Spontaneous calcium transients manifest in the regenerating muscle and are necessary for skeletal muscle replenishment.
Tissue regeneration entails replenishing of damaged cells, appropriate cell differentiation and inclusion of regenerated cells into functioning tissues. In adult humans, the capacity of the injured spinal cord and muscle to self-repair is limited. In contrast, the amphibian larva can regenerate its tail after amputation with complete recovery of muscle, notochord and spinal cord. The cellular and molecular mechanisms underlying this phenomenon are still unclear. Here we show that upon injury muscle cell precursors exhibit Ca(2+) transients that depend on Ca(2+) release from ryanodine receptor-operated stores. Blockade of these transients impairs muscle regeneration. Furthermore, inhibiting Ca(2+) transients in the regenerating tail prevents the activation and proliferation of muscle satellite cells, which results in deficient muscle replenishment. These findings suggest that Ca(2+)-mediated activity is critical for the early stages of muscle regeneration, which may lead to developing effective therapies for tissue repair.
Department of Physiology & Membrane Biology and Shriners Hospital for Children Northern California, University of California Davis School of Medicine, 2425 Stockton Boulevard, Sacramento, CA 95817, United States.
Michelle Kim
MK
Tu
Department of Physiology & Membrane Biology and Shriners Hospital for Children Northern California, University of California Davis School of Medicine, 2425 Stockton Boulevard, Sacramento, CA 95817, United States. Electronic address: lnborodinsky@ucdavis.edu.
Laura Noemi
LN
Borodinsky
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D002478:Cells, Cultured; D007814:Larva; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000502:physiology* / Q000601:surgery; D032446:Myoblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D012038:Regeneration / Q000187:drug effects; D044968:Regenerative Medicine; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects / Q000502:physiology*; D014982:Xenopus laevis
D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine
Calcium stores; Muscle regeneration; Muscle satellite cells; Xenopus