Skeletal muscle fiber degeneration in mdx mice induced by electrical stimulation.
We present an in vitro model in which mouse skeletal muscle fibers undergo degeneration by increasing the current strength of tetanic stimulation. To understand the mechanisms of muscle fiber necrosis in Duchenne muscular dystrophy patients, the process of fiber degeneration was compared between mdx and control mice. The process consisted of four steps, beginning with muscle fiber contraction and extending to onset of myofibril disruption. The four processes were not observed in fibers in Krebs-HEPES (-Ca2+) buffer, nor in the presence of L-type Ca2+ channel blockers. These results suggest that this degenerative phenomenon is regulated by intracellular Ca2+, which moved into fibers mainly through voltage-dependent L-type Ca2+ channels. With the exception of myofibril disruption, mdx mice also exhibited the three other steps, but at a significantly lower current strength than in the fibers in the control mice. We postulate that excess Ca2+ flux occurs in fibers, mainly through abnormal L-type Ca2+ channels, and that the excessively accumulated calcium results in premature degeneration of the fibers by tetanic contraction. This study would provide a clue to investigate and prevent the degeneration processes in Duchenne muscular dystrophy.
Yoshida
M
M
Department of Degenerative Neurological Disease, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Matsuzaki
T
T
Date
M
M
Wada
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism; D007478:Iontophoresis; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology / Q000503:physiopathology*
D002121:Calcium Channel Blockers; D002118:Calcium