Hypoosmotic shocks induce elevation of resting calcium level in Duchenne muscular dystrophy myotubes contracting in vitro.
In Duchenne muscular dystrophy (DMD) muscle cells which lack dystrophin, contraction seems to be a dominant factor contributing to the abnormal elevated intracellular calcium level. Human normal and DMD contracting myotubes cocultured with nervous cells were exposed to a hypotonic medium to mimic contraction-induced mechanical stress on the membrane, and the cytoplasmic calcium activity was simultaneously monitored (Indo-1). Hypotonic shocks induced a reversible [Ca2+]i increase in 81% of the DMD cells vs. 54% of control. In addition, responses were qualitatively different: most of DMD myotubes displayed a fast increase of Ca2+ flowing from the edge of the myotube while the response in normal cells was slow and diffuse. The fact that these responses were not affected by ryanodine, was in favour of an external source of Ca2+ involved in the hypoosmotic shocks. The localized increase of Ca2+ in DMD myotubes, inhibited by Gd3+, could result from sites of high mechanosensitive channel activity or density which could constitute a pathway for Ca2+ entry provided these cells contract.
Imbert
N
N
Laboratoire de Physiologie Générale, CNRS 1869, Université de Poitiers, France.
Vandebrouck
C
C
Constantin
B
B
Duport
G
G
Guillou
C
C
Cognard
C
C
Raymond
G
G
D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured / Q000378:metabolism; D016189:Dystrophin / Q000172:deficiency; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D007038:Hypotonic Solutions; D007552:Isotonic Solutions; D008856:Microscopy, Fluorescence; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology*; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000473:pathology; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D012433:Ryanodine / Q000494:pharmacology
D016189:Dystrophin; D007038:Hypotonic Solutions; D007552:Isotonic Solutions; D012433:Ryanodine; D005682:Gadolinium; D002118:Calcium