Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The store-operated Ca2+ channel (SOC) located on the plasma membrane (PM) mediates capacitative entry of extracellular Ca2+ following depletion of intracellular Ca2+ stores in the endoplasmic or sarcoplasmic reticulum (ER/SR). It plays important roles in a variety of cell signaling processes, including proliferation, apoptosis, gene regulation and motility. In skeletal muscle, the L-type Ca2+ channel on the surface membrane has slow kinetics of activation in response to voltage stimulation, and therefore does not support entry of extracellular Ca2+. Recent studies have provided functional evidence for the existence of SOC in muscle cells. Severe dysfunction of SOC is identified in muscle cells lacking either ryanodine receptors located on the SR membrane, or mitsugumin 29 - a membrane protein located in the triad junction of skeletal muscle. These results indicate that SOC activation requires an intact interaction between PM and SR, and is linked to conformational changes of ryanodine receptors. The cumulative entry of Ca2+ through SOC not only provides the mechanism for refilling of intracellular Ca2+ stores, but may also add to the Ca2+ needed for muscle contraction under conditions of intensive exercise and fatigue. The proper coupling of PM with ER/SR, in the triad junction in skeletal muscle or dyad junction in cardiac muscle, is essential not only for the membrane excitation-induced intracellular Ca2+ release but also for the store depletion-initiated capacitative Ca2+ entry.
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PMID:Junctional membrane structure and store operated calcium entry in muscle cells. 1245 55

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 Ca2+ 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.
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PMID:Enhanced resistance to fatigue and altered calcium handling properties of sarcalumenin knockout mice. 1599 45