title: Stretch-activated calcium channel protein TRPC1 is correlated with the different degrees of the dystrophic phenotype in mdx mice.
abstract: In Duchenne muscular dystrophy (DMD) and in the mdx mouse model of DMD, the lack of dystrophin is related to enhanced calcium influx and muscle degeneration. Stretch-activated channels (SACs) might be directly involved in the pathology of DMD, and transient receptor potential cation channels have been proposed as likely candidates of SACs. We investigated the levels of transient receptor potential canonical channel 1 (TRPC1) and the effects of streptomycin, a SAC blocker, in muscles showing different degrees of the dystrophic phenotype. Mdx mice (18 days old, n = 16) received daily intraperitoneal injections of streptomycin (182 mg/kg body wt) for 18 days, followed by removal of the diaphragm, sternomastoid (STN), biceps brachii, and tibialis anterior muscles. Control mdx mice (n = 37) were injected with saline. Western blot analysis showed higher levels of TRPC1 in diaphragm muscle compared with STN and limb muscles. Streptomycin reduced creatine kinase and prevented exercise-induced increases of total calcium and Evans blue dye uptake in diaphragm and in STN muscles. It is suggested that different levels of the stretch-activated calcium channel protein TRPC1 may contribute to the different degrees of the dystrophic phenotype seen in mdx mice. Early treatment designed to regulate the activity of these channels may ameliorate the progression of dystrophy in the most affected muscle, the diaphragm.
authors: Departamento de Anatomia, Biologia Celular, Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil. marques@unicamp.br
authors: Cíntia Yuri
authors: CY
authors: Matsumura
authors: Ana Paula Tiemi
authors: AP
authors: Taniguti
authors: Adriana
authors: A
authors: Pertille
authors: Humberto
authors: H
authors: Santo Neto
authors: Maria Julia
authors: MJ
authors: Marques
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D007473:Ion Channels / Q000502:physiology; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D011500:Protein Synthesis Inhibitors; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D013307:Streptomycin