Coupling between inositol 1,4,5-trisphosphate receptors and human transient receptor potential channel 1 when intracellular Ca2+ stores are depleted.
In the present study we have investigated the role of inositol 1,4, 5-trisphosphate (IP(3)), functional IP(3) receptors (IP(3)Rs) and the human homologue of the Drosophila transient receptor potential (Trp) channel, human Trp1 (hTrp1), in store-mediated Ca(2+) entry (SMCE) in human platelets. Inhibition of IP(3) recycling using Li(+), or the inhibition of IP(3)Rs using xestospongin C, both resulted in the inhibition of SMCE activation following Ca(2+) store depletion using thapsigargin. Co-immunoprecipitation experiments indicated that endogenously expressed hTrp1 couples with IP(3)R type II, but not types I or III, in platelets with depleted intracellular Ca(2+) stores, but not in control, undepleted cells. These results provide strong evidence for the activation of SMCE by conformational coupling involving de novo association between IP(3)Rs and a plasma membrane channel in normal human cells.
Rosado
J A
JA
Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, U.K.
Sage
S O
SO
D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D015220:Calcium Channels; D005656:Fungal Proteins; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D002118:Calcium