IP3 receptor subtype-dependent activation of store-operated calcium entry through ICRAC

The store-operated, calcium release-activated calcium current ICRAC is activated by the depletion of inositol 1,4,5-trisphosphate (IP3)-sensitive stores. The significantly different dose–response relationships of IP3-mediated Ca2+ release and CRAC channel activation indicate that ICRAC is activated by a functionally, and possibly physically, distinct sub-compartment of the endoplasmic reticulum (ER), the so-called CRAC store. Vertebrate genomes contain three IP3 receptor (IP3R) genes and most cells express at least two subtypes, but the functional relevance of various IP3R subtypes with respect to store-operated Ca2+ entry is completely unknown. We here demonstrate in avian B cells (chicken DT40) that IP3R type II and type III participate in IP3-induced activation of ICRAC, but IP3R type I does not. This suggests that the expression pattern of IP3R contributes to the formation of specialized CRAC stores in B cells.