Functional characterization of mammalian inositol 1,4,5-trisphosphate receptor isoforms

Biophys J. 2005 Feb;88(2):1046-55. doi: 10.1529/biophysj.104.049593. Epub 2004 Nov 8.


Inositol 1,4,5-trisphosphate receptors (InsP3R) play a key role in intracellular calcium (Ca2+) signaling. Three mammalian InsP3R isoforms--InsP3R type 1 (InsP3R1), InsP3R type 2 (InsP3R2), and InsP3R type 3 (InsP3R3) are expressed in mammals, but the functional differences between the three mammalian InsP3R isoforms are poorly understood. Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers and recorded with 50 mM Ba2+ as a current carrier. We found that: 1), for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS; 2), in optimal recording conditions the maximal single-channel open probability for all three mammalian InsP3R isoforms is in the range 30-40%; 3), in optimal recording conditions the mean open dwell time for all three mammalian InsP3R isoforms is 7-8 ms, the mean closed dwell time is approximately 10 ms; 4), InsP3R2 has the highest apparent affinity for InsP(3) (0.10 microM), followed by InsP3R1 (0.27 microM), and then by InsP3R3 (0.40 microM); 5), InsP3R1 has a high-affinity (0.13 mM) ATP modulatory site, InsP3R2 gating is ATP independent, and InsP3R3 has a low-affinity (2 mM) ATP modulatory site; 6), ATP modulates InsP3R1 gating in a noncooperative manner (n(Hill) = 1.3); 7), ATP modulates InsP3R3 gating in a highly cooperative manner (n(Hill) = 4.1). Obtained results provide novel information about functional properties of mammalian InsP3R isoforms.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / chemistry*
  • Animals
  • Electric Conductivity
  • Inositol 1,4,5-Trisphosphate / analysis
  • Inositol 1,4,5-Trisphosphate / chemistry*
  • Ion Channel Gating*
  • Kinetics
  • Lipid Bilayers / chemistry*
  • Membrane Potentials*
  • Protein Isoforms / analysis
  • Protein Isoforms / chemistry
  • Rats
  • Recombinant Proteins / analysis
  • Recombinant Proteins / chemistry
  • Structure-Activity Relationship


  • Lipid Bilayers
  • Protein Isoforms
  • Recombinant Proteins
  • Inositol 1,4,5-Trisphosphate
  • Adenosine Triphosphate