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Olivier Dellis,
Skarlatos G. Dedos,
Stephen C. Tovey,
Taufiq-Ur-Rahman,
Stefan J. Dubel,
Colin W. Taylor*
Abstract:
Inositol 1,4,5-trisphosphate receptors (IP3Rs) release calciumions, Ca2+, from intracellular stores, but their roles in mediatingCa2+ entry are unclear. IP3 stimulated opening of very few (1.9± 0.2 per cell) Ca2+-permeable channels in whole-cellpatch-clamp recording of DT40 chicken or mouse B cells. Activationof the B cell receptor (BCR) in perforated-patch recordingsevoked the same response. IP3 failed to stimulate intracellularor plasma membrane (PM) channels in cells lacking IP3R. Expressionof IP3R restored both responses. Mutations within the pore affectedthe conductances of IP3-activated PM and intracellular channelssimilarly. An impermeant pore mutant abolished BCR-evoked Ca2+signals, and PM IP3Rs were undetectable. After introductionof an -bungarotoxin binding site near the pore, PM IP3Rs weremodulated by extracellular -bungarotoxin. IP3Rs are unusualamong endoplasmic reticulum proteins in being also functionallyexpressed at the PM, where very few IP3Rs contribute substantiallyto the Ca2+ entry evoked by the BCR.
Department of Pharmacology, Tennis Court Road, Cambridge, CB2 1PD, UK.
* To whom correspondence should be addressed. E-mail: cwt1000{at}cam.ac.uk
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