Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release

Nat Commun. 2014 May 28;5:3916. doi: 10.1038/ncomms4916.


The versatility and universality of Ca(2+) signals stem from the breadth of their spatial and temporal dynamics. Spatially, Ca(2+) signalling is well studied in the microdomain scale, close to a Ca(2+) channel, and at the whole-cell level. However, little is known about how local Ca(2+) signals are regulated to specifically activate spatially distant effectors without a global Ca(2+) rise. Here we show that an intricate coupling between the inositol 1,4,5 trisphosphate (IP3) receptor, SERCA pump and store-operated Ca(2+) entry (SOCE) allows for efficient mid-range Ca(2+) signalling. Ca(2+) flowing through SOCE is taken up into the ER lumen by the SERCA pump, only to be re-released by IP3Rs to activate distal Ca(2+)-activated Cl(-) channels (CaCCs). This CaCC regulation contributes to setting the membrane potential of the cell. Hence functional coupling between SOCE, SERCA and IP3R limits local Ca(2+) diffusion and funnels Ca(2+) through the ER lumen to activate a spatially separate Ca(2+) effector.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Calcium Signaling* / drug effects
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism
  • Female
  • Green Fluorescent Proteins / metabolism
  • Heparin / pharmacology
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Ion Channel Gating / drug effects
  • Membrane Microdomains / drug effects
  • Membrane Potentials / drug effects
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism
  • Xenopus laevis


  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Green Fluorescent Proteins
  • Egtazic Acid
  • Inositol 1,4,5-Trisphosphate
  • Heparin
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium