title: Stim, ORAI and TRPC channels in the control of calcium entry signals in smooth muscle.
abstract: Ca2+ entry signals are crucial in the control of smooth muscle contraction. Smooth muscle cells are unusual in containing plasma membrane (PM) Ca2+ entry channels that respond to voltage changes, receptor activation and Ca2+ store depletion. Activation of these channel subtypes is highly coordinated. The TRPC6 channel, widely expressed in most smooth muscle cell types, is largely non-selective to cations and is activated by diacylglycerol arising from receptor-induced phosholipase C activation. Receptor activation results largely in Na+ ion movement through TRPC6 channels, depolarization and subsequent activation of voltage-dependent L-type Ca2+ channels. The TRPC6 channels also appear to be activated by mechanical stretch, resulting again in depolarization and L-type Ca2+ channel activation. Such a coupling may be crucial in mediating the myogenic tone response in vascular smooth muscle. The emptying of stores mediated by inositol 1,4,5-trisphosphate receptors triggers the endoplasmic reticulum (ER) Ca2+ sensing protein stromal-interacting molecule (STIM) 1 to translocate into defined ER-PM junctional areas in which coupling occurs to Orai proteins, which serve as highly Ca2+-selective low-conductance Ca2+ entry channels. These ER-PM junctional domains may serve as crucial sites of interaction and integration between the function of store-operated, receptor-operated and voltage-operated Ca2+ channels. The STIM, Orai and TRPC channels represent highly promising new pharmacological targets through which such control may be induced.
authors.affiliation: Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Deng
authors.forename: Thamara
authors.initials: T
authors.lastname: Hewavitharana
authors.forename: Jonathan
authors.initials: J
authors.lastname: Soboloff
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gill
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000502:physiology; D009363:Neoplasm Proteins / Q000502:physiology*; D000071740:ORAI1 Protein; D011485:Protein Binding; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels / Q000378:metabolism / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; D002118:Calcium
references.citation: Circ Res. 2002 Feb 22;90(3):248-50
references.pmid: 11861411
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4040-5
references.pmid: 16537481
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2005 Apr;371(4):257-65
references.pmid: 15909153
references.citation: Cell Calcium. 2007 Aug;42(2):213-23
references.pmid: 17350680
references.citation: Science. 2006 Jul 14;313(5784):183-4
references.pmid: 16840689
references.citation: Circ Res. 2006 Apr 14;98(7):868-78
references.pmid: 16614312
references.citation: J Biol Chem. 2002 Mar 1;277(9):6915-22
references.pmid: 11741932
references.citation: Nature. 2006 Sep 14;443(7108):230-3
references.pmid: 16921383
references.citation: Sci STKE. 2004 Jul 20;2004(243):pe39
references.pmid: 15280581
references.citation: Nat Cell Biol. 2002 Nov;4(11):E263-72
references.pmid: 12415286
references.citation: J Physiol. 2004 Sep 15;559(Pt 3):685-706
references.pmid: 15272031
references.citation: Physiol Rev. 2005 Apr;85(2):757-810
references.pmid: 15788710
references.citation: Nature. 1999 Jan 21;397(6716):259-63
references.pmid: 9930701
references.citation: Nature. 2006 Sep 14;443(7108):226-9
references.pmid: 16921385
references.citation: Biochem Biophys Res Commun. 2007 Oct 5;361(4):934-40
references.pmid: 17689489
references.citation: Biochem J. 1995 Nov 15;312 ( Pt 1):1-11
references.pmid: 7492298
references.citation: Curr Biol. 2006 Jul 25;16(14):1465-70
references.pmid: 16860747
references.citation: Cell. 2007 Dec 14;131(6):1047-58
references.pmid: 18083096
references.citation: J Cell Sci. 2001 Jun;114(Pt 12):2223-9
references.pmid: 11493662
references.citation: Nat Cell Biol. 2006 Jul;8(7):771-3
references.pmid: 16733527
references.citation: Am J Respir Cell Mol Biol. 2008 Jun;38(6):744-9
references.pmid: 18239188
references.citation: Cell Calcium. 2007 Aug;42(2):173-82
references.pmid: 17602740
references.citation: Respir Res. 2006 Sep 20;7:119
references.pmid: 16987424
references.citation: J Physiol. 2000 Aug 15;527 Pt 1:139-48
references.pmid: 10944177
references.citation: Annu Rev Physiol. 2006;68:619-47
references.pmid: 16460286
references.citation: J Cell Biol. 2006 Sep 11;174(6):803-13
references.pmid: 16966422
references.citation: Curr Biol. 2006 Oct 24;16(20):2073-9
references.pmid: 16978865
references.citation: J Biol Chem. 2006 Aug 25;281(34):24979-90
references.pmid: 16807233
references.citation: Am J Physiol Cell Physiol. 2003 Feb;284(2):C316-30
references.pmid: 12529250
references.citation: Am J Physiol Cell Physiol. 2000 Feb;278(2):C235-56
references.pmid: 10666018
references.citation: Nature. 2004 Jul 8;430(6996):235-40
references.pmid: 15241420
references.citation: J Physiol. 2007 Aug 15;583(Pt 1):25-36
references.pmid: 17615095
references.citation: Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2055-61
references.pmid: 15604128
references.citation: Nature. 2006 May 11;441(7090):179-85
references.pmid: 16582901
references.citation: Science. 2006 May 26;312(5777):1220-3
references.pmid: 16645049
references.citation: J Gen Physiol. 2000 May;115(5):583-98
references.pmid: 10779316
references.citation: J Biol Chem. 2005 Dec 2;280(48):39786-94
references.pmid: 16204251
references.citation: J Physiol. 2001 Oct 1;536(Pt 1):3-19
references.pmid: 11579153
references.citation: Circ Res. 2001 Feb 16;88(3):325-32
references.pmid: 11179201
references.citation: J Biol Chem. 2006 Jul 28;281(30):20661-20665
references.pmid: 16766533
references.citation: Physiol Rev. 1997 Oct;77(4):901-30
references.pmid: 9354808
references.citation: J Biol Chem. 2006 Sep 22;281(38):28254-64
references.pmid: 16870612
references.citation: Novartis Found Symp. 2004;258:172-85; discussion 185-8, 263-6
references.pmid: 15104182
references.citation: FEBS Lett. 1990 Apr 9;263(1):5-9
references.pmid: 2185036
references.citation: J Biol Chem. 2006 Nov 24;281(47):35855-62
references.pmid: 17020874
references.citation: Nat Rev Mol Cell Biol. 2000 Oct;1(1):11-21
references.pmid: 11413485
references.citation: Sci STKE. 2004 Jul 20;2004(243):pe33
references.pmid: 15280575
references.citation: J Biol Chem. 2007 Mar 23;282(12):9105-16
references.pmid: 17224452
references.citation: Cell. 1999 Aug 20;98(4):487-99
references.pmid: 10481913
references.citation: Novartis Found Symp. 2004;258:103-18; discussion 118-22, 155-9, 263-6
references.pmid: 15104178
references.citation: J Biol Chem. 2003 Aug 1;278(31):29031-40
references.pmid: 12721302
references.citation: J Cell Biol. 2005 May 9;169(3):435-45
references.pmid: 15866891
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16586-91
references.pmid: 17056714
references.citation: Nat Genet. 2005 Jul;37(7):739-44
references.pmid: 15924139
references.citation: Curr Biol. 2005 Jul 12;15(13):1235-41
references.pmid: 16005298
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2895-900
references.pmid: 18287061
references.citation: Nat Cell Biol. 2006 Sep;8(9):1003-10
references.pmid: 16906149
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9357-62
references.pmid: 16751269
references.citation: Pflugers Arch. 2007 Dec;455(3):465-77
references.pmid: 17647013
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13861-6
references.pmid: 15358862
references.citation: Sci STKE. 2005 Feb 22;2005(272):re3
references.pmid: 15728426
references.citation: Physiol Rev. 1999 Apr;79(2):387-423
references.pmid: 10221985
references.citation: Nature. 2003 Dec 4;426(6966):517-24
references.pmid: 14654832
references.citation: Nat Rev Mol Cell Biol. 2003 Jul;4(7):517-29
references.pmid: 12838335
references.citation: J Physiol. 2003 Nov 1;552(Pt 3):789-95
references.pmid: 12972630
references.citation: Nature. 2005 Oct 6;437(7060):902-5
references.pmid: 16208375
references.citation: Mol Cell Biol. 2005 Aug;25(16):6980-9
references.pmid: 16055711
references.citation: Biochem Biophys Res Commun. 2004 Oct 1;322(4):1352-8
references.pmid: 15336983
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4682-7
references.pmid: 17360584
references.citation: Am J Physiol Cell Physiol. 2002 Feb;282(2):C347-59
references.pmid: 11788346
references.citation: Biochim Biophys Acta. 2006 Nov;1763(11):1161-8
references.pmid: 17084918
references.citation: Sci STKE. 2004 Jul 20;2004(243):pe35
references.pmid: 15280577