IP(3) receptor subtype-dependent activation of store-operated calcium entry through I(CRAC).

The store-operated, calcium release-activated calcium current I(CRAC) is activated by the depletion of inositol 1,4,5-trisphosphate (IP(3))-sensitive stores. The significantly different dose-response relationships of IP(3)-mediated Ca(2+) 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 IP(3) receptor (IP(3)R) genes and most cells express at least two subtypes, but the functional relevance of various IP(3)R subtypes with respect to store-operated Ca(2+) entry is completely unknown. We here demonstrate in avian B cells (chicken DT40) that IP(3)R type II and type III participate in IP(3)-induced activation of I(CRAC), but IP(3)R type I does not. This suggests that the expression pattern of IP(3)R contributes to the formation of specialized CRAC stores in B cells.