A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channel

Yuko Iwata, Yuki Katanosaka, Yuji Arai, Kazuo Komamura, Kunio Miyatake, Munekazu Shigekawa

Research output: Contribution to journalArticlepeer-review

227 Citations (Scopus)


Disruption of the dystrophin-glycoprotein complex caused by genetic defects of dystrophin or sarcoglycans results in muscular dystrophy and/or cardiomyopathy in humans and animal models. However, the key early molecular events leading to myocyte degeneration remain elusive. Here, we observed that the growth factor-regulated channel (GRC), which belongs to the transient receptor potential channel family, is elevated in the sarcolemma of skeletal and/or cardiac muscle in dystrophic human patients and animal models deficient in dystrophin or δ-sarcoglycan. However, total cell GRC does not differ markedly between normal and dystrophic muscles. Analysis of the properties of myotubes prepared from δ-sarcoglycan-deficient BlO14.6 hamsters revealed that GRC is activated in response to myocyte stretch and is responsible for enhanced Ca2+ influx and resultant cell damage as measured by creatine phosphokinase efflux. We found that cell stretch increases GRC translocation to the sarcolemma, which requires entry of external Ca2+. Consistent with these findings, cardiac-specific expression of GRC in a transgenic mouse model produced cardiomyopathy due to Ca2+ overloading, with disease expression roughly parallel to sarcolemmal GRC levels. The results suggest that GRC is a key player in the pathogenesis of myocyte degeneration caused by dystrophinglycoprotein complex disruption.

Original languageEnglish
Pages (from-to)957-967
Number of pages11
JournalJournal of Cell Biology
Issue number5
Publication statusPublished - Jun 9 2003
Externally publishedYes


  • Calcium entry
  • Cardiomyopathy
  • Dystrophin-glycoprotein complex
  • Muscular dystrophy
  • Nonselective cation channel

ASJC Scopus subject areas

  • Cell Biology


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