title: S-Nitrosylation of cardiac ion channels.
abstract: Nitric oxide (NO) exerts ubiquitous signaling via posttranslational modification of cysteine residues, a reaction termed S-nitrosylation. Important substrates of S-nitrosylation that influence cardiac function include receptors, enzymes, ion channels, transcription factors, and structural proteins. Cardiac ion channels subserving excitation-contraction coupling are potentially regulated by S-nitrosylation. Specificity is achieved in part by spatial colocalization of ion channels with nitric oxide synthases (NOSs), enzymatic sources of NO in biologic systems, and by coupling of NOS activity to localized calcium/second messenger concentrations. Ion channels regulate cardiac excitability and contractility in millisecond timescales, raising the possibility that NO-related species modulate heart function on a beat-to-beat basis. This review focuses on recent advances in understanding of NO regulation of the cardiac action potential and of the calcium release channel ryanodine receptor, which is crucial for the generation of force. S-Nitrosylation signaling is disrupted in pathological states in which the redox state of the cell is dysregulated, including ischemia, heart failure, and atrial fibrillation.
authors.affiliation: Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Gonzalez
authors.forename: Adriana
authors.initials: A
authors.lastname: Treuer
authors.forename: Qi-An
authors.initials: QA
authors.lastname: Sun
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Stamler
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism; D056966:Excitation Contraction Coupling; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008133:Long QT Syndrome / Q000235:genetics / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D015538:Nitrosation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D007473:Ion Channels; D009569:Nitric Oxide
references.citation: J Neurosci. 2008 Sep 17;28(38):9463-72
references.pmid: 18799678
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2198-202
references.pmid: 18268335
references.citation: J Clin Invest. 2005 Mar;115(3):509-17
references.pmid: 15765132
references.citation: Neuron. 1998 Jan;20(1):115-24
references.pmid: 9459447
references.citation: Circulation. 2004 Oct 19;110(16):2368-75
references.pmid: 15466641
references.citation: Biochemistry. 2008 Dec 30;47(52):13985-90
references.pmid: 19053230
references.citation: J Mol Cell Cardiol. 2005 Dec;39(6):982-91
references.pmid: 16242147
references.citation: Cardiovasc Res. 2007 Jul 15;75(2):210-9
references.pmid: 17524376
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11158-62
references.pmid: 11562475
references.citation: J Biol Chem. 2003 Oct 31;278(44):42927-35
references.pmid: 12920114
references.citation: J Clin Invest. 2005 Aug;115(8):1990-9
references.pmid: 16075039
references.citation: J Am Coll Cardiol. 2007 Apr 24;49(16):1722-32
references.pmid: 17448375
references.citation: Neurosci Lett. 1999 Aug 27;271(3):159-62
references.pmid: 10507693
references.citation: Cell. 2008 Apr 4;133(1):53-65
references.pmid: 18394989
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4477-82
references.pmid: 18337493
references.citation: J Biol Chem. 2007 May 11;282(19):13977-83
references.pmid: 17376775
references.citation: Circ Res. 2004 Mar 5;94(4):478-86
references.pmid: 14699012
references.citation: Neuroscience. 2000;101(1):229-36
references.pmid: 11068151
references.citation: Nat Genet. 2006 Jun;38(6):644-51
references.pmid: 16648850
references.citation: Circ Res. 2008 Dec 5;103(12):1466-72
references.pmid: 19008475
references.citation: Biophys J. 2000 Jul;79(1):279-86
references.pmid: 10866954
references.citation: Circulation. 2009 Feb 24;119(7):940-51
references.pmid: 19204306
references.citation: J Biol Chem. 2009 Feb 27;284(9):6014-20
references.pmid: 19124472
references.citation: J Neurophysiol. 2002 Feb;87(2):761-75
references.pmid: 11826045
references.citation: J Physiol. 2002 Nov 1;544(3):883-96
references.pmid: 12411531
references.citation: Biochemistry. 2009 Feb 3;48(4):792-9
references.pmid: 19138101
references.citation: Nature. 2001 Mar 22;410(6827):490-4
references.pmid: 11260719
references.citation: Am J Physiol Heart Circ Physiol. 2008 Mar;294(3):H1473-80
references.pmid: 18203845
references.citation: Cardiovasc Res. 2008 Dec 1;80(3):375-84
references.pmid: 18678642
references.citation: Nat Med. 2009 Mar;15(3):325-30
references.pmid: 19198614
references.citation: Circulation. 2006 Oct 3;114(14):1531-44
references.pmid: 17015805
references.citation: Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7674-7
references.pmid: 1502182
references.citation: Science. 2008 May 23;320(5879):1050-4
references.pmid: 18497292
references.citation: Circ Res. 2007 Feb 16;100(3):e32-44
references.pmid: 17272813
references.citation: Science. 1998 Jan 9;279(5348):234-7
references.pmid: 9422697
references.citation: Nat Cell Biol. 2001 Feb;3(2):E46-9
references.pmid: 11175760
references.citation: Cell. 2000 Aug 18;102(4):499-509
references.pmid: 10966111
references.citation: Cardiovasc Res. 2008 Jan 15;77(2):380-6
references.pmid: 18006481
references.citation: Circ Res. 2007 Jan 5;100(1):96-104
references.pmid: 17138943
references.citation: Circ Res. 2007 Nov 26;101(11):1155-63
references.pmid: 17916778
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15944-8
references.pmid: 15486091
references.citation: Biochem J. 1998 Apr 15;331 ( Pt 2):659-68
references.pmid: 9531510
references.citation: Nat Cell Biol. 2001 Feb;3(2):193-7
references.pmid: 11175752
references.citation: Br J Pharmacol. 2004 Jun;142(3):567-75
references.pmid: 15148247
references.citation: Lancet. 2004 Apr 24;363(9418):1365-7
references.pmid: 15110495
references.citation: Trends Mol Med. 2003 Apr;9(4):160-8
references.pmid: 12727142
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6297-302
references.pmid: 19325130
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):461-6
references.pmid: 12524454
references.citation: Nitric Oxide. 2008 May;18(3):157-67
references.pmid: 18023373
references.citation: J Biol Chem. 1996 Aug 9;271(32):19180-5
references.pmid: 8702596
references.citation: J Physiol. 2007 May 1;580(Pt.3):951-60
references.pmid: 17331988
references.citation: Physiol Rev. 2005 Oct;85(4):1205-53
references.pmid: 16183911
references.citation: J Biol Chem. 1998 Apr 3;273(14):7828-34
references.pmid: 9525875
references.citation: J Cardiovasc Pharmacol. 2008 Oct;52(4):306-13
references.pmid: 18791466
references.citation: Circ Res. 2006 Feb 3;98(2):271-9
references.pmid: 16357304
references.citation: J Biol Chem. 2000 Sep 15;275(37):28810-5
references.pmid: 10833522
references.citation: Cell Calcium. 2005 Jan;37(1):87-96
references.pmid: 15541467
references.citation: Nat Cell Biol. 2001 Oct;3(10):867-73
references.pmid: 11584267
references.citation: Circulation. 2005 Dec 6;112(23):3633-43
references.pmid: 16330705
references.citation: J Clin Invest. 2005 May;115(5):1221-31
references.pmid: 15841206
references.citation: J Membr Biol. 2000 Feb 1;173(3):227-36
references.pmid: 10667918
references.citation: J Am Chem Soc. 2005 Nov 16;127(45):15815-23
references.pmid: 16277524
references.citation: J Cardiovasc Pharmacol. 2005 Jul;46(1):46-51
references.pmid: 15965354
references.citation: Circulation. 2008 Jul 29;118(5):476-81
references.pmid: 18625896
references.citation: J Am Coll Cardiol. 2003 Jun 18;41(12):2164-71
references.pmid: 12821241
references.citation: Circ Res. 1997 Nov;81(5):742-52
references.pmid: 9351448
references.citation: Nat Rev Mol Cell Biol. 2005 Feb;6(2):150-66
references.pmid: 15688001
references.citation: Biochem Biophys Res Commun. 1998 May 29;246(3):525-30
references.pmid: 9626329
references.citation: Life Sci. 1998;63(12):1023-35
references.pmid: 9749825
references.citation: Br J Clin Pharmacol. 2009 Jan;67(1):61-7
references.pmid: 19076153
references.citation: Biochemistry. 2007 Jul 17;46(28):8472-83
references.pmid: 17580965
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9355-60
references.pmid: 18591664
references.citation: J Exp Bot. 2006;57(8):1777-84
references.pmid: 16714306
references.citation: J Cardiovasc Pharmacol. 2000 Nov;36(5):656-68
references.pmid: 11065227
references.citation: Circ Res. 2005 Jan 7;96(1):64-72
references.pmid: 15569827
references.citation: Cell. 1996 Sep 6;86(5):719-29
references.pmid: 8797819
references.citation: Cell Calcium. 1997 Jan;21(1):19-29
references.pmid: 9056074
references.citation: Circulation. 2008 May 20;117(20):2626-36
references.pmid: 18474817
references.citation: J Gen Physiol. 1996 Oct;108(4):277-93
references.pmid: 8894977
references.citation: J Biol Chem. 2001 May 4;276(18):14797-803
references.pmid: 11278396
references.citation: Proc Natl Acad Sci U S A. 2006 May 9;103(19):7420-5
references.pmid: 16648260
references.citation: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8366-71
references.pmid: 16717191
references.citation: FEBS Lett. 1996 Feb 12;380(1-2):49-52
references.pmid: 8603745
references.citation: Nature. 2002 Jan 10;415(6868):213-8
references.pmid: 11805845
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20612-7
references.pmid: 18077344
references.citation: Circ Res. 2006 Feb 17;98(3):403-11
references.pmid: 16397145
references.citation: Antioxid Redox Signal. 2005 Jul-Aug;7(7-8):870-81
references.pmid: 15998242
references.citation: Circulation. 2004 Aug 17;110(7):856-61
references.pmid: 15289372
references.citation: Pharmacogenet Genomics. 2009 Apr;19(4):260-6
references.pmid: 19247217
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1012-7
references.pmid: 16418269
references.citation: Sci STKE. 2001 Jun 12;2001(86):pl1
references.pmid: 11752655
references.citation: Basic Res Cardiol. 2001 Apr;96(2):151-9
references.pmid: 11327333
references.citation: J Biol Chem. 2007 Sep 21;282(38):28063-73
references.pmid: 17656369
references.citation: Biophys J. 1998 Mar;74(3):1263-77
references.pmid: 9512024
references.citation: Nature. 2002 Jan 10;415(6868):198-205
references.pmid: 11805843
references.citation: Cardiovasc Res. 2006 Oct 1;72(1):80-9
references.pmid: 16876149
references.citation: Circulation. 2007 Jul 3;116(1):10-6
references.pmid: 17576865
references.citation: Biochim Biophys Acta. 1999 Sep 21;1451(2-3):271-87
references.pmid: 10556582
references.citation: Circulation. 2002 Nov 26;106(22):2854-8
references.pmid: 12451014
references.citation: J Biol Chem. 2002 Mar 22;277(12):9637-40
references.pmid: 11796706
references.citation: Nat Chem Biol. 2007 Dec;3(12):785-94
references.pmid: 17982448
references.citation: J Biol Chem. 1998 Mar 13;273(11):6041-5
references.pmid: 9497319
references.citation: Biophys J. 2003 Apr;84(4):2319-30
references.pmid: 12668440
references.citation: Neuron. 1998 May;20(5):1039-49
references.pmid: 9620707
references.citation: Neuron. 1997 May;18(5):691-6
references.pmid: 9182795
references.citation: Mol Pharmacol. 1999 Dec;56(6):1298-308
references.pmid: 10570058