title: Store-operated calcium entry contributes to abnormal Ca²⁺ signalling in dystrophic mdx mouse myoblasts.
abstract: Sarcolemma damage and activation of various calcium channels are implicated in altered Ca(2+) homeostasis in muscle fibres of both Duchenne muscular dystrophy (DMD) sufferers and in the mdx mouse model of DMD. Previously we have demonstrated that also in mdx myoblasts extracellular nucleotides trigger elevated cytoplasmic Ca(2+) concentrations due to alterations of both ionotropic and metabotropic purinergic receptors. Here we extend these findings to show that the mdx mutation is associated with enhanced store-operated calcium entry (SOCE). Substantially increased rate of SOCE in mdx myoblasts in comparison to that in control cells correlated with significantly elevated STIM1 protein levels. These results reveal that mutation in the dystrophin-encoding Dmd gene may significantly impact cellular calcium response to metabotropic stimulation involving depletion of the intracellular calcium stores followed by activation of the store-operated calcium entry, as early as in undifferentiated myoblasts. These data are in agreement with the increasing number of reports showing that the dystrophic pathology resulting from dystrophin mutations may be developmentally regulated. Moreover, our results showing that aberrant responses to extracellular stimuli may contribute to DMD pathogenesis suggest that treatments inhibiting such responses might alter progression of this lethal disease.
authors: Nencki Institute of Experimental Biology, Warsaw, Poland; Departments of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA(1).
authors: Marta
authors: M
authors: Onopiuk
authors: School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK; Nencki Institute of Experimental Biology, Warsaw, Poland.
authors: Wojciech
authors: W
authors: Brutkowski
authors: School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
authors: Christopher
authors: C
authors: Young
authors: School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK; Nencki Institute of Experimental Biology, Warsaw, Poland.
authors: Elżbieta
authors: E
authors: Krasowska
authors: Nencki Institute of Experimental Biology, Warsaw, Poland.
authors: Justyna
authors: J
authors: Róg
authors: Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, UK.
authors: Morten
authors: M
authors: Ritso
authors: Nencki Institute of Experimental Biology, Warsaw, Poland.
authors: Sylwia
authors: S
authors: Wojciechowska
authors: School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
authors: Stephen
authors: S
authors: Arkle
authors: Nencki Institute of Experimental Biology, Warsaw, Poland. Electronic address: k.zablocki@nencki.gov.pl.
authors: Krzysztof
authors: K
authors: Zabłocki
authors: School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
authors: Dariusz C
authors: DC
authors: Górecki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels / Q000378:metabolism; D000074287:TRPC6 Cation Channel
chemical_list: D015220:Calcium Channels; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; C096351:transient receptor potential cation channel, subfamily C, member 1; D000255:Adenosine Triphosphate
keywords: Duchenne muscular dystrophy; Myoblasts; STIM1 protein; Store-operated calcium entry; mdx