Functional Study of Sarcoglycan in Cardiomyopathic Muscle Cells

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Deficiency of delta-sarcoglycan, a component of the dystrophin-glycoprotein complex, causes cardiomyopathy and skeletal muscle dystrophy in BIO14.6 hamsters. Using cultured myotubes (for 2-4 days) prepared from muscle of normal and BIO14.6 hamsters (30-40 day old), we investigated the possibility that the delta-sarcoglycan in calcium metabolism which may ultimately leads to myocyte damage. Immunoblot analysis revealed that the contents of membrane proteins involved in cell Ca handling such as L-type Ca channel, ryanodine receptor, SR-CaATPase, Na/Ca exchanger were not different between control and BI014.6 myotubes. ^<45>Ca^<2+> influx into BIO14.6 myotubes 2+ under resting conditions was significantly higher (up to1.8-fold at 5 min) than in controls, suggesting that Ca^<2+> influx is activated in BIO 14.6 myotubes. When these cells were subjected to cyclic elongation of up to 20 % for 1h, a marked increase in creatine phosphokinase (CK) release into the medium was obsereved in only BIO14.6 myotubes. 100μM GdCl_3 reduced ^<45>Ca^<2+> influx and CK release. Transfection of delta sarcoglycan using 2+ adenovirus vector also rescue abnormal calcium metabolism and CK release The increased resting Ca influx in BIO14.6 myotubes may be due to the increased basal activity of stretch-activated cation channels detected in these myotubes and these results suggest a possible mechanism for cell damage in this animal model of muscular dystrophy.