Coupling of the IP3 receptor/Ca2+ channel with Ca2+ storage proteins chromogranins A and B in secretory granules

The secretory granules of neuroendocrine cells, which function as an inositol (1,4,5)-trisphosphate sensitive intracellular Ca2+ store, contain both the inositol (I,4,5)-trisphosphate receptor/Ca2+ channel and the high-capacity low-affinity Ca2+ storage proteins, chromogranins A and B, ChromograninsA and B, which exist in similar to 2 mM range in the secretory granules, can bind 50-100 mol of Ca2+/mol with dissociation constants of 2-4 mM. These proteins interact directly with the inositol (1,4,5)-trisphosphate receptor/Ca2+ channel at the intragranular pH 5,5, not only changing the conformation of the inositol (1,4,5)-trisphosphate receptor/Ca2+ channel but also modulating the channel activity. Given the homo- and heterotetrameric existence of both the inositol (1,4,5)-trisphosphate receptor/Ca2+ channel and chromograninsA and a, these tetrameric proteins appear to interact, thus controlling the intracellular Ca2+ concentration.