High-throughput analyses of IP3 receptor behavior

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca(2+) channels. They are expressed in most animal cells and mediate release of Ca(2+) 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 Ca(2+) concentration, and these events are the fundamental units of Ca(2+) signaling. These openings allow Ca(2+) signals to be selectively delivered by individual channels to the specific Ca(2+) sensors that evoke cellular responses. Stimulation of IP3Rs by the Ca(2+) they release allows these tiny events to grow into much larger ones by recruitment of neighboring IP3Rs. Understanding how Ca(2+) effectively and specifically regulates so many cellular processes demands an understanding of the interplay between IP3 and Ca(2+) in controlling IP3R gating. Here, we briefly set the scene before introducing high-throughput methods that seek to address this issue.