IP3Rs (inositol 1,4,5-trisphosphate receptors) are expressed in the membranes of non-mitochondrial organelles in most animal cells, but their presence and role within the plasma membrane are unclear. Whole-cell patch–clamp recording from DT40 cells expressing native or mutated IP3Rs has established that each cell expresses just two or three functional IP3Rs in its plasma membrane. Only approx. 50% of the Ca2+ entry evoked by stimulation of the B-cell receptor is mediated by store-operated Ca2+ entry, the remainder appears to be carried by the IP3Rs expressed in the plasma membrane. Ca2+ entering the cell via just two large-conductance IP3Rs is likely to have very different functional consequences from the comparable amount of Ca2+ that enters through the several thousand low-conductance store-operated channels.