Cardiac sodium channel, its mutations and their spectrum of arrhythmia phenotypes
DOI:
https://doi.org/10.7322/jhgd.122759Palavras-chave:
arrhythmia syndromes, action potential, depolarization, cardiac conduction.Resumo
The mechanisms of cellular excitability and propagation of electrical signals in the cardiac muscle are very important functionally and pathologically. The heart is constituted by three types of muscle: atrial, ventricular, and specialized excitatory and conducting fi bers. From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a signifi cant aspect for the diagnosis and treatment of heart diseases. Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. There are areas in the cardiac muscle with anatomical and functional differentiation that present automatism, thus subjecting the rest of the fi bers to their own rhythm. The rate of these (pacemaker) areas could be altered by modifi cations in ions, temperature and especially, the autonomic system. Excitability is a property of the myocardium to react when stimulated. Another electrical property is conductivity, which is characterized by a conduction and activation process, where the action potential, by the all-or-nothing law, travels throughout the heart. Heart relaxation also stands out as an active process, dependent on the energetic output and on specificion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. In the gene mutation aspects that encode the rapid sodium channel (SCN5A gene), this channel is responsible for several phenotypes, such as Brugada syndrome, idiopathic ventricular fibrillation, dilated cardiomyopathy, early repolarization syndrome, familial atrial fibrillation, variant 3 of long QT syndrome, multifocal ectopic ventricular contractions originating in Purkinje arborizations, progressive cardiac conduction defect (Lenègre disease), sudden infant death syndrome, sick sinus syndrome, sudden unexplained nocturnal death syndrome, among other sodium channel alterations with clinical overlapping. Finally, it seems appropriate to consider the “sodium channel syndrome” (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment.
Downloads
Referências
Herfst LJ, Rook MB, Jongsma HJ. Traffi cking and functional expression of cardiac Na (+) channels. J Mol Cell Cardiol. 2004;36(2):185-90. DOI: http://dx.doi.org/10.1016/j.yjmcc.2003.11.014
Swif F, Sjaastad I, Sejersted OM. Does altered regulation of Na+ cause reduced myocardial contractility in heart failure? Tidsskr Nor Laegeforen. 2003;123(21):3036-40.
Noda M, Ikeda T, Kayano T, Suzuki H, Takeshima H, Kurasaki M, et al. Existence of distinct sodium channelmessenger RNAs in rat brain. Nature. 1986;320(6058):188-92. DOI: http://dx.doi.org/10.1038/320188a0
Makielski JC, Sheets MF, Hanck DA, January CT, Fozzard HA. Sodium current in voltage clamped internally perfused canine cardiac Purkinje cells. Biophys. 1987; 52(1):1-11. DOI: http://dx.doi.org/10.1016/S0006-3495(87)83182-X
Patlak JB, Ortiz M. Slow current through single sodium channels of adult rat heart. J Gen Physiol. 1985;86(1):89-104. DOI: http://dx.doi.org/10.1085/jgp.86.1.89
Lederew WJ. Regulation and function of adenosine triphosphate-sensitive potassium channels in the cardiovascular system. In: Zipes DP, Jalife J. Cardiac Electrophysiology from Cell to Bedside. ed. 2, Philadelphia: WB Saunders; 1995.
Wang Q1, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995;80(5):805-11. DOI: http://dx.doi.org/10.1016/0092-8674(95)90359-3
Hodgkin AL, Huxley AF. A quantitative and is application to conduction and excitation in nerve. J Physiol 1952;117:500-44.
Wu SN. Simulations of the cardiac action potential based on the Hodgkin-Huxley kinetics with the use of Microsoft Excel spreadsheets. Chin J Physiol. 2004;47(1):15-22.
Misuiye T, Noma A. Inactivation of cardiac Na+ channel simply through open states as revealed by singlechannel analysis in guinea pig ventricular myocytes. Jpn J Physiol. 2002;52(2):457-69.
Xiao Y, Tang J, Yang Y, Wang M, Hu W, Xie J, et al. Jingzhaotoxin-III, a novel spider toxin inhibiting activation of voltage-gated sodium channel in rat cardiac myocytes. J Biol Chem. 2004;279(25):26220-6. DOI: http://dx.doi.org/10.1074/jbc.M401387200
Fozzard HA, Hanck DA. Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms. Physiol Rev. 1996;76(3):887-960.
Ragsdale DS, McPhee JC, Scheuer T, Catterall WA. Molecular determinants of state-dependent block of Na+ channels by local anesthetics. Science. 1994;265(5179):1724-8.
Wang SY, Mitchell J, Moczydlowski E, Wang GK. Block of inactivation-defi cient Na+ channels by local anesthetics in stably transfected mammalian cells: evidence for drug binding along the activation pathway. J Gen Physiol. 2004;124(6):691-701. DOI: http://dx.doi.org/10.1085/jgp.200409128
Wang Q, Li Z, Shen J, Keating MT. Genomic organization of the human SCN5A gene encoding the cardiac sodium channel. Genomic. 1996;34(1):9-16. DOI: http://dx.doi.org/10.1006/geno.1996.0236
Malhotra JD, Thyagarajan V, Chen C, Isom LL. Tyrosine-phosphorylated- and nonphosphorylated-sodium channel β-1 subunits are differentially localized in cardiac myocytes. J Biol Chem. 2004;279(39):40748-54. DOI: http://dx.doi.org/10.1074/jbc.M407243200
Malhotra JD, Kazen-Gillespie K, Hortsch M, Isom LL. Sodium channel beta subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact. J Biol Chem. 2000;275(15):11383-8. DOI: http://dx.doi.org/10.1074/jbc.275.15.11383
Malhotra JD, Koopmann MC, Kazen-Gillespie KA, Fettman N, Hortsch M, Isom LL. Structural requirements for interaction of sodium channel beta 1 subunits with ankyrin. J Biol Chem. 2002; 277(29):26681-8. DOI: http://dx.doi.org/10.1074/jbc.M202354200
Ragsdale DS, McPhee JC, Scheuer T, Catterall WA. Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsivant block of voltage-gated Na+ channels. Proc Natl Acad Sci USA. 1996;93(17):9270-5.
Rolf S, Bruns HJ, Wichter T, Kirchhof P, Ribbing M, Wasmer K, et al. The ajmaline challenge in Brugada syndrome: diagnostic impact, safety, and recommended protocol. Eur Heart J. 2003;24(12):1104-12. DOI: http://dx.doi.org/10.1016/S0195-668X(03)00195-7
Scherr D, Brunner G, Kaufmann P, Lercher P, Lueger A, Rotman B, et al. Aborted sudden death in a patient with a structurally normal heart: the Brugada syndrome. Intensive Care Med. 2002;28(6):789-92. DOI: http://dx.doi.org/10.1007/s00134-002-1300-z
Brugada R, Brugada J, Antzelevitch C, Kirsch GE, Potenza D, Towbin JA, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation. 2000;101(5):510-15. DOI: http://dx.doi.org/10.1161/01.CIR.101.5.510
Brugada J, Brugada R, Brugada P. Brugada syndrome Arch Mal Coeur Vaiss. 1999; 92(7):847-50.
Schmidt T, Gerckens U, Ortmeyer D, Bootsveld A, Lampe E, Grube E. Brugada syndrome or ARVD (arrhythmogenic right ventricular dysplasia) or both? Signifi cance and value of right precordial ECG changes. Z Kardiol. 2002;91(5):416-22.
Peters S, Trummel M, Denecke S, Koehler B. Results of ajmaline testing in patients with arrhythmogenic right ventricular dysplasia-cardiomyopathy. Int J Cardiol. 2004; 95(2-3):207-10. DOI: http://dx.doi.org/10.1016/j.ijcard.2003.04.032
McKenna WJ, Thiene G, Nava A, Fontaliran F, Blomstrom-Lundqvist C, Fontaine G, et al. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientifi c Council on Cardiomyopathies of the International Society and Federation of Cardiology. Br Heart J. 1994;71(3):215-8.
Chiale PA, Przybylski J, Laiño RA, Halpern MS, Sánchez RA, Gabrieli A, et al. Electrocardiographic changes evoked by ajmaline in chronic Chagas´disease without manifest myocarditis. Am J Cardiol. 1982;49(1):14-20. DOI: http://dx.doi.org/10.1016/0002-9149(82)90271-5
Bertaglia E, Michieletto M, Spedicato L, Pascotto P. Right bundle branch block, intermittent ST segment elevation and inducible ventricular tachycardia in an asymptomatic patient: an unusual presentation of the Brugada syndrome? G Ital Cardiol. 1998;28(8):893-8.
Brugada J, Brugada P. What to do in patients with no structural heart disease and sudden arrhythmic death? Am J Cardiol. 1996;78(5A):69-75.
Eckardt L, Kirchhof P, Johna R, Breithardt G, Borggrefe M, Haverkamp W. Transient local changes in right ventricular monophasic action potentials due to ajmaline in a patient with Brugada syndrome. J Cardiovasc Electrophysiol. 1999; 10(7):1010-5.
Pinar Bermúdez E, García-Alberola A, Martínez Sánchez J, Sánchez Muñoz JJ, Valdés Chávarri M. Spontaneous sustained monomorphic ventricular tachycardia after administration of ajmaline in a patient with Brugada syndrome. Pacing Clin Electrophysiol. 2000;23(3):407-9. DOI: http://dx.doi.org/10.1111/j.1540-8159.2000.tb06771.x
Wendt DJ, Starmer CF, Grant AO. pH dependence of kinetics and steady-state block of cardiac sodium channel by lidocaine. Am J Physiol. 1993;264(5 Pt 2):H1588-98.
Shiraishi H1, Hyogo M, Ishibashi K, Urao N, Tsukamoto M, Keira N, et al. Rate-dependent QRS prolongation during exercise testing associated with hyperkalemia. J Electrocardiol. 2004;37(3):241-5. DOI: http://dx.doi.org/10.1016/j.jelectrocard.2004.02.006
Khan IA, Nair CK. Brugada and long QT-3 syndromes: two phenotypes of the sodium channel disease. Ann Noninvasive Electrocardiol.2004;9(3):280-9. DOI: http://dx.doi.org/10.1111/j.1542-474X.2004.93533.x
Wang GK, Russell C, Wang SY. Mexiletine block of wild-type and inactivation-defi cient human skeletal muscle hNav1.4 Na+ channels. J Physiol. 2004;554(Pt 3):621-33. DOI: http://dx.doi.org/10.1113/jphysiol.2003.054973
Shimizy W, Aiba T, Antzelevitch C. Specifi c therapy based on the genotype and cellular mechanism in inherited cardiac arrhythmias. Long QT syndrome and Brugada syndrome. Curr Pharm Des. 2005;11(12):1561-72.
Chang CC, Acharfi S, Wu MH, Chiang FT, Wang JK, Sung TC, et al. A novel SCN5A mutation manifests as a malignant form of long QT syndrome with perinatal onset of tachycardia/bradycardia. Cardiovasc Res. 2004;64(2):268-78. DOI: http://dx.doi.org/10.1016/j.cardiores.2004.07.007
Ramos E, O’leary ME. State-dependent trapping of flecainide in the cardiac sodium channel. J Physiol. 2004;560(Pt 1):37-49. DOI: http://dx.doi.org/10.1113/jphysiol.2004.065003
Windle JR, Geletka RC, Moss AJ, Zareba W, Atkins DL. Normalization of ventricular repolarization with fl ecainide in long QT syndrome patients with SCN5A: DeltaKPQ mutation. Ann Noninvasive Electrocardiol. 2001; 6(2):153-8.
Ten Harkel ADJ, Wotsenburg M, Jong PL, Wilde AAM. Wijman LJM. Effi cacy of an implantable cardioverterdefibrillator in a neonate with LQT3 associated arrhythmias. Europace. 2005;7(1):77-84. DOI:http://dx.doi.org/10.1016/j.eupc.2004.09.007
Liu H, Clancy C, Cormier J, Kass R. Mutations in cardiac sodium channels: clinical implications. Am J Pharmacogenomics. 2003;3(3):173-9. DOI: http://dx.doi.org/10.2165/00129785-200303030-00003
Ikeda N, Singh BN, Davis LD, Hauswirth O. Effects of flecainide on the electrophysiologic properties of isolated canine and rabbit myocardial fi bers. J Am Coll Cardiol. 1985;5(2 Pt 1):303-10. DOI: http://dx.doi.org/10.1016/S0735-1097(85)80051-6
Wang ZG, Pelletier LC, Talajic M, Nattel S. Effects of flecainide and quinidine on human atrial action potentials. Role of rate-dependence and comparison with guinea pig, rabbit, and dog tissues. Circulation. 1990;82(1):274-83.
Tian XL, Yong SL, Wan X, Wu L, Chung MK, Tchou PJ, et al. Mechanisms by which SCN5A mutation N1325S causes cardiac arrhythmias and sudden death in vivo. Cardiovasc Res. 2004;61(2):256-67. DOI: http://dx.doi.org/10.1016/j.cardiores.2003.11.007
Priori SG, Napolitano C. Genetic defects of cardiac ion channels. The hidden substrate for torsades de pointes. Cardiovasc Drugs Ther. 2002;16:89. DOI: http://dx.doi.org/10.1023/A:1015793113771
Noebels JL. How a Sodium Channel Mutation Causes Epilepsy. Epilepsy Curr. 2003;3(2):70-1. DOI: http://dx.doi.org/10.1046/j.1535-7597.2003.03214.x
Moric-Janiszewska E, Herbert E, Cholewa K, Filipecki A, Trusz-Gluza M, Wilczok T. Mutational screening of SCN5A linked disorders in Polish patients and their family members. J Appl Genet. 2004;45(3):383-90.
Viswanathan PC, Balser JR. Inherited sodium channelopathies: a continuum of channel dysfunction. Trends Cardiovasc Med. 2004;14(1):28-35. DOI: http://dx.doi.org/10.1016/j.tcm.2003.10.001
Napolitano C, Rivolta I, Priori SG. Cardiac sodium channel diseases. Clin Chem Lab Med. 2003;41(4):439-44. DOI: http://dx.doi.org/10.1515/CCLM.2003.066
Antzelevitch C. Molecular biology and cellular mechanisms of Brugada and long QT syndromes in infants and young children. J Electrocardiol. 2001;34(Suppl):177-81. DOI: http://dx.doi.org/10.1054/jelc.2001.0340320
Baroudi G, Napolitano C, Priori SG, Del Bufalo A, Chahine M. Loss of function associated with novel mutations of the SCN5A gene in patients with Brugada syndrome. Can J Cardiol. 2004;20(4):425-30.
Valdivia CR, Tester DJ, Rok BA, Porter CB, Munger TM, Jahangir A, et al. A traffi cking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs. Cardiovasc Res. 2004;62(1):53-62. DOI: http://dx.doi.org/10.1016/j.cardiores.2004.01.022
Ackerman MJ, Siu BL, Sturner WQ, Tester DJ, Valdivia CR, Makielski JC, et al. Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA. 2001;286(18):2264-9. DOI: http://dx.doi.org/10.1001/jama.286.18.2264
Wedekind H, Smits JP, Schulze-Bahr E, Arnold R, Veldkamp MW, Bajanowski T, et al. De novo mutation in the SCN5A gene associated with early onset of sudden infant death. Circulation. 2001;104(10):1158-64. DOI: http://dx.doi.org/10.1161/hc3501.095361
Vatta M, Dumaine R, Varghese G, Richard TA, Shimizu W, Aihara N, et al. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet. 2002;11(3):337-45. DOI: http://dx.doi.org/10.1093/hmg/11.3.337
Akai J, Makita N, Sakurada H, Shirai N, Ueda K, Kitabatake A, et al. A novel SCN5A mutation associated with idiopathic ventricular fi brillation without typical ECG fi ndings of Brugada syndrome. FEBS Lett. 2000;479(1-2):29-34.
Tan HL, Bink-Boelkens MT, Bezzina CR, Viswanathan PC, Beaufort-Krol GC, van Tintelen PJ, et al. A sodium channel mutation causes isolated cardiac conduction disease. Nature. 2001;409(6823):1043-7. DOI: http://dx.doi.org/10.1038/35059090
Baroudi G, Chahine M. Biophysical phenotypes of SCN5A mutations causing long QT and Brugada syndromes. FEBS Lett. 2000;487(2):224-8. DOI: http://dx.doi.org/10.1016/S0014-5793(00)02360-7
Shirai N, Makita N, Sasaki K, Yokoi H, Sakuma I, Sakurada H, et al. A mutant cardiac sodium channel with multiple biophysical defects associated with overlapping clinical features of Brugada syndrome and cardiac conduction disease. Cardiovasc Res. 2002;53(2):348-54. DOI: http://dx.doi.org/10.1016/S0008-6363(01)00494-1
Weiss R, Barmada MM, Nguyen T, Seibel JS, Cavlovich D, Kornblit CA, et al. Clinical and molecular heterogeneity in the Brugada syndrome: a novel gene locus on chromosome 3. Circulation. 2002;105(6):707-13. DOI: http://dx.doi.org/10.1161/hc0602.103618
Grant AO, Carboni MP, Neplioueva V, Starmer CF, Memmi M, Napolitano C, et al. Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation. J Clin Invest. 2002;11098):1201-9. DOI: http://dx.doi.org/10.1172/JCI15570
Lupoglazoff JM, Denjoy I, Cheav T, Berthet M, Extramiana F, Cauchemez B, et al. Homozygotous mutation of the SCN5A gene responsible for congenital long QT syndrome with 2/1 atrioventricular block. Arch Mal Coeur Vaiss. 2002;95(5):440-6.
Rossenbacker T, Carroll SJ, Liu H, Kuipéri C, de Ravel TJ, Devriendt K, et al. Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death. Heart Rhythm. 2004;1(5):610-15. DOI: http://dx.doi.org/10.1016/j.hrthm.2004.07.001
Smits JPP, Koopmann TT, Wilders R, Veldkamp MW, Opthof T, Bhuiyan ZA,et al. A mutation in the human cardiac sodium channel (E161K) contributes to sick sinus syndrome, conduction disease and Brugada syndrome in two families. J Mol Cell Cardiol. 2005;3896):969-81. DOI:http://dx.doi.org/10.1016/j.yjmcc.2005.02.024
Dworakoska B, Dolowy K. Ion channels-related diseases. Acta Biochim Pol. 2000; 47(3):685-703.
Kapur J. Sodium Channel Mutations in GEFS (+) Produce Persistent Inward Current. Epilepsy Curr. 2002;2(5):149-50. DOI: http://dx.doi.org/10.1046/j.1535-7597.2002.00055.x
Clancy CE, Rudy Y. Na (+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation. 2002;105910):1208-13. DOI: http://dx.doi.org/10.1161/hc1002.105183
Abriel H, Wehrens XH, Benhorin J, Kerem B, Kass RS. Molecular pharmacology of the sodium channel mutation D1790G linked to the long-QT syndrome. Circulation. 2000;102(8):921-5.
Choi JS, Tyrrell L, Waxman SG, Dib-Hajj SD. Functional role of the C-terminus of voltage-gated sodium channel Na(v)1.8. FEBS Lett. 2004; 57291-3):256-60. DOI: http://dx.doi.org/10.1016/j.febslet.2004.07.047
Deschenes I, Baroudi G, Berthet M, Barde I, Chalvidan T, Denjoy I, et al. Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes. Cardiovasc Res. 2000;46(1):55-65. DOI: http://dx.doi.org/10.1016/S0008-6363(00)00006-7
Benett PB, Yazawa K, Makita N, et al. Molecular mechanism for an inherited cardiac arrhythmia. Nature. 1995;376(6542):683-5. DOI: http://dx.doi.org/10.1038/376683a0
Balser JR. The cardiac sodium channel: gating function and molecular pharmacology. J Mol Cell Cardiol. 2001;33(4):599-613. DOI: http://dx.doi.org/10.1006/jmcc.2000.1346
Tan HL, Kupershmidt S, Zhang R, Stepanovic S, Roden DM, Wilde AA, et al. A calcium sensor in the sodium channel modulates cardiac excitability. Nature.2002;415(6870):442-7. DOI: http://dx.doi.org/10.1038/415442a
Bers DM. Macromolecular complexes regulating cardiac ryanodine receptor function. J Mol Cell Cardiol. 2004;37(2):417-29. DOI: http://dx.doi.org/10.1016/j.yjmcc.2004.05.026
Shimizu W, Antzelevitch C, Suyama K, Kurita T, Taguchi A, Aihara N, et al. Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2000;11(12):1320-9. DOI: http://dx.doi.org/10.1046/j.1540-8167.2000.01320.x
Rivolta I, Abriel H, Tateyama M, Liu H, Memmi M, Vardas P, et al. Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes. J Biol Chem. 2001; 276(33):30623-30. DOI: http://dx.doi.org/10.1074/jbc.M104471200
Bezzina C, Veldkamp MW, van Den Berg MP, Postma AV, Rook MB, Viersma JW, et al. A single Na (+) channel mutation causing both long-QT and Brugada syndromes. Circ Res. 1999;85(12):1206-13.
Maia IG, Soares MW, Boghossian SH, Sá R. The Brugada s yndrome. Outcome of one case. Arq Bras Cardiol. 2000;74(5):43745.
Duff HJ, Offord J, West JW, Catterall WA. Class I and IV antiarrhythmic drugs and cytosolic calcium regulate mRNA encoding the sodium channel alpha subunit in rat cardiac muscle. Mol Pharmacol. 1992; 42(4): 570-4.
Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. The Cardiac Arrhythmia Suppression Trial II Investigators. N Engl J Med 1992;327(4):227-33. DOI: http://dx.doi.org/10.1056/NEJM199207233270403
Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, et al. Mortality and morbidity in patients receiving encainide, fl ecinide, or placebo. The Cardiac Arrhthmia Supression Trial. N Engl J Med. 1991;324(12):781-8. DOI: http://dx.doi.org/10.1056/NEJM199103213241201
Leaf A, Kang JX. Dietary n-3 fatty acids in the prevention of lethal cardiac arrhtymias. Curr Opin Lipidol. 1997;8(1):4-6.
Kang JX, Leaf A. Prevention fatal cardiac arrhythmias by polyunsaturated fatty acids. Am J Clin Nutr. 2000;71(1 Suppl): 202S-7.
Makita N, Shirai N, Wang DW, Sasaki K, George AL Jr, Kanno M, et al. Cardiac Na (+) channel dysfunction in Brugada syndrome is aggravated by beta (1)-subunit. Circulation. 2000;101:54-60. DOI: http://dx.doi.org/10.1161/01.CIR.101.1.54
Wang DW, Makita N, Kitabatake A, Balser JR, George AL Jr. Enhanced Na (+) channel intermediate inactivation in Brugada syndrome. Circ Res. 2000;87(8):E37-43. DOI: http://dx.doi.org/10.1161/01.RES.87.8.e37
Postema PG, Mosterd A, Hofman N, Alders M, Wilde AA. Sodium Channelopathies: Do We Really Understand What’s Going On? J Cardiovasc Electrophysiol. 2011;22(5):590-3. DOI: http://dx.doi.org/10.1111/j.1540-8167.2010.01892.x
Liu M, Liu H, Dudley SC Jr. Reactive Oxygen Species Originating From Mitochondria Regulate the Cardiac Sodium Channel. Circ Res. 2010;107(8):967-74. DOI: http://dx.doi.org/10.1161/CIRCRESAHA.110.220673
Branco AT. The evolution of genetics to genomics. J Hum Growth Dev. 26(1): 28-32. Doi: http://dx.doi.org/10.7322/jhgd.113710
Downloads
Publicado
Edição
Seção
Licença
CODE OF CONDUCT FOR JOURNAL PUBLISHERS
Publishers who are Committee on Publication Ethics members and who support COPE membership for journal editors should:
- Follow this code, and encourage the editors they work with to follow the COPE Code of Conduct for Journal Edi- tors (http://publicationethics.org/files/u2/New_Code.pdf)
- Ensure the editors and journals they work with are aware of what their membership of COPE provides and en- tails
- Provide reasonable practical support to editors so that they can follow the COPE Code of Conduct for Journal Editors (http://publicationethics.org/files/u2/New_Code.pdf_)
Publishers should:
- Define the relationship between publisher, editor and other parties in a contract
- Respect privacy (for example, for research participants, for authors, for peer reviewers)
- Protect intellectual property and copyright
- Foster editorial independence
Publishers should work with journal editors to:
- Set journal policies appropriately and aim to meet those policies, particularly with respect to:
– Editorial independence
– Research ethics, including confidentiality, consent, and the special requirements for human and animal research
– Authorship
– Transparency and integrity (for example, conflicts of interest, research funding, reporting standards
– Peer review and the role of the editorial team beyond that of the journal editor
– Appeals and complaints
- Communicate journal policies (for example, to authors, readers, peer reviewers)
- Review journal policies periodically, particularly with respect to new recommendations from the COPE
- Code of Conduct for Editors and the COPE Best Practice Guidelines
- Maintain the integrity of the academic record
- Assist the parties (for example, institutions, grant funders, governing bodies) responsible for the investigation of suspected research and publication misconduct and, where possible, facilitate in the resolution of these cases
- Publish corrections, clarifications, and retractions
- Publish content on a timely basis
