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-trisph osphate (IP3), functional IF3 receptors (IP(3)Rs) and the human homologue o f the Drosophila transient receptor potential (Trp) channel, human Trp1 (hT rp1), in store-mediated Ca2+ entry (SMCE) in human platelets. Inhibition of IP3 recycling using Li+, or the inhibition of IP(3)Rs using xestospongin C , both resulted in the inhibition of SMCE activation following Ca2+ store d epletion using thapsigargin. Co-immunoprecipitation experiments indicated t hat endogenously expressed hTrp1 couples with IP3R type II, but not types I or III, in platelets with depleted intracellular Ca2+ stores, but not in c ontrol, undepleted cells. These results provide strong evidence for the act ivation of SMCE by conformational coupling involving de novo association be tween IP(3)Rs and a plasma membrane channel in normal human cells.