![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
WF Denetclaw , FW Hopf, GA Cox, JS Chamberlain and RA Steinhardt
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
A lack of dystrophin results in muscle degeneration in Duchenne muscular dystrophy. Dystrophin-deficient human and mouse muscle cells have higher resting levels of intracellular free calcium ([Ca2+]i) and show a related increase in single-channel open probabilities of calcium leak channels. Elevated [Ca2+]i results in high levels of calcium- dependent proteolysis, which in turn increases calcium leak channel activity. This process could initiate muscle degeneration by further increasing [Ca2+]i and proteolysis in a positive feedback loop. Here, we tested the direct effect of restoration of dystrophin on [Ca2+]i and channel activity in primary myotubes from mdx mice made transgenic for full-length dystrophin. Transgenic mdx mice have been previously shown to have normal dystrophin localization and no muscle degeneration. Fura- 2 calcium measurements and single-channel patch recordings showed that resting [Ca2+]i levels and open probabilities of calcium leak channels of transgenic mdx myotubes were similar to normal levels and significantly lower than mdx littermate controls (mdx) that lack dystrophin. Thus, restoration of normal calcium regulation in transgenic mdx mice may underlie the resulting absence of degeneration.
This article has been cited by other articles:
|
|
 |
|
  O. Friedrich, M. Both, J. M. Gillis, J. S. Chamberlain, and R. H. A. Fink Mini-dystrophin restores L-type calcium currents in skeletal muscle of transgenic mdx mice J. Physiol., February 15, 2004; 555(1): 251 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Squire, J.M. Raymackers, C. Vandebrouck, A. Potter, J. Tinsley, R. Fisher, J.M. Gillis, and K.E. Davies Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system Hum. Mol. Genet., December 15, 2002; 11(26): 3333 - 3344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Blake, A. Weir, S. E. Newey, and K. E. Davies Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle Physiol Rev, April 1, 2002; 82(2): 291 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Culligan, N. Banville, P. Dowling, and K. Ohlendieck Drastic reduction of calsequestrin-like proteins and impaired calcium binding in dystrophic mdx muscle J Appl Physiol, February 1, 2002; 92(2): 435 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Burkin, G. Q. Wallace, K. J. Nicol, D. J. Kaufman, and S. J. Kaufman Enhanced Expression of the {alpha}7{beta}1 Integrin Reduces Muscular Dystrophy and Restores Viability in Dystrophic Mice J. Cell Biol., March 19, 2001; 152(6): 1207 - 1218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. W. Hopf, P. Reddy, J. Hong, and R. A. Steinhardt A Capacitative Calcium Current in Cultured Skeletal Muscle Cells Is Mediated by the Calcium-specific Leak Channel and Inhibited by Dihydropyridine Compounds J. Biol. Chem., September 13, 1996; 271(37): 22358 - 22367. [Abstract] [Full Text] [PDF]
|
|
