How calcium influx through calcium leak channels is responsible for the elevated levels of calcium-dependent proteolysis in dystrophic myotubes.
Duchenne muscular dystrophy patients lack the protein dystrophin which is an essential link in the complex of proteins that connect the cytoskeleton to the extracellular matrix. In mechanically stressed tissues such as muscle, transient sarcolemmal microdisruptions are normal, but in dystrophic muscle cells the frequency of these microdisruptions is greatly increased. Although both normal and dystrophic cells are able to actively repair these microdisruptions, calcium entry through the more frequent sarcolemmal microdisruptions of dystrophic cells results in an increased calcium-dependent proteolysis that alters the activity of the calcium leak channel. The accumulation of abnormally active calcium leak channels over time results in a gradual loss of calcium homeostasis and eventual cell death.
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720-3200, USA.
J M
JM
Alderton
R A
RA
Steinhardt
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D016189:Dystrophin / Q000235:genetics / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D006868:Hydrolysis; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D012508:Sarcolemma / Q000502:physiology
D015220:Calcium Channels; D016189:Dystrophin; D009124:Muscle Proteins; D002154:Calpain; D002118:Calcium