muscle cells can be found in the intestines and blood vessels. Since these cells are connected to each other by lacunar junctions, they can contract as functional syncytium. Individual smooth muscle cells contract myogenically, which can be modulated by the autonomic nervous system. Eccentric contractions usually occur as a braking force as opposed to a concentric contraction to protect the joints from damage. During virtually all routine movements, eccentric contractions help keep movements smooth, but can also slow down quick movements such as a punch or throw. Part of training for fast movements, such as nodding during baseball, is to reduce eccentric brakes so that greater strength can be developed throughout the movement.
Depolarization conduction and Ca2+ release processes occur in the excitation-contraction coupling of skeletal and cardiac muscle (E-C). Although the proteins involved are similar, they differ in structure and regulation. Dihydropyridine receptors (DHPR) are encoded by different genes, and ryanodine receptors (RyRs) are different isoforms. In addition, DHPR comes into contact with RyR1 (the main isoform of RyR in skeletal muscle) to regulate the release of Ca2+ in skeletal muscle, while the L-type calcium channel (DHPR on cardiac myocytes) and RyR2 (the main RyR isoform in the heart muscle) are not physically coupled in the heart muscle, but are faced with a junctional coupling. [32] The main pathways that promote muscle relaxation are the second messenger substances cAMP and cyclic guanosine monophosphate (cGMP). cAMP is produced by adenylylcyclases downstream of the coupled GS receptor β-adrenergic receptor activated by norepinephrine. Note that the cAMP signaling pathway generally promotes contraction in the heart muscle; However, in smooth muscle, activation of cAMP causes relaxation. The cGMP signaling pathway can be activated by nitric oxide (NO) or natriuretic peptides (NP). In the case of blood vessels and other smooth muscles, the NO produced by endothelial NO synthase (eNOS) diffuses through the muscle cell membrane to activate soluble guanylyl cyclase (sGC), which increases cGMP levels. NPs, such as the little finger (ANP, released by cardiac atria under high blood pressure), the brain (BNP, mainly released by the ventricle) and type C (CNP, mainly involved in pathological conditions and released by the vascular and central nervous systems), bind instead to transmembrane guanylyl cyclase, whose intracellular domain has enzymatic activity (Nishikimi et al. 2011). The cAMP and cGMP generated act on the contractile process via the protein kinase PKA and PKG in several ways: (1) their phosphorylation of calcium pumps leads to increased activity; (2) Activation of MLC phosphatase (MLCP) by PKG-antagonized mlCK; and (3) PKA and PKG result in reduced sensitivity of contractile machinery by inhibiting RHOA GTPase (which increases MLCP activity and causes MLC dephosphorylation and muscle relaxation).
CAMP and cGMP levels are in turn regulated by their degradation by phosphodiesterases to obtain the inactive metabolites 5′-AMP and 5′-GMP. Myasthenia gravis is an autoimmune disease that affects the neuromuscular connection. It is characterized by tired skeletal muscle weakness, which worsens with repetitive movements and improves with rest. Most often, myasthenia gravis initially involves weakness of the eye muscles with possible progression to the muscles of the limbs. Most patients with this disease have autoantibodies against the nicotinic ACh receptors of the neuromuscular compound, which causes endocytosis and receptor degradation. Without ACh binding to receptors, action potentials cannot spread through the muscle fiber and, as a result, muscle weakness occurs. Acetylcholinesterase inhibitors prevent the breakdown of ACh and are used to increase neuromuscular transmission for the treatment of myasthenia gravis. [9] (2) Chemical reactions cause the reorganization of muscle fibers in such a way that the muscle is shortened – this is contraction. Because DMD is caused by a mutation in the gene that codes for dystrophin, it was thought that introducing healthy myoblasts into patients could be an effective treatment. Myoblasts are the embryonic cells responsible for muscle development and, ideally, they would carry healthy genes that could produce the dystrophin needed for normal muscle contraction. This approach has been largely unsuccessful in humans.
A new approach was to try to stimulate muscle production of utrophin, a dystrophin-like protein that might be able to play the role of dystrophin and prevent cell damage. Let`s take a closer look at the stages of the mechanism of muscle contraction. Overview of muscle contraction signals in striated (A) and smooth (B) muscles. The process of muscle contraction occurs through a number of key stages, including: with eccentric contraction, the isometrically generated tension is not enough to overcome the external load on the muscle, and the muscle fibers lengthen as they contract. [9] Instead of working to pull a joint towards muscle contraction, the muscle acts to slow down the joint at the end of a movement or otherwise control the repositioning of a load. This may be unintentional (for example. B, when you try to move a weight that is too heavy for the muscle to lift) or voluntarily (for example. B when the muscle “smoothes” a movement or resists gravity, by.
B example when you walk downhill). In the short term, strength training, which involves both eccentric and concentric contractions, seems to increase muscle strength more than training with concentric contractions alone. [10] However, exercise-induced muscle damage is also greater during prolonged contractions. [11] The movements of myosin seem to be a kind of molecular dance. .
