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 sk eletal muscle, has been identified to play roles in the formation of precis e junctional membrane structures important for efficient signal conversion in excitation-contraction (E-C) coupling. We carried out several experiment s 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 contracti le properties of three muscles types, extensor digitorum longus (EDL) (fast -twitch muscle), soleus (SOL) (slow-twitch muscle), and diaphragm (DPH) (mi xed-fiber muscle), isolated from mice lacking the MG29 gene and wild-type m ice prior to and after fatigue. Our results indicate that the mutant EDL an d SOL muscles, but not DPH, are more susceptible to fatigue than the wild-t ype muscles. The mutant muscles not only fatigued to a greater extent but a lso recovered significantly less than the wild-type muscles. Following fati gue, the mutant EDL and SOL muscles produced lower twitch forces than the w ild-type muscles; in addition, fatiguing produced a downward shift in the f orce-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 hom eostasis.