Overactivity of exercise-sensitive cation channels and their impaired modulation by IGF-1 in mdx native muscle fibers: Beneficial effect of pentoxifylline

J. F. Rolland, Annamaria De Luca, Rosa Burdi, Francesca Andreetta, Paolo Confalonieri, Diana Conte Camerino

Research output: Contribution to journalArticlepeer-review

Abstract

Cell-attached patch-clamp recordings on native striated myofibers from adult dystrophic mdx mice revealed a higher occurrence and open probability compared to non-dystrophic wild-type myofibers of a 30 pS voltage-insensitive Ca2+-permeable channel, inhibited by Gd3+, streptomycin and ruthenium red. Myofibers from in vivo exercised animals had higher channel occurrence and/or open probability. Insulin-like growth factor 1 (3.3 nM) induced and/or enhanced channel activity, via PI3 kinase, in wild-type but not in mdx myofibers. Interestingly, in both genotypes the current was silenced by db-cAMP or pentoxifylline, a phosphodiesterase inhibitor. The channel activity/occurrence in pentoxifylline-treated exercised mdx (50 mg/kg/day i.p. for 4-8 weeks) overlapped that of exercised wild-type mice. Thus, a growth factor-sensitive current, likely due to a TRP channel, is activated in vivo by exercise in native striated fibers; its deregulation in the absence of dystrophin may contribute to Ca2+ homeostasis alteration. The possibility to pharmacologically counteract abnormal channel activity discloses important therapeutic application.

Original languageEnglish
Pages (from-to)466-474
Number of pages9
JournalNeurobiology of Disease
Volume24
Issue number3
DOIs
Publication statusPublished - Dec 2006

Keywords

  • Histology
  • IGF-1 and cAMP modulation
  • In vivo exercise
  • mdx mouse
  • Muscular dystrophy
  • Patch-clamp recordings
  • Pentoxifylline
  • Voltage-insensitive cation channels

ASJC Scopus subject areas

  • Neurology

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