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

The store-operated, calcium release-activated calcium current I_CRAC 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 I_CRAC 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 I_CRAC, 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.