Although several lines of evidence link muscle-derived oxidants and inflammation to skeletal muscle wasting via regulation of apoptosis and proteolysis, little information is currently available on muscle repair. The present work was designed to study oxidative stress response, inflammatory cytokines, apoptotic, or proteolytic pathways during the early (1 and 5 days) and later (14 days) stages of the regrowth process subsequent to 14 days of hindlimb unloading. During the early stages of reloading, muscle mass recovery (day 5) was facilitated by transcriptional downregulation (day 1) of pathways involved in muscle proteolysis [mu-calpain, atrogin-1/muscle atrophy F-box (MAFbx), and muscle RING finger-1/(MuRF1) mRNA] and upregulation of an autophagy-related protein Beclin-1 (day 5). At the same time, oxidative stress (glutathione vs. glutathione disulfide ratio, superoxide dismutase, catalase activities) remained still enhanced, whereas the increased uncoupling protein 3 gene expression recovered. Increased caspase-9 (mitochondrial-driven apoptosis) and decreased caspase-12 (sarcoplasmic reticulum-mediated apoptosis) activation was also normalized at early stages (day 5). Conversely, the receptor-mediated apoptotic pathway initiated by ligand-induced (tumor necrosis factor-alpha, TNF-alpha) binding and promoting the activation of caspase-8 remained elevated until 14 days. Our data suggest that at early stages, muscle repair is mediated via the modulation of mitochondrial-driven apoptosis and muscle proteolysis. Despite full muscle mass recovery, oxidative stress and TNF-alpha-mediated apoptotic pathway are still activated till later stages of muscle remodeling.

Background:The composition of voltage-gated calcium channels is important for function. Results: In C. elegans, calcium currents are altered in mutants of one main subunit (EGL-19) or the accessory subunits UNC-36 and CCB-1. Conclusion: Voltage-gated calcium channels of C. elegans striated muscles are composed of EGL-19, UNC-36, and CCB-1. Significance: C. elegans could be a new model to study the roles of accessory subunits.

In skeletal muscle, sarcoplasmic reticulum (SR) Ca2+ depletion is suspected to trigger a calcium entry across the plasma membrane and recent studies also suggest that the opening of channels spontaneously active at rest and possibly involved in Duchenne dystrophy may be regulated by SR Ca 2+ depletion. Here we simultaneously used the cell-attached and whole-cell voltage-clamp techniques as well as intracellular Ca 2+ measurements on single isolated mouse skeletal muscle fibres to unravel any possible change in membrane conductance that would depend upon SR Ca 2+ release and/or SR Ca 2+ depletion. Delayed rectifier K + single channel activity was routinely detected during whole-cell depolarizing pulses. In addition the activity of channels carrying unitary inward currents of ∼1.5 pA at −80 mV was detected in 17 out of 127 and in 21 out of 59 patches in control and mdx dystrophic fibres, respectively. In both populations of fibres, large whole-cell depolarizing pulses did not reproducibly increase this channel activity. This was also true when, repeated application of the whole-cell pulses led to exhaustion of the Ca 2+ transient. SR Ca2+ depletion produced by the SR Ca 2+ pump inhibitor cyclopiazonic acid (CPA) also failed to induce any increase in the resting whole-cell conductance and in the inward single channel activity. Overall results indicate that voltage-activated SR Ca 2+ release and/or SR Ca 2+ depletion are not sufficient to activate the opening of channels carrying inward currents at negative voltages and challenge the physiological relevance of a store-operated membrane conductance in adult skeletal muscle.