What role for store-operated Ca²⁺ entry in muscle?

Microcirculation. 2013 May;20(4):330-6. doi: 10.1111/micc.12042.


Store-operated Ca²⁺ entry (SOCE) is a receptor-regulated Ca²⁺ entry pathway that is both ubiquitous and evolutionarily conserved. SOCE is activated by depletion of intracellular Ca²⁺ stores through receptor-mediated production of inositol 1,4,5-trisphosphate (IP₃). The depletion of endoplasmic reticulum (ER) Ca²⁺ is sensed by stromal interaction molecule 1 (STIM1). On store depletion, STIM1 aggregates and moves to areas where the ER comes close to the plasma membrane (PM; within 25 nm) to interact with Orai1 channels and activate Ca²⁺ entry. Ca²⁺ entry through store-operated Ca²⁺ (SOC) channels, originally thought to mediate the replenishment of Ca²⁺ stores, participate in active downstream signaling by coupling to the activation of enzymes and transcription factors that control a wide variety of long-term cell functions such as proliferation, growth, and migration. SOCE has also been proposed to contribute to short-term cellular responses such as muscle contractility. While there are significant STIM1/Orai1 protein levels and SOCE activity in adult skeletal muscle, the precise role of SOCE in skeletal muscle contractility is not clear. The dependence on SOCE during cardiac and smooth muscle contractility is even less certain. Here, we will hypothesize on the contribution of SOCE in muscle and its potential role in contractility and signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium Signaling / physiology*
  • Cell Membrane / metabolism
  • Humans
  • Membrane Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Muscle, Smooth / metabolism*
  • Neoplasm Proteins / metabolism*
  • ORAI1 Protein
  • Stromal Interaction Molecule 1


  • Calcium Channels
  • Membrane Proteins
  • Neoplasm Proteins
  • ORAI1 Protein
  • ORAI1 protein, human
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • Calcium