Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024591 (
malignant hyperthermia
)
2,353
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Store-operated Ca
2+
entry (SOCE) is a Ca
2+
entry mechanism activated by depletion of intracellular Ca
2+
stores. In skeletal muscle, SOCE is mediated by an interaction between stromal-interacting molecule-1 (STIM1), the Ca
2+
sensor of the sarcoplasmic reticulum, and
ORAI1
, the Ca
2+
-release-activated-Ca
2+
(CRAC) channel located in the transverse tubule membrane. This review focuses on the molecular mechanisms and physiological role of SOCE in skeletal muscle, as well as how alterations in STIM1/
ORAI1
-mediated SOCE contribute to muscle disease. Recent evidence indicates that SOCE plays an important role in both muscle development/growth and fatigue. The importance of SOCE in muscle is further underscored by the discovery that loss- and gain-of-function mutations in STIM1 and
ORAI1
result in an eclectic array of disorders with clinical myopathy as central defining component. Despite differences in clinical phenotype, all STIM1/
ORAI1
gain-of-function mutations-linked myopathies are characterized by the abnormal accumulation of intracellular membranes, known as tubular aggregates. Finally, dysfunctional STIM1/
ORAI1
-mediated SOCE also contributes to the pathogenesis of muscular dystrophy,
malignant hyperthermia
, and sarcopenia. The picture to emerge is that tight regulation of STIM1/
ORAI1
-dependent Ca
2+
signaling is critical for optimal skeletal muscle development/function such that either aberrant increases or decreases in SOCE activity result in muscle dysfunction.
...
PMID:Role of STIM1/ORAI1-mediated store-operated Ca
2+
entry in skeletal muscle physiology and disease. 3041 8
