title: Emerging roles for native Orai Ca2+ channels in cardiovascular disease.
abstract: Orai proteins form highly calcium (Ca(2+))-selective channels located in the plasma membrane of both nonexcitable and excitable cells, where they make important contributions to many cellular processes. The well-characterized Ca(2+) release-activated Ca(2+) current is mediated by Orai1 multimers and is activated, upon depletion of inositol 1,4,5-trisphosphate-sensitive stores, by direct interaction of Orai1 with the endoplasmic reticulum Ca(2+) sensor, stromal interaction molecule 1 (STIM1). This pathway is known as capacitative Ca(2+) entry or store-operated Ca(2+) entry. While most investigations have focused on STIM1 and Orai1 in their store-dependent mode, emerging evidence suggests that Orai1 and Orai3 heteromultimeric channels can form store-independent Ca(2+)-selective channels. The role of store-dependent and store-independent channels in excitation-transcription coupling and the pathological remodeling of the cardiovascular system are beginning to come forth. Recent evidence suggests that STIM/Orai-generated Ca(2+) signaling couples to gene transcription and subsequent phenotypic changes associated with the processes of cardiac and vascular remodeling. This short review will explore the contributions of native Orai channels to heart and vessel physiology and their role in cardiovascular diseases.
authors.affiliation: Nanobioscience Constellation, The College of Nanoscale Science and Engineering, University at Albany-State University of New York, Albany, NY, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Ruhle
authors.forename: Mohamed
authors.initials: M
authors.lastname: Trebak
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D020125:Mutation, Missense; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D000071740:ORAI1 Protein; D014661:Vasoconstriction
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human
keywords: Ca(2+) signaling; Cardiovascular disease; Endothelial cells; Orai1; Orai3; Store-independent Ca(2+) entry; Store-operated Ca(2+) entry; Stromal interaction molecule 1; Vascular smooth muscle cells
references.citation: Physiol Genomics. 2007 Feb 12;28(3):273-83
references.pmid: 16985003
references.citation: Nature. 2011 May 19;473(7347):298-307
references.pmid: 21593862
references.citation: Cardiovasc Res. 2005 Feb 15;65(3):581-6
references.pmid: 15664384
references.citation: Mol Cell Biol. 2008 Sep;28(17):5209-22
references.pmid: 18591248
references.citation: J Thromb Haemost. 2005 Jul;3(7):1392-406
references.pmid: 15892866
references.citation: J Physiol. 2011 Nov 15;589(Pt 22):5337-8
references.pmid: 22086246
references.citation: Circ Res. 2011 May 13;108(10):1190-8
references.pmid: 21441136
references.citation: Nat Med. 1999 Apr;5(4):434-8
references.pmid: 10202935
references.citation: Stem Cells. 2011 Nov;29(11):1898-907
references.pmid: 21905169
references.citation: Nature. 2006 Sep 14;443(7108):226-9
references.pmid: 16921385
references.citation: J Membr Biol. 1999 Mar 1;168(1):9-17
references.pmid: 10051685
references.citation: J Physiol. 2009 Sep 1;587(Pt 17):4181-97
references.pmid: 19622606
references.citation: Cell Calcium. 2004 Jun;35(6):643-57
references.pmid: 15110154
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15495-500
references.pmid: 19706428
references.citation: Circ Res. 2007 Feb 2;100(2):158-73
references.pmid: 17272818
references.citation: Biochem Biophys Res Commun. 2010 Jul 23;398(2):315-20
references.pmid: 20599714
references.citation: Nat Immunol. 2008 Jan;9(1):89-96
references.pmid: 18059270
references.citation: Pflugers Arch. 2012 Nov;464(5):481-92
references.pmid: 23014880
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4896-901
references.pmid: 20194792
references.citation: J Physiol. 2009 Jul 1;587(Pt 13):3101-11
references.pmid: 19403601
references.citation: Science. 1997 Feb 14;275(5302):964-7
references.pmid: 9020076
references.citation: Respir Res. 2009 Dec 11;10:123
references.pmid: 20003325
references.citation: Circ Res. 2011 Aug 19;109(5):534-42
references.pmid: 21737791
references.citation: Nat Rev Drug Discov. 2010 May;9(5):399-410
references.pmid: 20395953
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11406-11
references.pmid: 19549843
references.citation: Am J Physiol Cell Physiol. 2008 Sep;295(3):C779-90
references.pmid: 18596214
references.citation: Pflugers Arch. 2010 Oct;460(5):813-23
references.pmid: 20577885
references.citation: Am J Physiol Cell Physiol. 2012 Jan 15;302(2):C405-11
references.pmid: 22031597
references.citation: J Biol Chem. 2002 Apr 19;277(16):14266-73
references.pmid: 11827959
references.citation: Am J Physiol Cell Physiol. 2010 May;298(5):C993-1005
references.pmid: 20107038
references.citation: Circ Res. 2008 Nov 21;103(11):1289-99
references.pmid: 18845811
references.citation: Annu Rev Physiol. 2002;64:749-74
references.pmid: 11826287
references.citation: J Clin Invest. 1992 Oct;90(4):1614-21
references.pmid: 1328304
references.citation: Nature. 2012 Jan 25;482(7384):241-5
references.pmid: 22278058
references.citation: J Cell Biol. 2010 Aug 9;190(3):391-405
references.pmid: 20679432
references.citation: Tohoku J Exp Med. 2008 Aug;215(4):299-306
references.pmid: 18679003
references.citation: Am J Physiol Heart Circ Physiol. 2008 Dec;295(6):H2466-74
references.pmid: 18952717
references.citation: J Allergy Clin Immunol. 2009 Dec;124(6):1311-1318.e7
references.pmid: 20004786
references.citation: Circulation. 2008 Sep 30;118(14):1486-95
references.pmid: 18824655
references.citation: J Biol Chem. 2006 Aug 25;281(34):24979-90
references.pmid: 16807233
references.citation: Microcirculation. 2013 May;20(4):330-6
references.pmid: 23312019
references.citation: Nat Rev Mol Cell Biol. 2012 Sep;13(9):549-65
references.pmid: 22914293
references.citation: Vascul Pharmacol. 2010 Jan-Feb;52(1-2):55-62
references.pmid: 19951743
references.citation: Science. 2012 Dec 7;338(6112):1308-13
references.pmid: 23180775
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22516-21
references.pmid: 20018736
references.citation: Biochem Biophys Res Commun. 2009 Nov 6;389(1):172-6
references.pmid: 19715666
references.citation: Circ Res. 2012 Oct 12;111(9):1166-75
references.pmid: 22896585
references.citation: FASEB J. 1997 Nov;11(13):1119-26
references.pmid: 9367346
references.citation: Circulation. 2011 Aug 16;124(7):796-805
references.pmid: 21810664
references.citation: Am J Physiol Cell Physiol. 2010 Nov;299(5):C1079-90
references.pmid: 20739625
references.citation: FASEB J. 2002 Nov;16(13):1805-7
references.pmid: 12354692
references.citation: Cell. 2007 Dec 28;131(7):1327-39
references.pmid: 18160041
references.citation: J Biol Chem. 2000 Mar 31;275(13):9114-9
references.pmid: 10734044
references.citation: J Biol Chem. 2012 Feb 17;287(8):5917-27
references.pmid: 22203682
references.citation: J Physiol. 2008 Jan 1;586(1):185-95
references.pmid: 17991693
references.citation: Science. 2006 May 26;312(5777):1220-3
references.pmid: 16645049
references.citation: Nat Rev Mol Cell Biol. 2006 Aug;7(8):589-600
references.pmid: 16936699
references.citation: Nature. 2006 May 11;441(7090):179-85
references.pmid: 16582901
references.citation: Nat Cell Biol. 2008 Jun;10(6):688-97
references.pmid: 18488020
references.citation: J Cell Sci. 2012 Jan 15;125(Pt 2):287-94
references.pmid: 22302996
references.citation: Am J Physiol Heart Circ Physiol. 2012 Apr 15;302(8):H1546-62
references.pmid: 22245772
references.citation: Immunol Rev. 2009 Sep;231(1):189-209
references.pmid: 19754898
references.citation: PLoS One. 2012;7(9):e42541
references.pmid: 23049731
references.citation: J Physiol. 2001 May 15;533(Pt 1):185-99
references.pmid: 11351027
references.citation: J Cell Sci. 2000 Feb;113 ( Pt 4):653-62
references.pmid: 10652258
references.citation: Cell Calcium. 2002 Feb;31(2):89-96
references.pmid: 11969249
references.citation: J Biol Chem. 2001 Mar 16;276(11):7782-90
references.pmid: 11113149
references.citation: N Engl J Med. 2009 May 7;360(19):1971-80
references.pmid: 19420366
references.citation: Circ Res. 2013 Mar 29;112(7):1013-25
references.pmid: 23349245
references.citation: J Clin Invest. 2013 Feb;123(2):887-902
references.pmid: 23348743
references.citation: Blood. 2003 May 15;101(10):3765-77
references.pmid: 12543869
references.citation: Pflugers Arch. 1998 Jun;436(1):69-74
references.pmid: 9560448
references.citation: J Cell Biochem. 2009 Oct 1;108(2):499-507
references.pmid: 19626660
references.citation: J Mol Cell Cardiol. 2010 Jun;48(6):1329-34
references.pmid: 20138887
references.citation: Growth Factors. 2001;19(1):35-48
references.pmid: 11678208
references.citation: Cell. 2009 Mar 6;136(5):876-90
references.pmid: 19249086
references.citation: J Mol Cell Cardiol. 2011 Mar;50(3):460-70
references.pmid: 21111744
references.citation: N Engl J Med. 2008 Mar 27;358(13):1370-80
references.pmid: 18367740
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9357-62
references.pmid: 16751269
references.citation: Am J Physiol Cell Physiol. 2011 Apr;300(4):C919-26
references.pmid: 21270296
references.citation: J Cell Biol. 2005 Sep 26;170(7):1079-90
references.pmid: 16186254
references.citation: J Clin Invest. 2006 Dec;116(12):3114-26
references.pmid: 17099778
references.citation: Cardiovasc Res. 2009 Mar 1;81(4):660-8
references.pmid: 19052075
references.citation: Nat Cell Biol. 2009 Mar;11(3):337-43
references.pmid: 19182790
references.citation: J Biol Chem. 2010 Jun 18;285(25):19173-83
references.pmid: 20395295
references.citation: Cell. 1998 Apr 17;93(2):215-28
references.pmid: 9568714
references.citation: Int Rev Cytol. 1996;169:183-265
references.pmid: 8843655
references.citation: J Physiol. 2008 Jan 15;586(2):419-25
references.pmid: 18006576
references.citation: J Mol Cell Cardiol. 2012 Jan;52(1):62-73
references.pmid: 22064325
references.citation: Circ Res. 2007 Nov 26;101(11):1194-203
references.pmid: 17885217
references.citation: J Clin Invest. 2007 May;117(5):1344-53
references.pmid: 17431507
references.citation: Front Biosci (Schol Ed). 2013 Jan 01;5:766-73
references.pmid: 23277085
references.citation: Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H1124-32
references.pmid: 14630640
references.citation: Curr Biol. 2007 May 1;17(9):794-800
references.pmid: 17442569
references.citation: Nature. 2008 Nov 6;456(7218):116-20
references.pmid: 18820677
references.citation: Hypertension. 2009 Feb;53(2):409-16
references.pmid: 19075091
references.citation: Cell Calcium. 2004 Jun;35(6):583-9
references.pmid: 15110148
references.citation: Biochem Biophys Res Commun. 2011 Dec 9;416(1-2):45-50
references.pmid: 22079292
references.citation: Cancer Cell. 2002 Apr;1(3):247-55
references.pmid: 12086861
references.citation: Pflugers Arch. 2008 Aug;456(5):769-85
references.pmid: 18365243
references.citation: J Clin Invest. 2006 Mar;116(3):675-82
references.pmid: 16511602
references.citation: Pulm Circ. 2011 Winter;1(1):84-94
references.pmid: 21709766
references.citation: J Biol Chem. 2007 Jun 1;282(22):16232-43
references.pmid: 17293345
references.citation: J Pharm Pharmacol. 1999 Jul;51(7):831-40
references.pmid: 10467959
references.citation: Ann N Y Acad Sci. 2011 Nov;1238:74-90
references.pmid: 22129055
references.citation: Cardiovasc Res. 2012 Jul 15;95(2):156-64
references.pmid: 22406749
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14687-92
references.pmid: 19706554
references.citation: Nature. 2002 Jan 10;415(6868):198-205
references.pmid: 11805843
references.citation: Mol Ther. 2009 Mar;17(3):455-62
references.pmid: 19107116
references.citation: J Physiol. 2012 Jan 15;590(2):241-57
references.pmid: 22041188
references.citation: Nat Med. 2002 Nov;8(11):1249-56
references.pmid: 12411952
references.citation: Science. 2010 Oct 1;330(6000):105-9
references.pmid: 20929813
references.citation: Stem Cells Dev. 2010 Dec;19(12):1967-81
references.pmid: 20677912
references.citation: Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):27-36
references.pmid: 17095716
references.citation: Nat Rev Cancer. 2002 Nov;2(11):826-35
references.pmid: 12415253
references.citation: FASEB J. 2009 Aug;23(8):2425-37
references.pmid: 19364762
references.citation: J Gen Physiol. 2002 May;119(5):487-507
references.pmid: 11981025
references.citation: Exp Biol Med (Maywood). 2010 Mar;235(3):317-25
references.pmid: 20404049
references.citation: J Physiol. 2012 Sep 1;590(17):4201-8
references.pmid: 22641780
references.citation: J Physiol. 2007 Mar 15;579(Pt 3):703-15
references.pmid: 17158173
references.citation: Nature. 2006 Sep 14;443(7108):230-3
references.pmid: 16921383