ABSTRACT
Although the primary deficiency in dystrophin and the concomitant reduction in surface glycoproteins are well established factors in the molecular pathogenesis of Duchenne muscular dystrophy, the pathophysiological events that render a muscle fibre more sus ceptible to necrosis are not well understood. One proposed mechanism involves abnormal calcium homeostasis in mechanically stressed fibres that eventually leads to skeletal muscle weakness. This chapter examines the calcium hypothesis of muscular dystrophy and outlines how unbalanced ion cycling through the sarcolemma and the sarcoplasmic reticulum may contribute to enhanced degradation of muscle proteins. Studying calcium handling in muscu lar dystrophy is not only important for increasing our knowledge on the multifaceted process of muscle degeneration, but might also have implications for the future design of therapeutic approaches to treating x-linked muscular dystrophy. In this respect, it is encouraging that the pharmacological elimination of Ca2+-dependent proteolysis counteracts dystrophic changes and that the removal of excess cytosolic Ca2+ appears to convey natural protection to dystrophin-deficient fibres.
