Counting functional inositol 1,4,5-trisphosphate receptors into the plasma membrane

Inositol 1,4,5-trisphosphate receptors (IP3R) within the endoplasmic reticulum mediate release of Ca2+ from intracellular stores. Different channels usually mediate Ca2+ entry across the plasma membrane. In Blymphocytes and a cell line derived from them (DT40 cells), very few functional IP3R (similar to 2/cell) are invariably expressed in the plasma membrane, where they mediate about half the Ca2+ entry evoked by activation of the B-cell receptor. We show that cells reliably count similar to 2 functional IP3R into the plasma membrane even when their conductance and ability to bind IP3 are massively attenuated. We conclude that very small numbers of functional IP3R can be reliably counted into a specific membrane compartment in the absence of feedback signals from the active protein.