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Diltiazem and verapamil protect dystrophin‐deficient muscle fibers of MDX mice from degeneration: A potential role in calcium buffering and sarcolemmal stability
Author(s) -
Matsumura Cintia Yuri,
Pertille Adriana,
Albuquerque Tereza C.P.,
Santo Neto Humberto,
Marques Maria Julia
Publication year - 2009
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21188
Subject(s) - sarcolemma , diltiazem , verapamil , dystrophin , duchenne muscular dystrophy , medicine , endocrinology , calcium , creatine kinase , mdx mouse , sarcoplasm , chemistry , skeletal muscle
The lack of dystrophin in mdx mice and in Duchenne muscular dystrophy causes sarcolemmal breakdown and increased calcium influx followed by myonecrosis. We examined whether the calcium channel blockers diltiazem and verapamil protect dystrophic muscles from degeneration. Mdx mice received daily intraperitoneal injections of diltiazem or verapamil for 18 days, followed by removal of the sternomastoid, diaphragm, tibialis anterior, and cardiac muscles. Control mdx mice were injected with saline. Both drugs significantly decreased blood creatine kinase levels. Total calcium content was significantly higher in mdx muscles than in control C57Bl/10. Verapamil and diltiazem reduced total calcium content only in diaphragm and cardiac muscle. Histological analysis showed that diltiazem significantly attenuated myonecrosis in diaphragm. Immunoblots showed a significant increase of calsequestrin and β‐dystroglycan levels in some diltiazem‐ and verapamil‐treated muscles. Possible interactions of these drugs with the sarcoplasmic reticulum and sarcolemma may also contribute to the improvement of the dystrophic phenotype. Muscle Nerve 39: 167–176, 2009