Ca2+ signalling by IP3 receptors

Abstract

The Ca2+ signals evoked by inositol 1,4,5-trisphosphate (IP3) are built from elementary Ca2+release events involving progressive recruitment of IP3 receptors (IP3R), intracellular Ca2+ channels that are expressed in almost all animal cells. The smallest events (‘blips’) result from opening of single IP3R. Larger events (‘puffs’) reflect the near-synchronous opening of a small cluster of IP3R. These puffs become more frequent as the stimulus intensity increases and they eventually trigger regenerative Ca2+ waves that propagate across the cell. This hierarchical recruitment of IP3R is important in allowing Ca2+ signals to be delivered locally to specific target proteins or more globally to the entire cell. Co-regulation of IP3R by Ca2+ and IP3, the ability of a single IP3R rapidly to mediate a large efflux of Ca2+ from the endoplasmic reticulum, and the assembly of IP3R into clusters are key features that allow IP3R to propagate Ca2+ signals regeneratively. We review these properties of IP3R and the structural basis of IP3R behavior.