The N-terminal domain of the IP3 receptor gates store-operated hTrp3 channels

Mol Cell. 1999 Sep;4(3):423-9. doi: 10.1016/s1097-2765(00)80344-5.


In the present work, we studied the interaction and effect of several IP3 receptor (IP3R) constructs on the gating of the store-operated (SOC) hTrp3 channel. Full-length IP3R coupled to silent hTrp3 channels in intact cells but did not activate them until stores were depleted of Ca2+. By contrast, constructs containing the IP3-binding domain activated silent hTrp3 channels in unstimulated cells and restored gating of hTrp3 by IP3 in excised plasma membrane patches. We conclude that the N-terminal domain of the IP3R functions as a gate and is sufficient for activation of SOCs. The sensing and transduction domains of the IP3R are required to maintain SOCs in an inactive state.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / metabolism*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ion Channel Gating*
  • Patch-Clamp Techniques
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Conformation
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Recombinant Proteins / metabolism
  • TRPC Cation Channels


  • Calcium Channels
  • ITPR1 protein, human
  • Inositol 1,4,5-Trisphosphate Receptors
  • Peptide Fragments
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Proteins
  • TRPC Cation Channels
  • transient receptor potential cation channel, subfamily C, member 1
  • Calcium