Counting Functional Inositol 1,4,5-Trisphosphate Receptors into the Plasma Membrane*

Abstract

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 B lymphocytes and a cell line derived from them (DT40 cells), very few functional IP₃R(∼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 ∼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.