High-Throughput Analyses of IP₃ Receptor Behavior

Abstract

Inositol 1,4,5-trisphosphate receptors (IP₃Rs) are intracellular Ca²⁺ channels. They are expressed in most animal cells and mediate release of Ca²⁺ from the endoplasmic reticulum (ER) in response to the many stimuli that evoke formation of inositol 1,4,5-trisphosphate (IP₃). The opening of individual IP₃Rs causes small, transient, local increases in cytosolic Ca²⁺ concentration, and these events are the fundamental units of Ca²⁺ signaling. These openings allow Ca²⁺ signals to be selectively delivered by individual channels to the specific Ca²⁺ sensors that evoke cellular responses. Stimulation of IP₃Rs by the Ca²⁺ they release allows these tiny events to grow into much larger ones by recruitment of neighboring IP₃Rs. Understanding how Ca²⁺ effectively and specifically regulates so many cellular processes demands an understanding of the interplay between IP₃ and Ca²⁺ in controlling IP₃R gating. Here, we briefly set the scene before introducing high-throughput methods that seek to address this issue.