BMC cell biology

Assessment of ORAI1-mediated basal calcium influx in mammary epithelial cells.

PMID 24359162


The entry of calcium ions into mammary gland epithelial cells is one of the least well-understood processes in the transport of calcium into milk during lactation. The store-operated calcium entry channel ORAI1, has been suggested as a potential mechanism for the entry of Ca(2+) into mammary gland epithelial cells from the maternal blood supply during lactation. The down regulation of the canonical ORAI1 activator STIM1 during lactation suggests that other known ORAI activators such as STIM2 and SPCA2 may be important during lactation. Differentiation of HC11 mammary gland epithelial cells was associated with enhanced basal Ca(2+) influx. Silencing of Orai1 abolished this enhancement of Ca(2+) influx. Stim2 had a modest effect on Ca(2+) influx in this in vitro model of lactation, whereas Stim1 and Spca2 silencing had no effect. Despite pronounced increases in Spca2 mRNA during lactation there was no change in the generation of the alternative splice product generated by Mist1, which increases during lactation. These studies support the hypothesis that lactation is associated with a remodelling of Ca(2+) influx and this is associated with enhancement of basal Ca(2+) influx. This enhanced Ca(2+) influx appears to occur through the calcium channel Orai1.