Scn5a

Summary

Gene Symbol: Scn5a
Description: sodium channel, voltage-gated, type V, alpha
Alias: Nav1.5, Nav1.5c, SkM1, SkM2, mH1, sodium channel protein type 5 subunit alpha, sodium channel protein cardiac muscle subunit alpha, sodium channel protein type V subunit alpha, sodium channel, voltage-gated, type V, alpha polypeptide, voltage-gated sodium channel Nav1.5 variant a, voltage-gated sodium channel Nav1.5 variant b, voltage-gated sodium channel subunit alpha Nav1.5
Species: mouse
Products:     Scn5a

Top Publications

  1. Fredj S, Lindegger N, Sampson K, Carmeliet P, Kass R. Altered Na+ channels promote pause-induced spontaneous diastolic activity in long QT syndrome type 3 myocytes. Circ Res. 2006;99:1225-32 pubmed
  2. Stein M, van Veen T, Remme C, Boulaksil M, Noorman M, van Stuijvenberg L, et al. Combined reduction of intercellular coupling and membrane excitability differentially affects transverse and longitudinal cardiac conduction. Cardiovasc Res. 2009;83:52-60 pubmed publisher
    ..Cx43 and Scn5a(1798insD/+) heterozygous (HZ) mice were crossbred to create a mixed offspring: wild-type (WT, n = 15), Cx43 HZ (n =..
  3. Tian X, Yong S, Wan X, Wu L, Chung M, Tchou P, et al. Mechanisms by which SCN5A mutation N1325S causes cardiac arrhythmias and sudden death in vivo. Cardiovasc Res. 2004;61:256-67 pubmed
    Mutations in the cardiac sodium channel gene SCN5A are responsible for type-3 long QT disease (LQT3)...
  4. Nuyens D, Stengl M, Dugarmaa S, Rossenbacker T, Compernolle V, Rudy Y, et al. Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome. Nat Med. 2001;7:1021-7 pubmed
    Deletion of amino-acid residues 1505-1507 (KPQ) in the cardiac SCN5A Na(+) channel causes autosomal dominant prolongation of the electrocardiographic QT interval (long-QT syndrome type 3 or LQT3)...
  5. Shang L, Pfahnl A, Sanyal S, Jiao Z, Allen J, Banach K, et al. Human heart failure is associated with abnormal C-terminal splicing variants in the cardiac sodium channel. Circ Res. 2007;101:1146-54 pubmed
    Heart failure (HF) is associated with reduced cardiac Na+ channel (SCN5A) current. We hypothesized that abnormal transcriptional regulation of this ion channel during HF could help explain the reduced current...
  6. Remme C, Verkerk A, Nuyens D, van Ginneken A, van Brunschot S, Belterman C, et al. Overlap syndrome of cardiac sodium channel disease in mice carrying the equivalent mutation of human SCN5A-1795insD. Circulation. 2006;114:2584-94 pubmed
    Patients carrying the cardiac sodium channel (SCN5A) mutation 1795insD show sudden nocturnal death and signs of multiple arrhythmia syndromes including bradycardia, conduction delay, QT prolongation, and right precordial ST-elevation...
  7. Martin C, Guzadhur L, Grace A, Lei M, Huang C. Mapping of reentrant spontaneous polymorphic ventricular tachycardia in a Scn5a+/- mouse model. Am J Physiol Heart Circ Physiol. 2011;300:H1853-62 pubmed publisher
    ..the left ventricle and right ventricle (RV) of spontaneously beating Langendorff-perfused wild type (WT) and Scn5a+/- mouse hearts...
  8. van Veen T, Stein M, Royer A, Le Quang K, Charpentier F, Colledge W, et al. Impaired impulse propagation in Scn5a-knockout mice: combined contribution of excitability, connexin expression, and tissue architecture in relation to aging. Circulation. 2005;112:1927-35 pubmed
    The SCN5A sodium channel is a major determinant for cardiac impulse propagation. We used epicardial mapping of the atria, ventricles, and septae to investigate conduction velocity (CV) in Scn5a heterozygous young and old mice...
  9. Thomas G, Killeen M, Grace A, Huang C. Pharmacological separation of early afterdepolarizations from arrhythmogenic substrate in DeltaKPQ Scn5a murine hearts modelling human long QT 3 syndrome. Acta Physiol (Oxf). 2008;192:505-17 pubmed
    ..epicardial monophasic action potentials and arrhythmogenic tendency were compared in isolated wild type (WT) and Scn5a+/Delta hearts perfused with 0.1 and 1 microm propranolol and paced from the right ventricular epicardium...

More Information

Publications81

  1. Tateyama M, Kurokawa J, Terrenoire C, Rivolta I, Kass R. Stimulation of protein kinase C inhibits bursting in disease-linked mutant human cardiac sodium channels. Circulation. 2003;107:3216-22 pubmed
    Mutations in SCN5A, the gene coding for the human cardiac Na+ channel alpha-subunit, are associated with variant 3 of the long-QT syndrome (LQT-3)...
  2. Thomas G, Gurung I, Killeen M, Hakim P, Goddard C, Mahaut Smith M, et al. Effects of L-type Ca2+ channel antagonism on ventricular arrhythmogenesis in murine hearts containing a modification in the Scn5a gene modelling human long QT syndrome 3. J Physiol. 2007;578:85-97 pubmed
    ..antagonism were explored in a gain-of-function murine LQT3 model produced by a DeltaKPQ 1505-1507 deletion in the SCN5A gene...
  3. Wang Q, Shen J, Li Z, Timothy K, Vincent G, Priori S, et al. Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. Hum Mol Genet. 1995;4:1603-7 pubmed
    ..polymorphism (SSCP) and DNA sequence analyses to identify mutations in the cardiac sodium channel gene, SCN5A, in affected members of four LQT families...
  4. Tian X, Cheng Y, Zhang T, Liao M, Yong S, Wang Q. Optical mapping of ventricular arrhythmias in LQTS mice with SCN5A mutation N1325S. Biochem Biophys Res Commun. 2007;352:879-83 pubmed
    Transgenic expression of SCN5A mutation N1325S creates a mouse model for type-3 long QT syndrome (LQT3), TG-NS/LQT3...
  5. Bierhuizen M, Boulaksil M, van Stuijvenberg L, van der Nagel R, Jansen A, Mutsaers N, et al. In calcineurin-induced cardiac hypertrophy expression of Nav1.5, Cx40 and Cx43 is reduced by different mechanisms. J Mol Cell Cardiol. 2008;45:373-84 pubmed publisher
    ..These results provide the molecular rationale for Na(v)1.5, Cx43 and Cx40 downregulation in this model of hypertrophy and failure and the development of the pro-arrhythmic substrate. ..
  6. Stokoe K, Thomas G, Goddard C, Colledge W, Grace A, Huang C. Effects of flecainide and quinidine on arrhythmogenic properties of Scn5a+/Delta murine hearts modelling long QT syndrome 3. J Physiol. 2007;578:69-84 pubmed
    ..of flecainide and quinidine were compared in Langendorff-perfused wild-type (WT), and genetically modified (Scn5a+/Delta) murine hearts modelling LQT3...
  7. Thomas G, Killeen M, Gurung I, Hakim P, Balasubramaniam R, Goddard C, et al. Mechanisms of ventricular arrhythmogenesis in mice following targeted disruption of KCNE1 modelling long QT syndrome 5. J Physiol. 2007;578:99-114 pubmed
    ..These findings suggest arrhythmic effects of reduced outward currents expected in KCNE1-/- hearts and their abolition by antagonism of inward L-type Ca2+ current. ..
  8. Wu J, Zhang Y, Zhang X, Cheng L, Lammers W, Grace A, et al. Altered sinoatrial node function and intra-atrial conduction in murine gain-of-function Scn5a+/?KPQ hearts suggest an overlap syndrome. Am J Physiol Heart Circ Physiol. 2012;302:H1510-23 pubmed publisher
    Mutations in SCN5A, the gene encoding the pore-forming subunit of cardiac Na(+) channels, cause a spectrum of arrhythmic syndromes...
  9. Fabritz L, Kirchhof P, Franz M, Nuyens D, Rossenbacker T, Ottenhof A, et al. Effect of pacing and mexiletine on dispersion of repolarisation and arrhythmias in DeltaKPQ SCN5A (long QT3) mice. Cardiovasc Res. 2003;57:1085-93 pubmed
    ..We therefore studied the effects of pacing and mexiletine in mice with a heterozygous knock-in DeltaKPQ SCN5A(Delta/+) deletion (SCN5A-Tg), a murine LQT3 model.
  10. Arnolds D, Liu F, Fahrenbach J, Kim G, Schillinger K, Smemo S, et al. TBX5 drives Scn5a expression to regulate cardiac conduction system function. J Clin Invest. 2012;122:2509-18 pubmed publisher
    ..studies (GWAS) have identified numerous loci associated with adult human CCS function, including TBX5 and SCN5A. We hypothesized that TBX5, a critical developmental transcription factor, regulates transcriptional networks ..
  11. Leoni A, Gavillet B, Rougier J, Marionneau C, Probst V, Le Scouarnec S, et al. Variable Na(v)1.5 protein expression from the wild-type allele correlates with the penetrance of cardiac conduction disease in the Scn5a(+/-) mouse model. PLoS ONE. 2010;5:e9298 pubmed publisher
    Loss-of-function mutations in SCN5A, the gene encoding Na(v)1.5 Na+ channel, are associated with inherited cardiac conduction defects and Brugada syndrome, which both exhibit variable phenotypic penetrance of conduction defects...
  12. Guzadhur L, Pearcey S, Duehmke R, Jeevaratnam K, Hohmann A, Zhang Y, et al. Atrial arrhythmogenicity in aged Scn5a+/DeltaKPQ mice modeling long QT type 3 syndrome and its relationship to Na+ channel expression and cardiac conduction. Pflugers Arch. 2010;460:593-601 pubmed publisher
    ..The present experiments accordingly assess atrial arrhythmogenicity in aging Scn5a+/KPQ mice modeling long QT3 syndrome in relationship to cardiac Na(+) channel, Nav1.5, expression...
  13. Martin C, Siedlecka U, Kemmerich K, Lawrence J, Cartledge J, Guzadhur L, et al. Reduced Na(+) and higher K(+) channel expression and function contribute to right ventricular origin of arrhythmias in Scn5a+/- mice. Open Biol. 2012;2:120072 pubmed publisher
    ..features predisposing to such arrhythmic tendency and their possible RV localization in a heterozygotic Scn5a+/- murine model. Na(v)1...
  14. Papadatos G, Wallerstein P, Head C, Ratcliff R, Brady P, Benndorf K, et al. Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a. Proc Natl Acad Sci U S A. 2002;99:6210-5 pubmed
    ..In patients, deletions or loss-of-function mutations of the cardiac sodium channel gene, SCN5A, have been associated with a wide range of arrhythmias including bradycardia (heart rate slowing), ..
  15. Royer A, van Veen T, Le Bouter S, Marionneau C, Griol Charhbili V, Leoni A, et al. Mouse model of SCN5A-linked hereditary Lenègre's disease: age-related conduction slowing and myocardial fibrosis. Circulation. 2005;111:1738-46 pubmed
    ..hereditary Lenègre's disease) to a loss-of-function mutation in the gene encoding the main cardiac Na+ channel, SCN5A. In the present study, we investigated heterozygous Scn5a-knockout mice (Scn5a+/- mice) as a model for hereditary ..
  16. Domínguez J, de la Rosa A, Navarro F, Franco D, Aranega A. Tissue distribution and subcellular localization of the cardiac sodium channel during mouse heart development. Cardiovasc Res. 2008;78:45-52 pubmed publisher
    ..aim of this study was to analyse the mRNA expression levels and protein distribution of the cardiac sodium channel Scn5a/Nav1.5 during mouse cardiogenesis...
  17. Lei M, Goddard C, Liu J, Leoni A, Royer A, Fung S, et al. Sinus node dysfunction following targeted disruption of the murine cardiac sodium channel gene Scn5a. J Physiol. 2005;567:387-400 pubmed
    ..examined sino-atrial node (SAN) function in hearts from adult mice with heterozygous targeted disruption of the Scn5a gene to clarify the role of Scn5a-encoded cardiac Na+ channels in normal SAN function and the mechanism(s) by ..
  18. Jeevaratnam K, Zhang Y, Guzadhur L, Duehmke R, Lei M, Grace A, et al. Differences in sino-atrial and atrio-ventricular function with age and sex attributable to the Scn5a+/- mutation in a murine cardiac model. Acta Physiol (Oxf). 2010;200:23-33 pubmed publisher
    To investigate the interacting effects of age and sex on electrocardiographic (ECG) features of Scn5a(+/-) mice modelling Brugada syndrome...
  19. Jeevaratnam K, Poh Tee S, Zhang Y, Rewbury R, Guzadhur L, Duehmke R, et al. Delayed conduction and its implications in murine Scn5a(+/-) hearts: independent and interacting effects of genotype, age, and sex. Pflugers Arch. 2011;461:29-44 pubmed publisher
    We explored for relationships between SCN5A haploinsufficiency, implicated in clinical arrhythmogenicity, and right ventricular (RV) conduction disorders in Langendorff-perfused, male and female, and young (3 months) and old (>12 ..
  20. Stein M, van Veen T, Hauer R, De Bakker J, van Rijen H. A 50% reduction of excitability but not of intercellular coupling affects conduction velocity restitution and activation delay in the mouse heart. PLoS ONE. 2011;6:e20310 pubmed publisher
    ..Clinical studies indicate that SCN5A (excitability) and/or Connexin43 (Cx43, intercellular coupling) expression in heart disease is reduced by ..
  21. Martin C, Grace A, Huang C. Spatial and temporal heterogeneities are localized to the right ventricular outflow tract in a heterozygotic Scn5a mouse model. Am J Physiol Heart Circ Physiol. 2011;300:H605-16 pubmed publisher
    ..monophasic action potentials were recorded from seven epicardial positions in Langendorff-perfused wild-type and Scn5a+/- hearts. VT first appeared in the RVOT, implicating it as an arrhythmogenic focus in Scn5a+/- hearts...
  22. Remme C, Verkerk A, Hoogaars W, Aanhaanen W, Scicluna B, Annink C, et al. The cardiac sodium channel displays differential distribution in the conduction system and transmural heterogeneity in the murine ventricular myocardium. Basic Res Cardiol. 2009;104:511-22 pubmed publisher
    ..Sodium channel Scn5a mRNA and Na(v)1...
  23. Zimmer T, Bollensdorff C, Haufe V, Birch Hirschfeld E, Benndorf K. Mouse heart Na+ channels: primary structure and function of two isoforms and alternatively spliced variants. Am J Physiol Heart Circ Physiol. 2002;282:H1007-17 pubmed
    ..Sequence comparisons indicated that mH1 is highly homologous to rat SCN5A, whereas mH2 is highly homologous to SCN4A, expressed in rat skeletal muscle...
  24. Head C, Balasubramaniam R, Thomas G, Goddard C, Lei M, Colledge W, et al. Paced electrogram fractionation analysis of arrhythmogenic tendency in DeltaKPQ Scn5a mice. J Cardiovasc Electrophysiol. 2005;16:1329-40 pubmed
    Gain-of-function mutations within Scn5a, including the DeltaKPQ 1505-1507 deletion in the inactivation domain compromising myocardial repolarization, are implicated in human long QT 3 syndrome (LQT3), associated with ventricular ..
  25. Liu M, Sanyal S, Gao G, Gurung I, Zhu X, Gaconnet G, et al. Cardiac Na+ current regulation by pyridine nucleotides. Circ Res. 2009;105:737-45 pubmed publisher
    ..The influence of NADH/NAD+ on arrhythmic risk was evaluated in wild-type or SCN5A(+/-) mouse heart. A280V GPD1-L caused a 2.48+/-0.17-fold increase in intracellular NADH level (P<0.001)...
  26. Chakrabarti S, Wu X, Yang Z, Wu L, Yong S, Zhang C, et al. MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada syndrome and sick sinus syndrome. Circ Arrhythm Electrophysiol. 2013;6:392-401 pubmed publisher
    ..Use of MOG1 to enhance Na(v)1.5 trafficking to PM may be a potential personalized therapeutic approach for some patients with Brugada syndrome, dilated cardiomyopathy, and sick sinus syndrome in the future. ..
  27. Luo H, Liang H, Hu X, Tang M. [Expression of Kir2.1, SCN5a and SCN1b channel genes in mouse cardiomyocytes with various electric properties: patch clamp combined with single cell RT-PCR study]. Sheng Li Xue Bao. 2012;64:82-6 pubmed
    ..MDP of ventricular-like cells was the most negative. In parallel, stronger expression of SCN5a, SCN1b and Kir2...
  28. Glynn P, Musa H, Wu X, Unudurthi S, Little S, Qian L, et al. Voltage-Gated Sodium Channel Phosphorylation at Ser571 Regulates Late Current, Arrhythmia, and Cardiac Function In Vivo. Circulation. 2015;132:567-77 pubmed publisher
    ..To determine the in vivo role of Ser571, 2 Scn5a knock-in mouse models were generated expressing either: (1) Nav1...
  29. Musa H, Kline C, Sturm A, Murphy N, Adelman S, Wang C, et al. SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia. Proc Natl Acad Sci U S A. 2015;112:12528-33 pubmed publisher
    ..Here, we provide, to our knowledge, the first evidence that mutations in SCN5A (encodes primary cardiac Nav channel Nav1.5) that alter FHF binding result in human cardiovascular disease...
  30. Shekhar A, Lin X, Liu F, Zhang J, Mo H, Bastarache L, et al. Transcription factor ETV1 is essential for rapid conduction in the heart. J Clin Invest. 2016;126:4444-4459 pubmed publisher
    ..Etv1 was highly expressed in murine PAM and VCS cardiomyocytes, where it regulates expression of Nkx2-5, Gja5, and Scn5a, key cardiac genes required for rapid conduction...
  31. Zakariyah A, Rajgara R, Veinot J, Skerjanc I, Burgon P. Congenital heart defect causing mutation in Nkx2.5 displays in vivo functional deficit. J Mol Cell Cardiol. 2017;105:89-98 pubmed publisher
    ..Collectively, the present study demonstrates that mice with the R141C point mutation in the Nkx2.5 allele phenocopies humans with the NKX2.5 R142C point mutation. ..
  32. Portero V, Casini S, Hoekstra M, Verkerk A, Mengarelli I, Belardinelli L, et al. Anti-arrhythmic potential of the late sodium current inhibitor GS-458967 in murine Scn5a-1798insD+/- and human SCN5A-1795insD+/- iPSC-derived cardiomyocytes. Cardiovasc Res. 2017;113:829-838 pubmed publisher
    ..syndrome model of both gain and loss of sodium channel function, comprising cardiomyocytes derived from both human SCN5A-1795insD+/- induced pluripotent stem cells (hiPSC-CMs) and mice carrying the homologous mutation Scn5a-1798insD+/-...
  33. Liu G, Remme C, Boukens B, Belardinelli L, Rajamani S. Overexpression of SCN5A in mouse heart mimics human syndrome of enhanced atrioventricular nodal conduction. Heart Rhythm. 2015;12:1036-45 pubmed publisher
    ..The purpose of this study was to test the hypothesis that overexpression of SCN5A in the mouse heart may provide an animal model mimicking EAVNC...
  34. Lowe J, Stroud D, Yang T, Hall L, Atack T, Roden D. Increased late sodium current contributes to long QT-related arrhythmia susceptibility in female mice. Cardiovasc Res. 2012;95:300-7 pubmed publisher
    ..Studies were conducted in mice in which the canonical cardiac sodium channel Scn5a locus was disrupted, and expression of human wild-type SCN5A cDNA substituted...
  35. van den Boogaard M, Wong L, Tessadori F, Bakker M, Dreizehnter L, Wakker V, et al. Genetic variation in T-box binding element functionally affects SCN5A/SCN10A enhancer. J Clin Invest. 2012;122:2519-30 pubmed publisher
    ..the enhancers colocalized with ion channel genes repressed by TBX3, including the clustered sodium channel genes Scn5a, essential for cardiac function, and Scn10a...
  36. Zhang Y, Wu J, King J, Huang C, Fraser J. Measurement and interpretation of electrocardiographic QT intervals in murine hearts. Am J Physiol Heart Circ Physiol. 2014;306:H1553-7 pubmed publisher
    ..These findings were confirmed over a range of pacing rates, in low K(+) concentration solutions, and in Scn5a+/?KPQ hearts used to model human long QT syndrome...
  37. Ziane R, Huang H, Moghadaszadeh B, Beggs A, Levesque G, Chahine M. Cell membrane expression of cardiac sodium channel Na(v)1.5 is modulated by alpha-actinin-2 interaction. Biochemistry. 2010;49:166-78 pubmed publisher
    ..Our data suggest that alpha-actinin-2, which is known to regulate the functional expression of the potassium channels, may play a role in anchoring Na(v)1.5 to the membrane by connecting the channel to the actin cytoskeleton network. ..
  38. Fabritz L, Damke D, Emmerich M, Kaufmann S, Theis K, Blana A, et al. Autonomic modulation and antiarrhythmic therapy in a model of long QT syndrome type 3. Cardiovasc Res. 2010;87:60-72 pubmed publisher
    ..sympathetic innervation by autoradiography in heterozygous mice with a knock-in deletion (DeltaKPQ) in the Scn5a gene coding for the cardiac sodium channel and increased late sodium current (LQT3 mice)...
  39. Wan E, Abrams J, Weinberg R, Katchman A, Bayne J, Zakharov S, et al. Aberrant sodium influx causes cardiomyopathy and atrial fibrillation in mice. J Clin Invest. 2016;126:112-22 pubmed publisher
    ..Together, our results indicate that these mice will be important for assessing the cellular mechanisms and potential effectiveness of antiarrhythmic therapies. ..
  40. Liu M, Gu L, Sulkin M, Liu H, Jeong E, Greener I, et al. Mitochondrial dysfunction causing cardiac sodium channel downregulation in cardiomyopathy. J Mol Cell Cardiol. 2013;54:25-34 pubmed publisher
    ..Reducing mitochondrial ROS by application of NAD(+), mitoTEMPO, PKC inhibitors, or PKA activators, restored I(Na). NAD(+) improved conduction velocity in human myopathic hearts. ..
  41. Lemoine M, Duverger J, Naud P, Chartier D, Qi X, Comtois P, et al. Arrhythmogenic left atrial cellular electrophysiology in a murine genetic long QT syndrome model. Cardiovasc Res. 2011;92:67-74 pubmed publisher
    ..Atrial cellular arrhythmia mechanisms have not been defined in congenital LQTS. Therefore, we studied atrial cardiomyocyte electrophysiology in mice with an LQTS3 SCN5A inactivation-impairing mutation (?KPQ heterozygotes).
  42. Jones G, Sang E, Goddard C, Mortishire Smith R, Sweatman B, Haselden J, et al. A functional analysis of mouse models of cardiac disease through metabolic profiling. J Biol Chem. 2005;280:7530-9 pubmed
    ..Thus, this approach is a rapid method of phenotyping mouse models of disease. ..
  43. Shy D, Gillet L, Ogrodnik J, Albesa M, Verkerk A, Wolswinkel R, et al. PDZ domain-binding motif regulates cardiomyocyte compartment-specific NaV1.5 channel expression and function. Circulation. 2014;130:147-60 pubmed publisher
    ..5 at the lateral cardiomyocyte membrane and underline the functional role of lateral NaV1.5 in ventricular conduction. Furthermore, we reveal a clinical relevance of the SIV motif in cardiac disease. ..
  44. Choy L, Yeo J, Tse V, Chan S, Tse G. Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models. Int J Cardiol Heart Vasc. 2016;12:1-10 pubmed
    ..Mouse models can serve as useful systems in which to explore how protein defects contribute to arrhythmias and direct future therapy. ..
  45. Gaborit N, Sakuma R, Wylie J, Kim K, Zhang S, Hui C, et al. Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and postnatal physiology. Development. 2012;139:4007-19 pubmed publisher
    ..Our results have uncovered complex genetic interactions between Irx3 and Irx5 in embryonic cardiac development and postnatal physiology. ..
  46. Lo W, Donermeyer D, Allen P. A voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells. Nat Immunol. 2012;13:880-7 pubmed publisher
    ..Thus, active VGSCs in thymocytes provide a mechanism by which a weak positive selection signal can induce the sustained Ca(2+) signals required for CD4(+) T cell development. ..
  47. Dautova Y, Zhang Y, Sabir I, Grace A, Huang C. Atrial arrhythmogenesis in wild-type and Scn5a+/delta murine hearts modelling LQT3 syndrome. Pflugers Arch. 2009;458:443-57 pubmed publisher
    ..pacing induced atrial arrhythmic episodes in 16 out of 16 (16/16) wild-type (WT) and 7/16 genetically modified Scn5a+/Delta (KPQ) Langendorff-perfused murine hearts modelling LQT3 (P < 0...
  48. Zhang T, Yong S, Tian X, Wang Q. Cardiac-specific overexpression of SCN5A gene leads to shorter P wave duration and PR interval in transgenic mice. Biochem Biophys Res Commun. 2007;355:444-50 pubmed
    The Cardiac sodium channel gene SCN5A plays a critical role in cardiac electrophysiology and its mutations, either gain- or loss-of-functions, are associated with lethal arrhythmias...
  49. Boukens B, Sylva M, de Gier de Vries C, Remme C, Bezzina C, Christoffels V, et al. Reduced sodium channel function unmasks residual embryonic slow conduction in the adult right ventricular outflow tract. Circ Res. 2013;113:137-41 pubmed publisher
    ..Later in the development, Gja1 and Scn5a expression remained lower in the subepicardial myocardium of the RVOT than in RV myocardium...
  50. Burel S, Coyan F, Lorenzini M, Meyer M, Lichti C, BROWN J, et al. C-terminal phosphorylation of NaV1.5 impairs FGF13-dependent regulation of channel inactivation. J Biol Chem. 2017;292:17431-17448 pubmed publisher
    ..5 that impair FGF13-dependent regulation of channel inactivation and may contribute to CaMKIIδc-dependent arrhythmogenic disorders in failing hearts. ..
  51. Schroder E, Lefta M, Zhang X, Bartos D, Feng H, Zhao Y, et al. The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility. Am J Physiol Cell Physiol. 2013;304:C954-65 pubmed publisher
    ..Examination of candidate cardiac ion channel genes showed that Scn5a, which encodes the principle cardiac voltage-gated Na(+) channel (Na(V)1...
  52. Wu L, Nishiyama K, Hollyfield J, Wang Q. Localization of Nav1.5 sodium channel protein in the mouse brain. Neuroreport. 2002;13:2547-51 pubmed
    Na(v)1.5 or SCN5A is a member of the voltage-dependent family of sodium channels. The distribution of Na(v)1.5 protein was investigated in the mouse brain using immunohistochemistry. Immunostaining with a Na(v)1...
  53. Davis R, Casini S, van den Berg C, Hoekstra M, Remme C, Dambrot C, et al. Cardiomyocytes derived from pluripotent stem cells recapitulate electrophysiological characteristics of an overlap syndrome of cardiac sodium channel disease. Circulation. 2012;125:3079-91 pubmed publisher
    ..To address this issue, we generated multiple PSC lines containing a Na(+) channel mutation causing a cardiac Na(+) channel overlap syndrome...
  54. Zhang T, Yong S, Drinko J, Popovic Z, Shryock J, Belardinelli L, et al. LQTS mutation N1325S in cardiac sodium channel gene SCN5A causes cardiomyocyte apoptosis, cardiac fibrosis and contractile dysfunction in mice. Int J Cardiol. 2011;147:239-45 pubmed publisher
    Mutations in the cardiac sodium channel gene SCN5A cause long QT syndrome (LQTS). We previously generated an LQTS mouse model (TG-NS) that overexpresses the LQTS mutation N1325S in SCN5A...
  55. Dautova Y, Zhang Y, Grace A, Huang C. Atrial arrhythmogenic properties in wild-type and Scn5a+/- murine hearts. Exp Physiol. 2010;95:994-1007 pubmed publisher
    Loss- and gain-of-function cardiac Na(+) channel (SCN5A) mutations are associated with the Brugada and long QT type 3 syndromes (LQT3), respectively. Both result in ventricular arrhythmias, but have differing atrial effects...
  56. Gillers B, Chiplunkar A, Aly H, Valenta T, Basler K, Christoffels V, et al. Canonical wnt signaling regulates atrioventricular junction programming and electrophysiological properties. Circ Res. 2015;116:398-406 pubmed publisher
    ..Our data further suggest that ventricular pre-excitation may require both morphological patterning defects, as well as myocardial lineage reprogramming, to allow robust conduction across accessory pathway tissue. ..
  57. Hao M, Lomax A, McKeown S, Reid C, Young H, Bornstein J. Early development of electrical excitability in the mouse enteric nervous system. J Neurosci. 2012;32:10949-60 pubmed publisher
    ..Spontaneous depolarizations resembling excitatory postsynaptic potentials were observed at E12.5. The ENS is one of the earliest parts of the developing nervous system to exhibit mature forms of electrical activity. ..
  58. Liu K, Hipkens S, Yang T, Abraham R, Zhang W, Chopra N, et al. Recombinase-mediated cassette exchange to rapidly and efficiently generate mice with human cardiac sodium channels. Genesis. 2006;44:556-64 pubmed
    b>SCN5A encodes the predominant voltage-gated sodium channel isoform in human heart and nearly 100 variants have now been described and studied in vitro...
  59. Petitprez S, Zmoos A, Ogrodnik J, Balse E, Raad N, El Haou S, et al. SAP97 and dystrophin macromolecular complexes determine two pools of cardiac sodium channels Nav1.5 in cardiomyocytes. Circ Res. 2011;108:294-304 pubmed publisher
    ..These data support a model with at least 2 coexisting pools of Na(v)1.5 channels in cardiomyocytes: one targeted at lateral membranes by the syntrophin-dystrophin complex, and one at intercalated discs by SAP97. ..
  60. Potet F, Beckermann T, Kunic J, George A. Intracellular calcium attenuates late current conducted by mutant human cardiac sodium channels. Circ Arrhythm Electrophysiol. 2015;8:933-41 pubmed publisher
    Mutations of the cardiac voltage-gated sodium channel (SCN5A gene encoding voltage-gated sodium channel [NaV1.5]) cause congenital long-QT syndrome type 3 (LQT3). Most NaV1...
  61. King J, Wickramarachchi C, Kua K, Du Y, Jeevaratnam K, Matthews H, et al. Loss of Nav1.5 expression and function in murine atria containing the RyR2-P2328S gain-of-function mutation. Cardiovasc Res. 2013;99:751-9 pubmed publisher
    ..of CV were investigated in murine RyR2(S/S) hearts and compared with those in wild-type (WT) and slow-conducting Scn5a(+/-) hearts. Picrosirius red staining demonstrated increased fibrosis only in Scn5a(+/-) hearts...
  62. Mao W, You T, Ye B, Li X, Dong H, Hill J, et al. Reactive oxygen species suppress cardiac NaV1.5 expression through Foxo1. PLoS ONE. 2012;7:e32738 pubmed publisher
    Na(V)1.5 is a cardiac voltage-gated Na(+) channel ?subunit and is encoded by the SCN5a gene. The activity of this channel determines cardiac depolarization and electrical conduction...
  63. Huang W, Tang M. Role of sodium channels in the spontaneous excitability of early embryonic cardiomyocytes. Chin J Physiol. 2014;57:188-97 pubmed publisher
    ..And TTX-resistant sodium channels contributed to the initiation of action potentials of early embryonic cardiomyocytes, while TTX-sensitive sodium channels were not involved in initiation of action potentials. ..
  64. Fotia A, Ekberg J, Adams D, Cook D, Poronnik P, Kumar S. Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2. J Biol Chem. 2004;279:28930-5 pubmed
    ..Interestingly, Nedd4 suppressed the activity of Na(v)1.2 and Na(v)1.7 but was a poor inhibitor of Na(v)1.8. Our results provide evidence that Nedd4 and Nedd4-2 are likely to be key regulators of specific neuronal Na(v) channels in vivo. ..
  65. Franken P, Dudley C, Estill S, Barakat M, Thomason R, O Hara B, et al. NPAS2 as a transcriptional regulator of non-rapid eye movement sleep: genotype and sex interactions. Proc Natl Acad Sci U S A. 2006;103:7118-23 pubmed
    ..In contrast, the rebound in NREMS time after SD was compromised only in npas2-/- males. We conclude that NPAS2 plays a role in sleep homeostasis, most likely at the level of the thalamus and cortex, where NPAS2 is abundantly expressed. ..
  66. Tran P, Talbott G, Turbe Doan A, Jacobs D, Schonfeld M, Silva L, et al. Downregulating hedgehog signaling reduces renal cystogenic potential of mouse models. J Am Soc Nephrol. 2014;25:2201-12 pubmed publisher
    ..Thus, enhanced Hedgehog activity may have a general role in renal cystogenesis and thereby present a novel therapeutic target. ..
  67. van den Boogaard M, Smemo S, Burnicka Turek O, Arnolds D, van de Werken H, Klous P, et al. A common genetic variant within SCN10A modulates cardiac SCN5A expression. J Clin Invest. 2014;124:1844-52 pubmed publisher
    ..Here we showed by high-resolution 4C-seq analysis of the Scn10a-Scn5a locus in murine heart tissue that a cardiac enhancer located in Scn10a, encompassing SCN10A functional variant ..
  68. Schroder E, Burgess D, Manning C, Zhao Y, Moss A, Patwardhan A, et al. Light phase-restricted feeding slows basal heart rate to exaggerate the type-3 long QT syndrome phenotype in mice. Am J Physiol Heart Circ Physiol. 2014;307:H1777-85 pubmed publisher
    Long QT syndrome type 3 (LQT3) is caused by mutations in the SCN5A-encoded Nav1.5 channel...
  69. Agullo Pascual E, Lin X, Leo Macias A, Zhang M, Liang F, Li Z, et al. Super-resolution imaging reveals that loss of the C-terminus of connexin43 limits microtubule plus-end capture and NaV1.5 localization at the intercalated disc. Cardiovasc Res. 2014;104:371-81 pubmed publisher
    ..Cx43 is part of a molecular complex that determines capture of the microtubule plus-end at the ID, facilitating cargo delivery. These observations link excitability and electrical coupling through a common molecular mechanism. ..
  70. Wang N, Huo R, Cai B, Lu Y, Ye B, Li X, et al. Activation of Wnt/?-catenin signaling by hydrogen peroxide transcriptionally inhibits NaV1.5 expression. Free Radic Biol Med. 2016;96:34-44 pubmed publisher
    ..suppression requires the interaction of ?-catenin with its nuclear partner, TCF4 (also called TCF7L2) to decrease SCN5a promoter activity...
  71. Schleef M, Werner K, Satzger U, Kaupmann K, Jockusch H. Chromosomal localization and genomic cloning of the mouse alpha-tropomyosin gene Tpm-1. Genomics. 1993;17:519-21 pubmed
    ..Using interspecies backcrosses, we have localized Tpm-1 on mouse chromosome 9, cen-Cyp1a2-Tpm-1-Mod-1-Mylc-Scn5a, near the d-se region...
  72. Albesa M, Ogrodnik J, Rougier J, Abriel H. Regulation of the cardiac sodium channel Nav1.5 by utrophin in dystrophin-deficient mice. Cardiovasc Res. 2011;89:320-8 pubmed publisher
    ..Utrophin plays a central role in the regulation of Na(v)1.5 in mdx mice. These findings provide support for therapeutic strategies aimed at overexpressing utrophin in the hopes of reducing cardiac pathology in DMD patients. ..