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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Aug;80(15):4732–4736. doi: 10.1073/pnas.80.15.4732

Increased membrane permeability to chloride in Duchenne muscular dystrophy fibroblasts and its relationship to muscle function.

C N Pato, M H Davis, M J Doughty, S H Bryant, E Gruenstein
PMCID: PMC384118  PMID: 6576355

Abstract

Previous studies have suggested an abnormality in Cl- metabolism in Duchenne muscular dystrophy (DMD) fibroblasts. In order to further characterize this abnormality, we have studied 36Cl- distribution and permeability in 11 DMD and 12 normal fibroblast lines. Under steady-state conditions Cl- efflux in fibroblasts is observed to be biphasic, revealing the presence of two major subcellular compartments. Each compartment contains approximately half of the cellular Cl-. The faster of the two observed efflux components is significantly higher in DMD than in control fibroblasts (P less than 0.001). To determine the results of a similar increase in Cl- permeability on skeletal muscle action potentials, we have simulated the effects of increased Cl- conductance on muscle by using a computer model. Effects on the simulated action potential include lower rates of membrane depolarization, lower overpotential, longer duration, and lower input resistance. These effects are similar to those actually observed in DMD muscle.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adrian R. H., Chandler W. K., Hodgkin A. L. Voltage clamp experiments in striated muscle fibres. J Physiol. 1970 Jul;208(3):607–644. doi: 10.1113/jphysiol.1970.sp009139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adrian R. H., Marshall M. W. Sodium currents in mammalian muscle. J Physiol. 1977 Jun;268(1):223–250. doi: 10.1113/jphysiol.1977.sp011855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Davis M. H., Gelman B. B., Gruenstein E. Decreased structure-linked latency of lysosomal dipeptidyl aminopeptidase-I activity in Duchenne muscular dystrophy fibroblasts. Neurology. 1982 May;32(5):486–491. doi: 10.1212/wnl.32.5.486. [DOI] [PubMed] [Google Scholar]
  4. Davis M. H., Pato C. N., Gruenstein E. Analysis of neurotoxin and mitogen-stimulated sodium transport in human fibroblasts. J Biol Chem. 1982 Apr 25;257(8):4356–4361. [PubMed] [Google Scholar]
  5. DeCoursey T. E., Bryant S. H., Lipicky R. J. Sodium currents in human skeletal muscle fibers. Muscle Nerve. 1982 Oct;5(8):614–618. doi: 10.1002/mus.880050805. [DOI] [PubMed] [Google Scholar]
  6. Eisenberg R. S., Gage P. W. Ionic conductances of the surface and transverse tubular membranes of frog sartorius fibers. J Gen Physiol. 1969 Mar;53(3):279–297. doi: 10.1085/jgp.53.3.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gelman B. B., Davis M. H., Morris R. E., Gruenstein E. Structural changes in lysosomes from cultured human fibroblasts in Duchenne's muscular dystrophy. J Cell Biol. 1981 Feb;88(2):329–337. doi: 10.1083/jcb.88.2.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gelman B. B., Papa L., Davis M. H., Gruenstein E. Decreased lysosomal dipeptidyl aminopeptidase I activity in cultured human skin fibroblasts in Duchenne's muscular dystrophy. J Clin Invest. 1980 Jun;65(6):1398–1406. doi: 10.1172/JCI109804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gruener R., Stern L. Z., Markovitz D., Gerdes C. Electrophysiologic properties of intercostal muscle fibers in human neuromuscular diseases. Muscle Nerve. 1979 May-Jun;2(3):165–172. doi: 10.1002/mus.880020303. [DOI] [PubMed] [Google Scholar]
  10. HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ionasescu V., Lara-Braud C., Zellweger H., Ionasescu R., Burmeister L. Fibroblast cultures in Duchenne muscular dystrophy. Alterations in synthesis and secretion of collagen and noncollagen proteins. Acta Neurol Scand. 1977 May;55(5):407–417. doi: 10.1111/j.1600-0404.1977.tb05659.x. [DOI] [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. Merickel M., Gray R., Chauvin P., Appel S. Electrophysiology of human muscle in culture. Exp Neurol. 1981 May;72(2):281–293. doi: 10.1016/0014-4886(81)90223-5. [DOI] [PubMed] [Google Scholar]
  14. Pickard N. A., Gruemer H. D., Verrill H. L., Isaacs E. R., Robinow M., Nance W. E., Myers E. C., Goldsmith B. Systemic membrane defect in the proximal muscular dystrophies. N Engl J Med. 1978 Oct 19;299(16):841–846. doi: 10.1056/NEJM197810192991601. [DOI] [PubMed] [Google Scholar]
  15. Stefani E., Chiarandini D. J. Ionic channels in skeletal muscle. Annu Rev Physiol. 1982;44:357–372. doi: 10.1146/annurev.ph.44.030182.002041. [DOI] [PubMed] [Google Scholar]
  16. Villereal M. L., Cook J. S. Regulation of active amino acid transport by growth-related changes in membrane potential in a human fibroblast. J Biol Chem. 1978 Nov 25;253(22):8257–8262. [PubMed] [Google Scholar]
  17. Wyatt P. R., Cox D. M. Duchenne's muscular dystrophy: studies in cultured fibroblasts. Lancet. 1977 Jan 22;1(8004):172–174. doi: 10.1016/s0140-6736(77)91768-8. [DOI] [PubMed] [Google Scholar]

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