Ca ͉ muscle ͉ regulation ͉ structure

BackgroundRestless Legs Syndrome is very common in hemodialysis patients however there are no comparative studies assessing the effectiveness of a non-pharmacological treatment to a classical treatment on parameters related to syndromes’ severity and quality of life.MethodsIn this randomized, partially double blind, placebo controlled trial, thirty two hemodialysis patients with restless legs syndrome were randomly assigned into three groups: 1) the exercise training group (N = 16), 2) the dopamine agonists group (ropinirole 0.25 mg/d) (N = 8) and 3) the placebo group (N = 8). The intervention programs lasted 6 months. Restless Legs Syndrome severity was assessed using the international severity scale, physical performance by a battery of tests, muscle size and composition by computed tomography, body composition by Dual Energy X Ray Absorptiometry, while depression score, sleep quality, daily sleepiness and quality of life were assessed through questionnaires.ResultsExercise training and dopamine agonists were effective in reducing syndrome’s symptoms by 46% (P = 0.009) and 54% (P = 0.001) respectively. Within group changes revealed that both approaches significantly improved quality of life (P < 0.05), however, only the dopamine agonists significantly improved sleep quality (P = 0.009). Within group changes showed a tendency for lean body mass improvements with dopamine agonists, this reached statistical significance only with the exercise training (P = 0.014), which also reduced fat infiltration in muscles (P = 0.044) and improved physical performance (P > 0.05) in various tests. Between group changes detect significant improvements with both exercise and dopamine agonists in depression score (P = 0.003), while only the dopamine agonist treatment was able to significantly improve sleep quality, compared to exercise and placebo (P = 0.016).ConclusionsA 6-month exercise training regime was as effective as a 6-month low dosage dopamine agonist treatment in reducing restless legs syndrome symptoms and improving depression score in uremic patients. Further research is needed in order to show whether a combination treatment could be more beneficial for the amelioration of RLS.Trial registrationNCT00942253

The mechanisms responsible for the inhibition of shortening velocity that occurs during muscle fatigue have not been completely elucidated. Phosphorylation of the myosin regulatory light chain (RLC) occurs during heavy use; however, previous reports on its role in affecting velocity have been equivocal. To further understand the process of fatigue, we varied the levels of myosin RLC phosphorylation (from 10 to Ͼ50%) and the concentrations of protons (from pH 7 to 6.2) and phosphate (from 5 to 30 mM), all of which change during fatigue. We measured the mechanics of permeable rabbit psoas fibers at a temperature closer to physiological (30°C), using a temperature jump protocol to briefly activate the fibers at the higher temperature to preserve sarcomere homogeneity. Although lowered pH alone had an effect on velocity, it was the three factors together, i.e., high phosphorylation, low pH, and high phosphate, that acted synergistically to inhibit fiber velocity by ϳ40%. Our data demonstrate that in conditions that simulate physiological muscle fatigue, myosin phosphorylation does contribute to the inhibition of contraction velocity of fully activated fast muscle fibers. mechanics; myosin; pH IN SKELETAL MUSCLE FATIGUE, tension, shortening velocity and the rate of energy use are all inhibited (10, 32). Many studies have explored whether the buildup of the products of ATP hydrolysis [ADP, inorganic phosphate (P i ), and protons] directly affects the actomyosin interaction and may thus inhibit shortening velocity. Although several metabolites do affect fiber mechanics, they do not quantitatively account for the inhibition of shortening velocity observed in living fibers (see e.g., Refs. 10, 21, 32). Other factors to consider are any alterations in the structure and function of myosin per se, and specifically, the role of myosin light chain as a regulator of muscle mechanics. In fast fibers, both myosin heavy chain and myosin light chain composition have been found to be important determinants of unloaded shortening velocity (1), although the exact mechanism by which various isoforms of myosin light chain modulate velocity is not clear.There is evidence that myosin regulatory light chain (RLC) phosphorylation can alter the interaction of myosin and actin and result in tension potentiation. In myosin, the RLC is phosphorylated by a calcium-activated kinase (MLCK), leading to increased RLC phosphorylation levels during sustained activity or fatigue of skeletal muscles. RLC phosphorylation was found to correlate with twitch tension potentiation after a tetanic contraction or during a train of twitches in vivo (26) and to increase tension in permeable fibers at low levels of calcium activation, providing one possible molecular mechanism for the correlation between myosin phosphorylation and twitch potentiation (25). The role of RLC phosphorylation in increasing twitch tension in vivo was further established in mice lacking MLCK, where twitch potentiation was almost totally eliminated (37).Phosphorylation of the RLC is mini...