Editors' ChoiceCalcium signaling

Milk needs Orai1

Sci. Signal.  19 May 2015:
Vol. 8, Issue 377, pp. ec127
DOI: 10.1126/scisignal.aac5307

Calcium (Ca2+) transport into milk by luminal epithelial cells in mammary alveoli during lactation involves the coordinated functions of Ca2+ channels, pumps, and Ca2+-sensing proteins. Expression of the gene encoding Orai1, a store-operated Ca2+ channel, increases in the mammary gland during lactation. Davis et al. found that the concentration of Ca2+ in milk from lactating Orai1-deficient (Orai1–/–) mice was half that in milk from wild-type (Orai1+/+) mice; however, total milk protein and maternal serum Ca2+ concentrations were indistinguishable. Histological analysis of mammary gland sections of Orai1+/+ and Orai1–/– mice showed that their structural development and secretory capacity were similar; however, alveoli from Orai1–/– mammary glands were more dilated and had increased staining of milk proteins trapped in the ducts and alveolar lumen. The structure and organization of myoepithelial cells, which generate the contractile force necessary to eject milk, were normal in Orai1–/– mice, and ionomycin-stimulated Ca2+ release from these cells was similar in both the wild-type and deficient mice. Oxytocin, a hormone that induces milk secretion, stimulated an initial Ca2+ spike in myoepithelial cells, which was followed by Ca2+ oscillations; however, these oscillations were dampened in Orai1–/– cells. Imaging of oxytocin-induced alveolar contractions in excised live mammary tissue showed that contractions were well coordinated in tissue from Orai1+/+ mice, but not that from Orai1–/– mice. These findings reveal a relationship between Orai1-mediated entry of Ca2+ into myoepithelial cells and alvelolar contraction, and suggest that Orai1 plays a role in both transporting Ca2+ into milk and ejecting milk through lactation.

F. M. Davis, A. Janoshazi, K. S. Janardhan, N. Steinckwich, D. M. D’Agostin, J. G. Petranka, P. N. Desai, S. J. Roberts-Thomson, G. S. Bird, D. K. Tucker, S. E. Fenton, S. Feske, G. R. Monteith, J. W. Putney Jr., Essential role of Orai1 store-operated calcium channels in lactation. Proc. Natl. Acad. Sci. U.S.A. 112, 5827–5832 (2015). [Abstract] [Full Text]