Increased susceptibility to fatigue of slow- and fast-twitch muscles from mice lacking the MG29 gene.
Mitsugumin 29 (MG29), a major protein component of the triad junction in skeletal muscle, has been identified to play roles in the formation of precise junctional membrane structures important for efficient signal conversion in excitation-contraction (E-C) coupling. We carried out several experiments to not only study the role of MG29 in normal muscle contraction but also to determine its role in muscle fatigue. We compared the in vitro contractile properties of three muscles types, extensor digitorum longus (EDL) (fast-twitch muscle), soleus (SOL) (slow-twitch muscle), and diaphragm (DPH) (mixed-fiber muscle), isolated from mice lacking the MG29 gene and wild-type mice prior to and after fatigue. Our results indicate that the mutant EDL and SOL muscles, but not DPH, are more susceptible to fatigue than the wild-type muscles. The mutant muscles not only fatigued to a greater extent but also recovered significantly less than the wild-type muscles. Following fatigue, the mutant EDL and SOL muscles produced lower twitch forces than the wild-type muscles; in addition, fatiguing produced a downward shift in the force-frequency relationship in the mutant mice compared with the wild-type controls. Our results indicate that fatiguing affects the E-C components of the mutant EDL and SOL muscles, and the effect of fatigue in these mutant muscles could be primarily due to an alteration in the intracellular Ca homeostasis.
Nagaraj
R Y
RY
Department of Physiology and Biophysics, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4963, USA.
Nosek
C M
CM
Brotto
M A
MA
Nishi
M
M
Takeshima
H
H
Nosek
T M
TM
Ma
J
J
D000818:Animals; D004558:Electric Stimulation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics; D018763:Muscle Fatigue / Q000235:genetics*; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism* / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism* / Q000502:physiology; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D016708:Synaptophysin / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000235:genetics*
C111842:Mg29 protein, mouse; D009124:Muscle Proteins; D016708:Synaptophysin