Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β

Orai1, the first identified member of the Orai protein family, is ubiquitously expressed in the animal kingdom. Orai1 was initially characterized as the channel responsible for the store-operated calcium entry (SOCE), a major mechanism that allows cytosolic calcium concentration increments upon receptor-mediated IP(3) generation, which results in intracellular Ca(2+) store depletion. Furthermore, current evidence supports that abnormal Orai1 expression or function underlies several disorders. Orai1 is, together with STIM1, the key element of SOCE, conducting the Ca(2+) release-activated Ca(2+) (CRAC) current and, in association with TRPC1, the store-operated Ca(2+) (SOC) current. Additionally, Orai1 is involved in non-capacitative pathways, as the arachidonate-regulated or LTC4-regulated Ca(2+) channel (ARC/LRC), store-independent Ca(2+) influx activated by the secretory pathway Ca(2+)-ATPase (SPCA2) and the small conductance Ca(2+)-activated K(+) channel 3 (SK3). Furthermore, Orai1 possesses two variants, Orai1α and Orai1β, the latter lacking 63 amino acids in the N-terminus as compared to the full-length Orai1α form, which confers distinct features to each variant. Here, we review the current knowledge about the differences between Orai1α and Orai1β, the implications of the Ca(2+) signals triggered by each variant, and their downstream modulatory effect within the cell.