Increased expression of acetylcholine receptors in the diaphragm muscle of mdx mice.

Autor: Ghedini, Paulo C., Viel, Tânia A., Honda, Luciana, Avellar, Maria Christina W., Godinho, Rosely O., Lima-Landman, Maria Teresa R., Lapa, Antônio J., Souccar, Caden
Zdroj: Muscle & Nerve; Dec2008, Vol. 38 Issue 6, p1585-1594, 10p
Abstrakt: 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 [125I]-α-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 α1, γ, α7, and β2, but not the ϵ 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. Muscle Nerve 38: 1585-1594, 2008 [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index