Ca 2+ Entry Through Plasma Membrane IP 3 Receptors

Abstract

Inositol 1,4,5-trisphosphate receptors (IP 3 Rs) release calcium ions, Ca 2+ , from intracellular stores, but their roles in mediating Ca 2+ entry are unclear. IP 3 stimulated opening of very few (1.9 ± 0.2 per cell) Ca 2+ -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. IP 3 failed to stimulate intracellular or plasma membrane (PM) channels in cells lacking IP 3 R. Expression of IP 3 R restored both responses. Mutations within the pore affected the conductances of IP 3 -activated PM and intracellular channels similarly. An impermeant pore mutant abolished BCR-evoked Ca 2+ signals, and PM IP 3 Rs were undetectable. After introduction of an α-bungarotoxin binding site near the pore, PM IP 3 Rs were modulated by extracellular α-bungarotoxin. IP 3 Rs are unusual among endoplasmic reticulum proteins in being also functionally expressed at the PM, where very few IP 3 Rs contribute substantially to the Ca 2+ entry evoked by the BCR.