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 dystrophi n, contraction seems to be a dominant factor contributing to the abnor mal elevated intracellular calcium level. Human normal and DMD contrac ting myotubes cocultured with nervous cells were exposed to a hypotoni c medium to mimic contraction-induced mechanical stress on the membran e, and the cytoplasmic calcium activity was simultaneously monitored ( Indo-1). Hypotonic shocks induced a reversible [Ca2+](i) increase in 8 1% of the DMD cells vs. 54% of control. In addition, responses were qu alitatively different: most of DMD myotubes displayed a fast increase of Ca2+ flowing from the edge of the myotube while the response in nor mal cells was slow and diffuse. The fact that these responses were not affected by ryanodine, was in favour of an external source of Ca2+ in volved in the hypoosmotic shocks. The localized increase of Ca2+ in DM D myotubes, inhibited by Gd3+, could result from sites of high mechano sensitive channel activity or density which could constitute a pathway for Ca2+ entry provided these cells contract.