Store-operated Ca2+ entry (SOCE) is activated in response to a reduction of [Ca2+] in the ER and generates local and global [Ca2+]i signals that regulate a wide variety of cellular functions.Two types of channels have been associated with SOCE, CRAC channels and SOC channels.We have previously provided extensive data to demonstrate that TRPC1 is a critical component of SOC channels and SOCE salivary gland ceils.Further, salivary gland acinar cells from TRPC1-/-mice display reduced SOCE and SOC channel activity which account for loss of sustained Kca activation and, consequently, salivary fluid secretion.Orail is the pore-forming subunit of the CRAC channel while STIM1 is an ER Ca2+ binding protein that is the primary regulator of SOCE.While a major contribution of Orail to SOCE in these cells is that it regulates TRPC1, the exact contribution of Orail to Ca2+ signals and cell function is not yet known.Our recent studies have revealed that local Ca2+ entry mediated by Orail determines plasma membrane insertion of TRPC1 while STIM1 controls its gating.Thus, Orail and STIM1 not only determine Ca2+ signals generated by CRAC channels but by regulating TRPC1 channel activity rapidly modulate [Ca2+]i and thus significantly impact specific cellular functions in salivary gland acini.We have now resolved the distinct Ca2+ signals contributed by TRPC1-SOC and Orail-CRAC channels in response to agonist stimulation.The possible implications of this in regulation of gene expression and other cell function will be discussed.