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Morphological and functional differences in muscle and muscle fibers (especially in frogs and rabbits) have been known for a long time (170, 412, 481). However, systematic fiber typing did not begin until the 1950s, after Krã1/4ger distinguished between “fibril structure” fibers (uniformly distributed myofibrils) and “field structure” fibers (bundled myofibrils) in several vertebrates (including humans) (273, 274, 276). In the following decades, several classification systems were proposed, which are summarized in Table 1. Overall, the importance of RyR for Ca2+-regulated muscle function can hardly be overstated. On the one hand, this large protein complex provides the entry point to activate the signals that come from the depolarization of the surface membrane and DHPR activation. On the other hand, it releases Ca2+ from SR, a process strictly controlled by the concentration of Ca2+ in the SR, as well as by many other factors that play a regulatory role with mostly unknown molecular mechanisms. The RyR discussed in the previous section plays a crucial role in malignant hyperthermia (HD). HD is known in humans (95, 319) and pigs; It is caused by a pathophysiological reaction of skeletal muscles to certain anesthetics and muscle relaxants. A HD attack is life-threatening and is one of the leading causes of death during general anesthesia in humans. The event was estimated at 1:12,000 to 1:40,000 general anesthesia (351). An attack begins with muscle hypermetabolism, contractures and a subsequent dramatic increase in body temperature [up to 1 ° C per 5 min and up to 43 ° C (hyperthermia) (168)]. Susceptibility to THE DEVELOPMENT OF HD (MHS) during anesthesia is genetic and is transmitted as an autosomal dominant trait. MHS can be tested by exposing biopsied muscle bundles to triggering substances such as caffeine, halogen, succinylcholine, ryanodine (116, 283,513a) or 4-chloro-m-cresol (197).

When the muscle bundles of people with MHS are exposed to any of these drugs, the beams show faster force production or respond to lower drug concentrations than controls. This has led to the development of standardized in vitro contracture tests (283, 513b), which are commonly used to test MHS. Skeletal muscle hypertrophy and switch to glycolytic metabolism of differentiated myotubes induced by growth factors such as insulin-like growth factor or insulin are mediated by Ca2+/CaM-dependent calcineurin (468). During muscle hypertrophy, calcineurin induces the expression of transcription factor GATA-2, which is associated with calcineurin and a specific isoform of transcription factor NFATc1 (366). Cyclosporine prevents muscle hypertrophy and muscle fiber conversion associated with functional overload in vivo, suggesting that postoperative muscle atrophy and weakness are due to administration of the immunosuppressant cyclosporine (111). Calcineurin activity has been shown to selectively upregulate fiber-specific slow gene promoters, and inhibition of calcineurin results in slow to rapid fiber transformation (66). Transcriptional activation of slow-type genes is mediated by the transcription factors NFAT and MEF2. Based on these results, it was speculated that calcineurin could become clinically relevant, as altering its activity could be used to quickly convert into slow muscles, the latter being less affected by dystrophy. This is a good example of how the Ca2+ signaling system can directly specify the gene expression specific to the fiber type and thus determine the phenotype of a muscle fiber. In summary, HD is a disorder of ca2 + release of skeletal muscles with the phenotype of increased sensitivity of the muscle to certain triggering substances used during anesthesia. The discovery that MHS may be caused by mutations in the L-type muscle RyR1 and Ca2+ channels indicates the set of associated proteins that make up the t-tubular/SR compound (Figs. 4 and 6).

The structural integrity and function of this complex appears to be very important for the normal process of muscle activation. Clarifying the genetic and physiological basis of MHS loci 2, 3, 4 and 6 will lead to major advances in understanding the Ca2+ control of skeletal muscle. The fact that myoplasmic Ca2+ levels can get out of control as a result of changes in RyR function underscores the importance of this calcium cycle component. The molecular mechanism by which myosin and acting myofilaments slide over each other is called the transverse bridge cycle. During muscle contraction, the heads of the myosin myofilaments quickly bind and detach and detach in a rattling manner, dragging along the myofilament actin. The amount of force and movement generated by a single sarcomere is small. However, multiplied by the number of sarcomeres in a myofibril, myofibrils in a myocyte and myocytes in a muscle, the amount of force and movement generated is significant. Each myocyte contains several nuclei due to its derivation from multiple myoblasts, progenitor cells from which myocytes originate. These myoblasts are located on the periphery of the myocyte and are flattened so as not to affect the contraction of the myocytes. • Calcium ions and the tropomyosin and troponin proteins control muscle contractions If we return to the pathophysiology of the dystrophinicate muscle, the calcium hypothesis mentioned above and the leaking membrane hypothesis can be integrated into a soulchanical hypothesis.â A higher fragility of the plasma membrane during mechanical activity seems to be the direct physiological consequence of a dystrophin deficiency.

This increased fragility leads to short-lived membrane lesions of limited size, which allow cytoplasmic molecules to flow from the cell and the influx of molecules into the sarcoplasm. The outflow of cytoplasmic components is probably an indicator of damage to the muscle membrane rather than of great pathophysiological importance. Among the molecules that enter muscle fibers, Ca2+ is thought to have the greatest pathogenic consequences (155). An increased influx of Ca2+ into the sub-sarcoemic space can lead to activation of degrading enzymes and overload and dysfunction of the ca2+ cycle and storage systems. This leads to damage to the sarcolemma from within, impaired mitochondrial function and modulation of intracellular signaling pathways (Figs. 13 and 14). Pv is a high-affinity Ca2+ binding protein found at high concentrations in the rapidly contraction/relaxation skeletal muscle fibers of vertebrates (examined in refs. 26, 27, 390). In rats and mice, type IIB fibers show the highest immune reactivity for PV with varying degrees of intensity (Fig. 2). The majority of type IIA fibers (60-70%) have a moderate (also graduated) coloring intensity. Other Type IIA and Type I fibres lack PV (65,144, 190, 363).

The different muscle fibers of the rabbit have a very similar distribution of PV (292, 456). In human muscles, PV is detectable only in intrafusal fibers (137). Primary defects in myotonia and periodic paralysis are due to mutations in genes that code for voltage-dependent ion channels. Increased membrane excitation causes several secondary changes, including fiber-like transformations. Mouse animal models of myotonia will be particularly useful for elucidating the relationships between membrane excitation, muscle activity and gene transcription. Changes in Ca2+/CaM-dependent cell signaling are likely involved in the secondary changes observed in the myotonic muscle. Sarcoma and sliding filament contraction patterns: During contraction, myosin ratchets are tightened along the actin myofilaments that compress the I and H bands. During stretching, this tension relaxes and the I and H bands expand. The A-band remains constant throughout, as the length of myosin myofilaments does not change. The process of muscle contraction occurs through a number of key stages, including: Several recent journals and book articles deal with various aspects of muscle plasticity and the individual components of the Ca2+ cycle device.

The reader is referred to only one article on each subtopic, which should contain enough citations for further reading: muscle plasticity (396), myofibrillary protein isoforms (453), molecular muscle diversity (52), ryanodine receptor (469), troponin system (490), PV (390), Ca2+ ATPase (320), calequesterin (187), dystrophinopathies (499), calcium release channel diseases (351), and muscle canalopathies (296). . . .