TY - JOUR
T1 - Enhanced resistance to fatigue and altered calcium handling properties of sarcalumenin knockout mice
AU - Zhao, Xiaoli
AU - Yoshida, Morikatsu
AU - Brotto, Leticia
AU - Takeshima, Hiroshi
AU - Weisleder, Noah
AU - Hirata, Yutaka
AU - Nosek, Thomas M.
AU - Ma, Jianjie
AU - Brotto, Marco
PY - 2005/9/21
Y1 - 2005/9/21
N2 - Sarcalumenin is a Ca2+-binding protein located in the sarcoplasmic reticulum of striated muscle cells, the physiological function of which has not been fully determined yet. Using sarcalumenin knockout (sar -/-) mice, we showed that sar ablation altered store-operated Ca 2+ entry (SOCE) and enhanced muscle fatigue resistance. Sar -/- mice fatigued less with treadmill exercise, and intact isolated soleus and extensor digitorum longus muscles from sar-/- mice were more resistant to intermittent fatiguing stimulation than those from wild-type mice. Enhanced SOCE was observed in the sar-/- muscles. Biochemical analysis revealed that sar-/- muscles contained significantly elevated expression of mitsugumin 29 (MG29), a synaptophysin-related membrane protein located in the triad junction of skeletal muscle. Because the ablation of mg29 has been shown to cause increased fatigability and dysfunction of SOCE, the enhanced SOCE activity seen in sar-/- muscle may be correlated with the increased expression of MG29. Our data suggest that systemic ablation of sarcalumenin caused enhanced resistance to muscle fatigue by compensatory changes in Ca2+ regulatory proteins that effect SOCE.
AB - Sarcalumenin is a Ca2+-binding protein located in the sarcoplasmic reticulum of striated muscle cells, the physiological function of which has not been fully determined yet. Using sarcalumenin knockout (sar -/-) mice, we showed that sar ablation altered store-operated Ca 2+ entry (SOCE) and enhanced muscle fatigue resistance. Sar -/- mice fatigued less with treadmill exercise, and intact isolated soleus and extensor digitorum longus muscles from sar-/- mice were more resistant to intermittent fatiguing stimulation than those from wild-type mice. Enhanced SOCE was observed in the sar-/- muscles. Biochemical analysis revealed that sar-/- muscles contained significantly elevated expression of mitsugumin 29 (MG29), a synaptophysin-related membrane protein located in the triad junction of skeletal muscle. Because the ablation of mg29 has been shown to cause increased fatigability and dysfunction of SOCE, the enhanced SOCE activity seen in sar-/- muscle may be correlated with the increased expression of MG29. Our data suggest that systemic ablation of sarcalumenin caused enhanced resistance to muscle fatigue by compensatory changes in Ca2+ regulatory proteins that effect SOCE.
KW - Excitation-contraction coupling
KW - Mitsugumin 29
KW - Muscle fatigue
KW - Skeletal muscle
KW - Store-operated calcium channel
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U2 - 10.1152/physiolgenomics.00020.2005
DO - 10.1152/physiolgenomics.00020.2005
M3 - Article
C2 - 15998745
AN - SCOPUS:33645754718
SN - 1094-8341
VL - 23
SP - 72
EP - 78
JO - Physiological Genomics
JF - Physiological Genomics
IS - 1
ER -