Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes

EMBO J. 1999 Mar 1;18(5):1303-8. doi: 10.1093/emboj/18.5.1303.


Inositol 1,4,5-trisphosphate (IP3) plays a key role in Ca2+ signalling, which exhibits a variety of spatio-temporal patterns that control important cell functions. Multiple subtypes of IP3 receptors (IP3R-1, -2 and -3) are expressed in a tissue- and development-specific manner and form heterotetrameric channels through which stored Ca2+ is released, but the physiological significance of the differential expression of IP3R subtypes is not known. We have studied the Ca2+-signalling mechanism in genetically engineered B cells that express either a single or a combination of IP3R subtypes, and show that Ca2+-signalling patterns depend on the IP3R subtypes, which differ significantly in their response to agonists, i.e. IP3, Ca2+ and ATP. IP3R-2 is the most sensitive to IP3 and is required for the long lasting, regular Ca2+ oscillations that occur upon activation of B-cell receptors. IP3R-1 is highly sensitive to ATP and mediates less regular Ca2+ oscillations. IP3R-3 is the least sensitive to IP3 and Ca2+, and tends to generate monophasic Ca2+ transients. Furthermore, we show for the first time functional interactions between coexpressed subtypes. Our results demonstrate that differential expression of IP3R subtypes helps to encode IP3-mediated Ca2+ signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Antibodies / metabolism
  • B-Lymphocytes / metabolism*
  • Calcium / metabolism*
  • Calcium Channels / classification
  • Calcium Channels / metabolism*
  • Chickens
  • Fura-2
  • Gene Expression Regulation / genetics
  • Gene Targeting
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • Inositol 1,4,5-Trisphosphate Receptors
  • RNA, Messenger / metabolism
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Cytoplasmic and Nuclear / classification
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction
  • Tumor Cells, Cultured


  • Antibodies
  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • RNA, Messenger
  • Receptors, Antigen, B-Cell
  • Receptors, Cytoplasmic and Nuclear
  • Inositol 1,4,5-Trisphosphate
  • Adenosine Triphosphate
  • Calcium
  • Fura-2