Dystrophin is required for the normal function of the cardio-protective K ATP channel in cardiomyocytes

Laura Graciotti, Jodi Becker, Anna Luisa Granata, Antonio Domenico Procopio, Lino Tessarollo, Gianluca Fulgenzi

Research output: Contribution to journalArticle


Duchenne and Becker muscular dystrophy patients often develop a cardiomyopathy for which the pathogenesis is still unknown. We have employed the murine animal model of Duchenne muscular dystrophy (mdx), which develops a cardiomyopathy that includes some characteristics of the human disease, to study the molecular basis of this pathology. Here we show that the mdx mouse heart has defects consistent with alteration in compounds that regulate energy homeostasis including a marked decrease in creatine-phosphate (PC). In addition, the mdx heart is more susceptible to anoxia than controls. Since the cardio-protective ATP sensitive potassium channel (K ATP) complex and PC have been shown to interact we investigated whether deficits in PC levels correlate with other molecular events including K ATP ion channel complex presence, its functionality and interaction with dystrophin. We found that this channel complex is present in the dystrophic cardiac cell membrane but its ability to sense a drop in the intracellular ATP concentration and consequently open is compromised by the absence of dystrophin. We further demonstrate that the creatine kinase muscle isoform (CKm) is displaced from the plasma membrane of the mdx cardiac cells. Considering that CKm is a determinant of K ATP channel complex function we hypothesize that dystrophin acts as a scaffolding protein organizing the K ATP channel complex and the enzymes necessary for its correct functioning. Therefore, the lack of proper functioning of the cardio-protective K ATP system in the mdx cardiomyocytes may be part of the mechanism contributing to development of cardiac disease in dystrophic patients.

Original languageEnglish
Article numbere27034
JournalPLoS One
Issue number10
Publication statusPublished - Nov 4 2011


ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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