2+, activated calpain and accelerated migration. These effects were not observed in TRPC1-knockdown cells. We therefore suggest that entry of Ca 2+ through TRPC1 channels induces a transient activation of calpain and subsequent proteolysis of MARCKS, which allows in turn, myoblast migration and fusion.

Skeletal muscle contraction is reputed not to depend on extracellular Ca2+. Indeed, stricto sensu, excitation-contraction coupling does not necessitate entry of Ca2+. However, we previously observed that, during sustained activity (repeated contractions), entry of Ca2+ is needed to maintain force production. In the present study, we evaluated the possible involvement of the canonical transient receptor potential (TRPC)1 ion channel in this entry of Ca2+ and investigated its possible role in muscle function. Patch-clamp experiments reveal the presence of a small-conductance channel (13 pS) that is completely lost in adult fibers from TRPC1(-/-) mice. The influx of Ca2+ through TRPC1 channels represents a minor part of the entry of Ca(2+) into muscle fibers at rest, and the activity of the channel is not store dependent. The lack of TRPC1 does not affect intracellular Ca2+ concentration ([Ca2+](i)) transients reached during a single isometric contraction. However, the involvement of TRPC1-related Ca2+ entry is clearly emphasized in muscle fatigue. Indeed, muscles from TRPC1(-/-) mice stimulated repeatedly progressively display lower [Ca2+](i) transients than those observed in TRPC1(+/+) fibers, and they also present an accentuated progressive loss of force. Interestingly, muscles from TRPC1(-/-) mice display a smaller fiber cross-sectional area, generate less force per cross-sectional area, and contain less myofibrillar proteins than their controls. They do not present other signs of myopathy. In agreement with in vitro experiments, TRPC1(-/-) mice present an important decrease of endurance of physical activity. We conclude that TRPC1 ion channels modulate the entry of Ca(2+) during repeated contractions and help muscles to maintain their force during sustained repeated contractions.

The effect of creatine (Cr) supplementation on muscle function and body composition of 12 boys with Duchenne muscular dystrophy and three with Becker dystrophy was evaluated by a randomized double-blind cross-over study (3 g Cr or maltodextrin daily for 3 months, with wash-out period of 2 months). After placebo, no change was observed in maximal voluntary contraction (MVC) and resistance to fatigue, whereas total joint stiffness (TJS) was increased by approximately 25% (P < 0.05). The patients receiving Cr did not show any change in TJS, improved MVC by 15% (P = 0.02), and almost doubled their resistance to fatigue (P < 0.001). In patients still independent of a wheelchair (n = 5), bone mineral density increased by 3% (P < 0.05), and urinary excretion of collagen type I cross-linking N-telopeptide declined to about one third (P < 0.001) after Cr. No adverse effect was observed. Thus, Cr may provide some symptomatic benefit in these patients.

No abstract

The increase in lean body mass often reported after creatine supplementation could be mediated by signaling pathway(s) involving IGF and 4E-BP1.

BackgroundAtypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade–based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.MethodsTo evaluate this strategy’s effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016.ResultsThe first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients.ConclusionsResults from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.

. No effect of creatine supplementation on human myofibrillar and sarcoplasmic protein synthesis after resistance exercise. Am J Physiol Endocrinol Metab 285: E1089-E1094, 2003. First published June 24, 2003 10.1152/ajpendo.00195.2003.-Muscle hypertrophy during resistance training is reportedly increased by creatine supplementation. Having previously failed to find an anabolic effect on muscle protein turnover at rest, either fed or fasted, we have now examined the possibility of a stimulatory effect of creatine in conjunction with acute resistance exercise. Seven healthy men (body mass index, 23 Ϯ 2 kg/m 2 , 21 Ϯ 1 yr, means Ϯ SE) performed 20 ϫ 10 repetitions of leg extension-flexion at 75% one-repetition maximum in one leg, on two occasions, 4 wk apart, before and after ingesting 21 g/day creatine for 5 days. The subjects ate ϳ21 g maltodextrin ϩ 6 g protein/h for 3 h postexercise. We measured incorporation of [1-13 C]leucine into quadriceps muscle proteins in the rested and exercised legs. Leg protein breakdown (as dilution of [ 2 H5]phenylalanine) was also assessed in the exercised and rested leg postexercise. Creatine supplementation increased muscle total creatine by ϳ21% (P Ͻ 0.01). Exercise increased the synthetic rates of myofibrillar and sarcoplasmic proteins by two-to threefold (P Ͻ 0.05), and leg phenylalanine balance became more positive, but creatine was without any anabolic effect. skeletal muscle; protein turnover THE USE OF CREATINE SUPPLEMENTATION as an ergogenic aid has increased markedly, especially among athletes requiring high power outputs during so-called explosive events. In investigating the possible mechanisms for the claimed improvements in performance, many workers have reported that creatine supplementation is accompanied by a significant increase in lean body mass (1,2,4,9,14). There is evidence that the increase in muscle mass does not simply represent an increase in total body water but is mainly intracellular, suggesting that the body cell dry mass has increased (10). Also, there are a number of reports showing increases in muscle fiber area as a result of consuming creatine while training using resistance exercise (29, 30) or during treatment of patients with muscle atrophy (13, 28).The mechanism of the creatine-associated effect on muscle mass is unknown. If it is the result of a direct effect of creatine, it should stimulate muscle protein synthesis or decrease muscle protein breakdown. Increased creatine availability has been reported in studies of animal skeletal and cardiac muscle in vitro to stimulate protein synthesis (15,16,33), although other investigators (11) were unable to confirm this.In starting to investigate the possible effects on human muscle, we began by studying the effect of creatine supplementation on human muscle protein turnover at rest in the fasted and fed conditions (20). In that study, we measured myofibrillar protein synthesis and leg protein breakdown in healthy young men before and after 5 days of dietary creatine supplementation sufficient to r...

Addition of creatine to the di¡erentiation medium of C 2 C 12 cells leads to hypertrophy of the myotubes. To investigate the implication of insulin-like growth factor I (IGF-I) and myogenic regulatory factors (MRFs) in this hypertrophy, their mRNA levels were assessed during the ¢rst 72 h of di¡erentia-tion. Creatine signi¢cantly increased the IGF-I mRNA level over the whole investigated period of time, whereas the MRF mRNA levels were only augmented at precise moments, suggesting a general activation mechanism for IGF-I and a speci¢cally regulated mechanism for MRF transcription. Our results suggest therefore that creatine-induced hypertrophy of C 2 C 12 cells is at least partially mediated by overexpression of IGF-I and MRFs. ß