Calcium homeostasis and ultrastructural studies in a patient with limb girdle muscular dystrophy type 2C

There is increasing evidence that gamma-sarcoglycan is absent and other sar coglycans ate reduced in patients with the limb-girdle muscular dystrophy t ype 2C (LGMD2C) form of severe childhood autosomal recessive muscular dystr ophy. In the present investigation, we combined microspectrofluorimetry and electron microscopy techniques to investigate the physiological function a nd the ultrastructure of control and LGMD2C myotubes, Results obtained from Ca2+ measurements showed that the resting level of the cytosolic free calc ium ([Ca2+](i)) in control myotubes was 73+/-3.4 nmol/l (mean+/-SE, n= 35) and in LGMD2C myotubes was 69+/-4 nmol/l (n=44). Carbachol (CCh, 10 mu mol/ l) induced 335+/-10 nmol/l (n=8) rise in [Ca2+](i) in control myotubes and 531.9+/-32 nmol/l (n=23) in LGMD2C myotubes. Similarly, elevations of [Ca2](i), by 3 5 mmol/l K+ were 324+/-32 nmol/l (n=8) in control myotubes and 4 42.8+/-24 nmol/l (n=22) in LGMD2C myotubes. Caffeine (10 mmol/l) activated similar [Ca2+](i) peaks in control and LGMD2C myotubes but induced a biphas ic response in LGMD2C in four out of 12 myotubes and only a monophasic resp onse in control myotubes, The ultrastructural results showed that the plasm a membrane was abnormally indented and convoluted in both the LGMD2C biopsy and the LGMD2C cultured myotubes. It is suggested that the reduction in co mponents of the dystrophin-glycoprotein complex results in the instability and an increase in the surface area of the plasma membrane, which may resul t in a higher population of Ca2+ channels in the LGMD2C myotubes.