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Regulation of muscle contraction is a very cooperative process. The presence of tropomyosin on the thin filament is both necessary and sufficient for cooperativity to occur. Data recently obtained with various tropomyosin isoforms and mutants help us to understand better the structural requirements in the thin filament for cooperative protein interactions. Forming an end-to-end overlap between neighboring tropomyosin molecules is not necessary for the cooperativity of the thin filament acti­vation. When direct contacts between tropomyosin molecules are disrupted, the conformational changes in the filament are most probably transmitted cooperatively through actin subunits, although the exact nature of these changes is not known. The function of tropomyosin ends, alternatively expressed in various isoforms, is to confer specific actin affinity. Tropomyosin's affinity or actin is directly related to the size of the apparent cooperative unit defined as the number of actin subunits turned into the active state by binding of one myosin head. Inner sequences of tropomyosin, particu­larly actin-binding periods 3 to 5, play crucial role in myosin-induced activation of the thin filament. A plausible mechanism of tropomyosin function in this process is that inner tropomyosin regions are either specifically recognized by myosin or they define the right actin conformation required for tropomyosin movement from its blocking position.
Cell motility processes in non-muscle cells depend on the activity of motor proteins that bind to either microtubules or actin filaments. From presently available data it must be concluded that the driving force is generated by transient interaction of the respective motors with microtubules or actin filaments which then activates the binding and hydrolysis of ATP. This reaction results in an abrupt discharge of the motor molecule, the direction of which is determined by the spatial orientation of its binding to the helical and polar vehicle. The latter is thereby propelled in its length direction and simultaneously undergoes an axial rotation, while the expelled motor exerts an oppositely directed current in the surrounding fluid, comparable to jet propulsion. Force production, propulsion velocities and energy requirements known from in vitro studies comply with those derived from the theory. The theory opens new ways for the understanding of cellular activities such as particle transport, mitosis and morphodynamics.
This brief review attempts to summarize some of the major phases of muscle research from Leeuwenhoek's description of sarcomeres in 1674, through Galvani's observation of animal electricity in 1791, to the discovery of Ca2+ as the key messenger in the coupling of nerve excitation to muscle contraction. The emerging molecular mechanism of the contraction process is one of the great achievements of biology, reflecting the intimate links between physics, chemistry and the life Sciences in the solution of biological problems.
Vitamin D deficiency is associated with muscle weakness. It is unknown, however, how supra-physiological levels of vitamin D affect skeletal muscle. To investigate the effects of increased serum vitamin D (1,25 (OH)2D3 or 1,25D) levels on the contractile properties of the medial gastrocnemius muscle, adult and old female Fischer344 x Brown Norway F1 rats were orally treated with vehicle or the vitamin D analogue alfacalcidol for 1 or 6 weeks. Alfacalcidol treatment resulted in elevated 1,25D serum levels. This was accompanied by hypercalcaemia and a reduction in body mass, the latter largely attributable to a reduced food intake. However, kidney function, as reflected by normal creatinine serum levels, as well as heart mass were unaffected. The 17% reduction in maximal isometric force and power was explicable by a similar loss of muscle mass. The force-frequency relationship of the 6-week-treated old rats was shifted to the left, but neither the shape of the force-velocity relationship nor the fatigability of the muscle were altered. Supra-physiological doses of vitamin D were accompanied by significant reductions in body and muscle mass, but not by an improvement in muscle functioning. Weight loss was largely due to a reduced food intake, while the left shift in the force-frequency relation may be due to increased 1,25D levels.
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