Changes in cytosolic Ca2+ dynamics in the sarcoplasmic reticulum associated with the pathology of Duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is a life-limiting X-linked genetic disorder caused by a lack of the membrane-associated protein dystrophin. The absence of dystrophin increases the susceptibility of muscle fibers to damage. Repeated damage results in ineffective muscle repair and the development of pseudo-hypertrophied muscles; these bulky muscles are weak despite their size. The mechanisms underlying the functional impairments in dystrophic muscle have not yet been fully determined. However, several recent studies indicate that elevated intracellular Ca2+ homeostasis is a cause or facilitator of the development of muscle weakness in DMD. This review focuses on abnormalities of Ca2+ homeostasis and the possibilities for treatment by counteracting the Ca2+ dysregulation.

Keywords

• duchenne muscular dystrophy
• ca2+ homeostasis
• sarcoplasmic reticulum (sr)
• ryanodine receptor (ryr1)
• sarcoplasmic endoplasmic reticulum atpase (serca)