title: Mitochondria-derived superoxide and voltage-gated sodium channels in baroreceptor neurons from chronic heart-failure rats.
abstract: Our previous study has shown that chronic heart failure (CHF) reduces expression and activation of voltage-gated sodium (Na(v)) channels in baroreceptor neurons, which are involved in the blunted baroreceptor neuron excitability and contribute to the impairment of baroreflex in the CHF state. The present study examined the role of mitochondria-derived superoxide in the reduced Na(v) channel function in coronary artery ligation-induced CHF rats. CHF decreased the protein expression and activity of mitochondrial complex enzymes and manganese SOD (MnSOD) and elevated the mitochondria-derived superoxide level in the nodose neurons compared with those in sham nodose neurons. Adenoviral MnSOD (Ad.MnSOD) gene transfection (50 multiplicity of infection) into the nodose neurons normalized the MnSOD expression and reduced the elevation of mitochondrial superoxide in the nodose neurons from CHF rats. Ad.MnSOD also partially reversed the reduced protein expression and current density of the Na(v) channels and the suppressed cell excitability (the number of action potential and the current threshold for inducing action potential) in aortic baroreceptor neurons from CHF rats. Data from the present study indicate that mitochondrial dysfunction, including decreased protein expression and activity of mitochondrial complex enzymes and MnSOD and elevated mitochondria-derived superoxide, contributes to the reduced Na(v) channel activation and cell excitability in the aortic baroreceptor neurons in CHF rats.
authors.affiliation: Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
authors.forename: Huiyin
authors.initials: H
authors.lastname: Tu
authors.forename: Jinxu
authors.initials: J
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhu
authors.forename: Libin
authors.initials: L
authors.lastname: Zhang
authors.forename: Iraklis I
authors.initials: II
authors.lastname: Pipinos
authors.forename: Yu-Long
authors.initials: YL
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001703:Biophysics; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002908:Chronic Disease; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics; D006333:Heart Failure / Q000473:pathology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009620:Nodose Ganglion / Q000473:pathology*; D018408:Patch-Clamp Techniques; D010617:Phenanthridines / Q000378:metabolism; D011311:Pressoreceptors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D013053:Spectrophotometry; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection
chemical_list: C521281:5-(6'-triphenylphosphoniumhexyl)-5,6-dihydro-6-phenyl-3,8-phenanthridinediammine; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D037102:Lectins; D009097:Multienzyme Complexes; D062556:NAV1.7 Voltage-Gated Sodium Channel; D010617:Phenanthridines; C534504:RTA 203; C503480:Scn9a protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012402:Rotenone; D013779:Tetrodotoxin; D000968:Antimycin A; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase
references.citation: Am J Cardiol. 1988 Jun 1;61(15):1292-9
references.pmid: 3376889
references.citation: Circ Res. 2010 Oct 15;107(8):967-74
references.pmid: 20724705
references.citation: Antioxid Redox Signal. 2007 Apr;9(4):409-35
references.pmid: 17280484
references.citation: Heart Lung Circ. 2009 Feb;18(1):3-10
references.pmid: 19119068
references.citation: Free Radic Biol Med. 2000 Aug;29(3-4):222-30
references.pmid: 11035250
references.citation: Circ Res. 1999 Aug 20;85(4):357-63
references.pmid: 10455064
references.citation: Clin Exp Pharmacol Physiol. 2002 Apr;29(4):305-11
references.pmid: 11985541
references.citation: Anal Biochem. 1976 Feb;70(2):616-20
references.pmid: 817618
references.citation: Am J Cardiol. 1992 Feb 15;69(5):523-31
references.pmid: 1736618
references.citation: Am J Physiol Cell Physiol. 2008 Jan;294(1):C372-9
references.pmid: 18032528
references.citation: J Clin Invest. 2005 Mar;115(3):500-8
references.pmid: 15765131
references.citation: Circulation. 1986 Nov;74(5):929-38
references.pmid: 3021356
references.citation: J Neurosci Res. 2010 Nov 15;88(15):3337-49
references.pmid: 20857502
references.citation: Am J Physiol Renal Physiol. 2006 Jan;290(1):F14-9
references.pmid: 16339961
references.citation: Cardiovasc Res. 2007 Aug 1;75(3):546-54
references.pmid: 17499230
references.citation: Anal Biochem. 1971 Nov;44(1):276-87
references.pmid: 4943714
references.citation: Anal Biochem. 1984 Nov 1;142(2):290-6
references.pmid: 6099057
references.citation: Methods Enzymol. 1996;264:555-66
references.pmid: 8965726
references.citation: Free Radic Biol Med. 2003 Aug 1;35(3):236-56
references.pmid: 12885586
references.citation: J Clin Invest. 1996 Jul 15;98(2):345-51
references.pmid: 8755643
references.citation: Arch Biochem Biophys. 1977 Apr 30;180(2):248-57
references.pmid: 195520
references.citation: Nat Med. 1998 Jun;4(6):698-704
references.pmid: 9623979
references.citation: Biochim Biophys Acta. 2007 Mar;1772(3):373-81
references.pmid: 17289351
references.citation: J Neurophysiol. 1986 Mar;55(3):527-39
references.pmid: 2420945
references.citation: J Neurophysiol. 2006 Dec;96(6):3314-22
references.pmid: 16899637
references.citation: Circ Res. 1991 May;68(5):1294-301
references.pmid: 2018993
references.citation: Clin Chim Acta. 1994 Oct 31;230(2):177-87
references.pmid: 7834868
references.citation: Chem Senses. 2008 Jun;33(5):425-32
references.pmid: 18319263
references.citation: Biochem Med Metab Biol. 1994 Feb;51(1):35-42
references.pmid: 8192914
references.citation: Am J Physiol Renal Physiol. 2006 Dec;291(6):F1148-56
references.pmid: 16822936
references.citation: Eur J Pharmacol. 2011 Jan 10;650(1):328-34
references.pmid: 21036124
references.citation: J Physiol. 1999 Jan 1;514 ( Pt 1):125-38
references.pmid: 9831721
references.citation: J Neurophysiol. 1997 Dec;78(6):3198-209
references.pmid: 9405539
references.citation: J Physiol. 2008 Mar 1;586(5):1321-36
references.pmid: 18187475
references.citation: Am J Physiol Heart Circ Physiol. 2010 May;298(5):H1600-7
references.pmid: 20304815
references.citation: Biochim Biophys Acta. 2006 Jul;1763(7):747-58
references.pmid: 16828895
references.citation: Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H570-8
references.pmid: 18083891
references.citation: J Clin Invest. 1990 May;85(5):1362-71
references.pmid: 2332495
references.citation: Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1828-35
references.pmid: 15371269
references.citation: Am J Physiol Cell Physiol. 2010 Apr;298(4):C857-65
references.pmid: 20089930
references.citation: Biochem J. 2009 Jan 1;417(1):1-13
references.pmid: 19061483
references.citation: Novartis Found Symp. 2001;235:247-63; discussion 263-6
references.pmid: 11280029
references.citation: Circulation. 1991 Jan;83(1):260-7
references.pmid: 1984884
references.citation: Hypertension. 2007 Nov;50(5):904-10
references.pmid: 17846349
references.citation: Circulation. 1990 Jun;81(6):1959-66
references.pmid: 2344687
references.citation: Curr Vasc Pharmacol. 2005 Jul;3(3):221-9
references.pmid: 16026319
references.citation: J Am Coll Cardiol. 1994 Feb;23(2):401-5
references.pmid: 8294694
references.citation: Mamm Genome. 2010 Dec;21(11-12):534-42
references.pmid: 21069343
references.citation: J Am Coll Cardiol. 1986 Apr;7(4):758-65
references.pmid: 3514728
references.citation: Cell. 2005 Feb 25;120(4):483-95
references.pmid: 15734681
references.citation: Am J Physiol. 1991 Apr;260(4 Pt 2):H1160-5
references.pmid: 1849369
references.citation: Hum Gene Ther. 1998 Jun 10;9(9):1381-6
references.pmid: 9650622
references.citation: J Physiol. 2003 Oct 15;552(Pt 2):335-44
references.pmid: 14561818
references.citation: J Biol Chem. 2005 Jun 17;280(24):22715-20
references.pmid: 15851472
references.citation: Circ Res. 1989 Dec;65(6):1526-35
references.pmid: 2582588
references.citation: Circulation. 1989 Jan;79(1):51-8
references.pmid: 2642755
references.citation: J Inherit Metab Dis. 1998 Aug;21(5):598-603
references.pmid: 9728339
references.citation: Trends Pharmacol Sci. 2006 Dec;27(12):639-45
references.pmid: 17056127
references.citation: Clin Biochem. 1993 Oct;26(5):351-7
references.pmid: 8299205
references.citation: Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H227-36
references.pmid: 18487441
references.citation: Am J Cardiol. 1992 Jun 4;69(18):10G-15G; discussion 15G-16G
references.pmid: 1626484