title: Orai1 and Ca2+-independent phospholipase A2 are required for store-operated Icat-SOC current, Ca2+ entry, and proliferation of primary vascular smooth muscle cells.
abstract: Store-operated Ca(2+) entry (SOCE) is important for multiple functions of vascular smooth muscle cells (SMC), which, depending of their phenotype, can resemble excitable and nonexcitable cells. Similar to nonexcitable cells, Orai1 was found to mediate Ca(2+)-selective (CRAC-like) current and SOCE in dedifferentiated cultured SMC and smooth muscle-derived cell lines. However, the role of Orai1 in cation-selective store-operated channels (cat-SOC), which are responsible for SOCE in primary SMC, remains unclear. Here we focus on primary SMC, and assess the role of Orai1 and Ca(2+)-independent phospholipase A(2) (iPLA(2)β, or PLA2G6) in activation of cat-SOC current (I(cat-SOC)), SOCE, and SMC proliferation. Using molecular, electrophysiological, imaging, and functional approaches, we demonstrate that molecular knockdown of either Orai1 or iPLA(2)β leads to similar inhibition of the whole cell cat-SOC current and SOCE in primary aortic SMC and results in significant reduction in DNA synthesis and impairment of SMC proliferation. This is the first demonstration that Orai1 and iPLA(2)β are equally important for cat-SOC, SOCE, and proliferation of primary aortic SMC.
authors.affiliation: Ion Channel and Calcium Signaling Unit, Boston Univ. School of Medicine, Boston, MA 02118-2393, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gwozdz
authors.forename: Joanna
authors.initials: J
authors.lastname: Dutko-Gwozdz
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Bolotina
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D054522:Group VI Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D000071740:ORAI1 Protein; D018408:Patch-Clamp Techniques; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D051381:Rats
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; C532493:Orai1 protein, rat; D034741:RNA, Small Interfering; D054522:Group VI Phospholipases A2; C516476:Pla2g6 protein, mouse; D002118:Calcium
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