Defective maintenance of intracellular Ca2+ homeostasis is linked to increased muscle fatigability in the MG29 null mice.
Mitsugumin 29 (MG29) is a transmembrane protein that is normally found in the triad junction of skeletal muscle. Our previous studies have shown that targeted deletion of mg29 from the skeletal muscle resulted in abnormality of the triad junction structure, and also increased susceptibility to muscle fatigue. To elucidate the basis of these effects, we investigated the properties of Ca2+-uptake and -release in toxin-skinned Extensor Digitorium Longus (EDL) muscle fibers from control and mg29 knockout mice. Compared with the control muscle, submaximal Ca2+-uptake into the sarcoplasmic reticulum (SR) was slower and the storage of Ca2+ inside the SR was less in the mutant muscle, due to increased leakage process of Ca2+ movement across the SR. The leakage pathway is associated with the increased sensitivity of Ca2+/caffeine -induced Ca2+ release to myoplasmic Ca2+. Therefore, the increased fatigability of mutant EDL muscles can result from a combination of a slowing of Ca2+ uptake, modification of Ca2+-induced Ca2+ release (CICR), and a reduction in total SR Ca2+ content.
Brotto
Marco A P
MA
Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. brottoma@umdnj.edu
Nagaraj
Ramakrishnan Y
RY
Brotto
Leticia S
LS
Takeshima
Hiroshi
H
Ma
Jian Jie
JJ
Nosek
Thomas M
TM
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D018763:Muscle Fatigue / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology; D016708:Synaptophysin / Q000031:analogs & derivatives* / Q000235:genetics*; D013997:Time Factors
C111842:Mg29 protein, mouse; D009124:Muscle Proteins; D016708:Synaptophysin; D002110:Caffeine; D015759:Ionomycin; D002118:Calcium