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
| HERO ID | 6315826 |
|---|---|
| In Press | No |
| Year | 2006 |
| Title | Overactivity of exercise-sensitive cation channels and their impaired modulation by IGF-1 in mdx native muscle fibers: Beneficial effect of pentoxifylline |
| Authors | Rolland, JF; De Luca, A; Burdi, R; Andreetta, F; Confalonieri, P; Camerino, DC |
| Journal | Neurobiology of Disease |
| Volume | 24 |
| Issue | 3 |
| Page Numbers | 466-474 |
| 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. |
| Doi | 10.1016/j.nbd.2006.08.010 |
| Pmid | 17010631 |
| Wosid | WOS:000242298900004 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | in vivo exercise; muscular dystrophy; mdx mouse; patch-clamp recordings; voltage-insensitive cation channels; IGF-1 and cAMP modulation; pentoxifylline; histology |