title: Activation of store-mediated calcium entry by secretion-like coupling between the inositol 1,4,5-trisphosphate receptor type II and human transient receptor potential (hTrp1) channels in human platelets.
abstract: Physical coupling between inositol 1,4,5-trisphosphate (IP(3)) receptors and transient receptor potential (Trp) channels has been demonstrated in both transfected and normal cells as a candidate mechanism for the activation of store-mediated Ca(2+) entry (SMCE). We have investigated the properties of the coupling between the type II IP(3) receptor and naturally expressed human Trp1 (hTrp1) in human platelets. Treatment with xestospongin C, an inhibitor of IP(3) receptor function, abolished SMCE and coupling between the IP(3) receptor and hTrp1. The coupling was activated by depletion of the intracellular Ca(2+) stores, and was reversed by refilling of the stores. We have also examined the role of actin filaments in the activation and maintenance of the coupling. Stabilization of the cortical actin network with jasplakinolide prevented the coupling, indicating that, as with secretion, the actin filaments at the cell periphery act as a negative clamp which prevents constitutive coupling. In addition, the actin cytoskeleton plays a positive role, since disruption of the actin network inhibited the coupling when the Ca(2+) stores were depleted. These results provide strong evidence for the activation of SMCE by a secretion-like coupling mechanism involving a reversible association between IP(3) receptors and hTrp1 in normal human cells.
authors.affiliation: Department of Physiology, University of Cambridge, Downing St., Cambridge CB2 3EG, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Rosado
authors.forename: S O
authors.initials: SO
authors.lastname: Sage
mesh_terms: D000199:Actins / Q000378:metabolism; D001692:Biological Transport; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D010080:Oxazoles / Q000494:pharmacology; D011485:Protein Binding; D020239:Receptor Cross-Talk; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D050052:TRPC Cation Channels
chemical_list: D000199:Actins; D015220:Calcium Channels; D004791:Enzyme Inhibitors; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D010080:Oxazoles; D018160:Receptors, Cytoplasmic and Nuclear; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; C108644:xestospongin A; D015638:Cytochalasin D; D002118:Calcium