INCREASED EXPRESSION of ACETYLCHOLINE RECEPTORS in the DIAPHRAGM MUSCLE of MDX MICE

INCREASED EXPRESSION of ACETYLCHOLINE RECEPTORS in the DIAPHRAGM MUSCLE of MDX MICE

Author Ghedini, Paulo C. Autor UNIFESP Google Scholar
Viel, Tania A. Autor UNIFESP Google Scholar
Honda, Luciana Autor UNIFESP Google Scholar
Avellar, Maria Christina W. Autor UNIFESP Google Scholar
Godinho, Rosely O. Autor UNIFESP Google Scholar
Lima-Landman, Maria Teresa R. Autor UNIFESP Google Scholar
Lapa, Antonio J. Autor UNIFESP Google Scholar
Souccar, Caden Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract The absence of dystrophin in Duchenne muscular dystrophy (DMD) and in the mutant mdx mouse causes muscle degeneration and disruption of the neuromuscular junction. Based on evidence from the denervation-like properties of these muscles, we assessed the ligand-binding constants of nicotinic acetylcholine receptors (nAChRs) and the mRNA expression of individual subunits in membrane preparations of diaphragm muscles from adult (4-month-old) and aged (20-month-old) control and mdx mice. the concentration of nAChRs as determined by the maximal specific [(125)I]-alpha-bungarotoxin binding (Bmax) in the muscle membranes did not change with aging in both animal strains. When compared to age-matched control groups, the Bmax in mdx muscles was increased by 65% in adults, and by 103% in aged mice with no alteration of toxin affinity for nAChRs. Reverse-transcription polymerase chain reaction assays showed that mRNA transcripts for the nAChR alpha 1, gamma, alpha 7, and beta 2, but not the epsilon subunits, were more abundant in mdx than in control muscles. the results indicate increased expression of extrajunctional nAChRs in the mdx diaphragm and reflect impairment of nAChR regulation in dystrophin-deficient muscles. These observations may be related to the resistance to nondepolarizing muscle relaxants and the high sensitivity to depolarizing agents reported in DMD patients.
Keywords nicotinic acetylcholine receptor
upregulation
dystrophin
muscular dystrophy
mdx mouse
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Date 2008-12-01
Published in Muscle & Nerve. Hoboken: John Wiley & Sons Inc, v. 38, n. 6, p. 1585-1594, 2008.
ISSN 0148-639X (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 1585-1594
Origin http://dx.doi.org/10.1002/mus.21183
Access rights Closed access
Type Article
Web of Science ID WOS:000261421100006
URI http://repositorio.unifesp.br/handle/11600/31060

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