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6315826 
Journal Article 
Overactivity of exercise-sensitive cation channels and their impaired modulation by IGF-1 in mdx native muscle fibers: Beneficial effect of pentoxifylline 
Rolland, JF; De Luca, A; Burdi, R; Andreetta, F; Confalonieri, P; Camerino, DC 
2006 
1 
Neurobiology of Disease
ISSN: 0969-9961
EISSN: 1095-953X 
24 
3 
466-474 
English 
17010631 
WOS:000242298900004 
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. 
in vivo exercise; muscular dystrophy; mdx mouse; patch-clamp recordings; voltage-insensitive cation channels; IGF-1 and cAMP modulation; pentoxifylline; histology