Volume 14, No 5, Oct 2004

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 14 Issue 5, October 2004: 373-378

ORIGINAL ARTICLES

Defective maintenance of intracellular Ca²⁺ homeostasis is linked to increased muscle fatigability in the MG29 null mice

Marco A. P. Brotto^1*, Ramakrishnan Y. Nagaraj¹, Leticia S. Brotto¹, Hiroshi Takeshima³,Jianjie Ma¹, Thomas M. Nosek²

¹Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA;
²Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA;
³Department of Biochemistry, Graduate School of Medicine,Tohoku University 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan Correspondence: Marco A. P. Brotto(brottoma@umdnj.edu)

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.

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