Institute of Biomedical and Biomolecular Science (IBBS)

Molecular and genetic medicine

P2 receptors in muscular dystrophy

Our research is focused on Duchenne muscular dystrophy (DMD). We aim to understand the pathogenesis and to help developing an effective treatment.

DMD is the most common and debilitating genetic form of muscular dystrophy and the second most common inherited disorder in man. The disease is caused by the absence of the cytoskeletal protein, dystrophin leading to abnormalities of the dystrophin-associated protein (DAP) complex. Pathological cellular hallmarks of Duchenne muscular dystrophy include, amongst others, abnormal calcium homeostasis.

We have found that in dystrophic muscle a purinergic dystrophic phenotype arises; exposure to extracellular ATP triggered strong increase in cytoplasmic Ca2+ concentrations (Yeung et al, 2006). Our results suggest that altered function of P2X receptors may be an important contributor to pathogenic Ca2+ entry in dystrophic mouse muscle and may have implications for the pathogenesis of DMD and other muscular dystrophies (Jiang et al, 2005, Yeung et al, 2004).

Fig. 1

Stimulations by extracellular nucleotides increase cytoplasmic Ca2+ levels in dystrophic (SC5) and control (IMO) myoblasts.  Reproducible traces in stimulations by ATP or ADP (each 1mM) are shown for (A) SC5 and (B) IMO cells in medium containing 2 mM Ca2+ and for both cell lines in calcium-free medium (C). Note the much higher increase in intracellular Ca2+ in SC5 cells.  (D) In dystrophic cells emptying Ca2+ stores abolished the effect of ADP but did not affect the response to ATP (Yeung et al, 2006).