Ca2+ entry through plasma membrane IP3 receptors.
Inositol 1,4,5-trisphosphate receptors (IP3Rs) release calcium ions, Ca2+, from intracellular stores, but their roles in mediating Ca2+ entry are unclear. IP3 stimulated opening of very few (1.9 +/- 0.2 per cell) Ca2+-permeable channels in whole-cell patch-clamp recording of DT40 chicken or mouse B cells. Activation of the B cell receptor (BCR) in perforated-patch recordings evoked the same response. IP3 failed to stimulate intracellular or plasma membrane (PM) channels in cells lacking IP3R. Expression of IP3R restored both responses. Mutations within the pore affected the conductances of IP3-activated PM and intracellular channels similarly. An impermeant pore mutant abolished BCR-evoked Ca2+ signals, and PM IP3Rs were undetectable. After introduction of an alpha-bungarotoxin binding site near the pore, PM IP3Rs were modulated by extracellular alpha-bungarotoxin. IP(3)Rs are unusual among endoplasmic reticulum proteins in being also functionally expressed at the PM, where very few IP3Rs contribute substantially to the Ca2+ entry evoked by the BCR.
Dellis
Olivier
O
Department of Pharmacology, Tennis Court Road, Cambridge, CB2 1PD, UK.
Dedos
Skarlatos G
SG
Tovey
Stephen C
SC
Taufiq-Ur-Rahman
Dubel
Stefan J
SJ
Taylor
Colin W
CW
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens; D004553:Electric Conductivity; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015640:Ion Channel Gating; D051379:Mice; D009685:Nuclear Envelope / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017354:Point Mutation; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D002038:Bungarotoxins; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011947:Receptors, Antigen, B-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium