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Science 313 (5784): 229-233

Copyright © 2006 by the American Association for the Advancement of Science

Ca2+ Entry Through Plasma Membrane IP3 Receptors

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 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. IP3Rs 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.

Department of Pharmacology, Tennis Court Road, Cambridge, CB2 1PD, UK.

* To whom correspondence should be addressed. E-mail: cwt1000{at}

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