Scn5a

Summary

Gene Symbol: Scn5a
Description: sodium voltage-gated channel alpha subunit 5
Alias: Nav1.5, SCAL, 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 5, alpha subunit, sodium channel, voltage-gated, type V, alpha polypeptide, sodium channel, voltage-gated, type V, alpha subunit, voltage-gated sodium channel Nav1.5c, voltage-gated sodium channel subunit alpha Nav1.5
Species: rat
Products:     Scn5a

Top Publications

  1. 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 ..
  2. Rogart R, Cribbs L, Muglia L, Kephart D, Kaiser M. Molecular cloning of a putative tetrodotoxin-resistant rat heart Na+ channel isoform. Proc Natl Acad Sci U S A. 1989;86:8170-4 pubmed
    ..Thus, this cardiac-specific Na+ channel clone appears to encode a distinct TTX-resistant isoform and is another member of the mammalian Na+ channel multigene family, found in newborn heart and denervated skeletal muscles. ..
  3. Haufe V, Camacho J, Dumaine R, Günther B, Bollensdorff C, von Banchet G, et al. Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. J Physiol. 2005;564:683-96 pubmed
    ..Our data suggest that neuronal and skeletal muscle Na(+) channels contribute to the action potential of cardiomyocytes in the adult mammalian heart. ..
  4. Baroudi G, Acharfi S, Larouche C, Chahine M. Expression and intracellular localization of an SCN5A double mutant R1232W/T1620M implicated in Brugada syndrome. Circ Res. 2002;90:E11-6 pubmed
    Brugada syndrome is an inherited cardiac disorder caused by mutations in the cardiac sodium channel gene, SCN5A, that leads to ventricular fibrillation and sudden death...
  5. 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), ..
  6. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson J, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995;80:805-11 pubmed
    ..5, LQT2 on 7q35-36, and LQT3 on 3p21-24. Here we report genetic linkage between LQT3 and polymorphisms within SCN5A, the cardiac sodium channel gene...
  7. Mohler P, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori S, et al. Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A. 2004;101:17533-8 pubmed
    ..Together with previous work in neurons, these results in cardiomyocytes suggest that ankyrin-G participates in a common pathway for localization of voltage-gated Na(v) channels at sites of function in multiple excitable cell types. ..
  8. Dhar Malhotra J, Chen C, Rivolta I, Abriel H, Malhotra R, Mattei L, et al. Characterization of sodium channel alpha- and beta-subunits in rat and mouse cardiac myocytes. Circulation. 2001;103:1303-10 pubmed
    ..Cardiac sodium channels are composed of alpha- (Nav1.1 or Nav1.5), beta(1)-, and beta(2)-subunits. Although beta(1)-subunits modulate cardiac sodium channel current, beta(2)-subunit function in heart may be limited to cell adhesion. ..
  9. Wang L, Sun L, Zhang Y, Wu H, Li C, Pan Z, et al. Ionic mechanisms underlying action potential prolongation by focal cerebral ischemia in rat ventricular myocytes. Cell Physiol Biochem. 2009;23:305-16 pubmed publisher
    ..Our study represents the first documentation of I(Na), I(to) and I(Ca,L) channelopathy as the major ionic mechanism for cerebral ischemic QT prolongation. ..

More Information

Publications62

  1. Ren C, Li D, Ou S, Wang Y, Lin Y, Zong Z, et al. Cloning and expression of the two new variants of Nav1.5/SCN5A in rat brain. Mol Cell Biochem. 2012;365:139-48 pubmed publisher
    The ?-subunit of tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel (VSGC, Nav1.5/SCN5A) has been found from the rat heart and human neuroblastoma cell line NB-1, but its expression in rat brain has not been identified radically...
  2. Rhett J, Ongstad E, Jourdan J, Gourdie R. Cx43 associates with Na(v)1.5 in the cardiomyocyte perinexus. J Membr Biol. 2012;245:411-22 pubmed publisher
    ..This work provides a detailed characterization of the structure of the perinexus at the GJ edge and indicates that one of its potential functions in the heart may be in facilitating conduction of action potential. ..
  3. Matamoros M, Pérez Hernández M, Guerrero Serna G, Amorós I, Barana A, Núñez M, et al. Nav1.5 N-terminal domain binding to α1-syntrophin increases membrane density of human Kir2.1, Kir2.2 and Nav1.5 channels. Cardiovasc Res. 2016;110:279-90 pubmed publisher
    ..5 channels in Nav1.5-Kir2.x-reciprocal interactions and suggest that the molecular mechanisms controlling atrial and ventricular cellular excitability may be different. ..
  4. Xi Y, Wu G, Yang L, Han K, Du Y, Wang T, et al. Increased late sodium currents are related to transcription of neuronal isoforms in a pressure-overload model. Eur J Heart Fail. 2009;11:749-57 pubmed publisher
    ..5- and 2.7-fold, respectively; SCN3a did not change, whereas SCN5a decreased by approximately 60% in HF. Protein levels paralleled their mRNA expression...
  5. Medeiros Domingo A, Kaku T, Tester D, Iturralde Torres P, Itty A, Ye B, et al. SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome. Circulation. 2007;116:134-42 pubmed
    ..by site-directed mutagenesis and heterologously expressed in HEK293 cells that contained the stably expressed SCN5A-encoded sodium channel alpha-subunit (hNa(V)1.5)...
  6. Vatta M, Ackerman M, Ye B, Makielski J, Ughanze E, Taylor E, et al. Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation. 2006;114:2104-12 pubmed
    ..With the recent observation that the LQT3-associated, SCN5A-encoded cardiac sodium channel localizes in caveolae, which are known membrane microdomains whose major component ..
  7. Wu W, Li G, Wong H, Hui M, Tai E, Lam E, et al. Involvement of Kv1.1 and Nav1.5 in proliferation of gastric epithelial cells. J Cell Physiol. 2006;207:437-44 pubmed
    ..1 or Nav1.5 by RNA interference suppressed RGM-1 cell proliferation. To conclude, our study is the first to delineate the expression of ion channels and their functions as growth modulators in gastric epithelial cells. ..
  8. Olesen M, Jespersen T, Nielsen J, Liang B, Møller D, Hedley P, et al. Mutations in sodium channel ?-subunit SCN3B are associated with early-onset lone atrial fibrillation. Cardiovasc Res. 2011;89:786-93 pubmed publisher
    Atrial fibrillation (AF) is the most frequent arrhythmia. Screening of SCN5A-the gene encoding the ?-subunit of the cardiac sodium channel-has indicated that disturbances of the sodium current may play a central role in the mechanism of ..
  9. Ou S, Kameyama A, Hao L, Horiuchi M, Minobe E, Wang W, et al. Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5A. Eur J Neurosci. 2005;22:793-801 pubmed
    ..Sequence analysis has indicated that hNbR1 is highly homologous with human cardiac Nav1.5/SCN5A with > 99% amino acid identity...
  10. Sekiguchi K, Kanda F, Mitsui S, Kohara N, Chihara K. Fibrillation potentials of denervated rat skeletal muscle are associated with expression of cardiac-type voltage-gated sodium channel isoform Nav1.5. Clin Neurophysiol. 2012;123:1650-5 pubmed publisher
    ..We proposed an altered expression of voltage-gated sodium channel isoforms as a novel mechanism to explain the occurrence of fibrillation potentials following skeletal muscle denervation. ..
  11. Salvage S, King J, Chandrasekharan K, Jafferji D, Guzadhur L, Matthews H, et al. Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murine RyR2-P2328S hearts. Acta Physiol (Oxf). 2015;214:361-75 pubmed publisher
    ..This contrasts with the increased arrhythmic incidence and reduced INa and λ with flecainide in WT. ..
  12. 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...
  13. Liu M, Liu H, Dudley S. Reactive oxygen species originating from mitochondria regulate the cardiac sodium channel. Circ Res. 2010;107:967-74 pubmed publisher
    ..Altering the oxidized to reduced NAD(H) balance can activate mitochondrial ROS production, leading to reduced I(Na). This signaling cascade may help explain the link between altered metabolism, conduction block, and arrhythmic risk. ..
  14. Huang X, Ma A, Yang P, Du Y, Xi Y, Geng T. [Expression and function of voltage-gated Na+ channel isoforms in rat sinoatrial node]. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27:52-5 pubmed
    ..1-/+2.1%, P<0.001). Nav1.1, Nav1.5, Nav1.6 and Nav1.7 are all present in rat sinoatrial node. Although neuronal isoforms are more abundant, Nav1.5 seems to contribute more to activity of the sinoatrial node. ..
  15. Byers M, Westenbroek R. Odontoblasts in developing, mature and ageing rat teeth have multiple phenotypes that variably express all nine voltage-gated sodium channels. Arch Oral Biol. 2011;56:1199-220 pubmed publisher
    ..Our data reveal much greater complexity and niche-specific specialization for odontoblasts than previously demonstrated, with implications for tooth sensitivity. ..
  16. Makita N, Horie M, Nakamura T, Ai T, Sasaki K, Yokoi H, et al. Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation. Circulation. 2002;106:1269-74 pubmed
    ..A novel missense mutation (L1825P) was identified within the C-terminus region of the cardiac Na+ channel (SCN5A)...
  17. Yoo S, Dobrzynski H, Fedorov V, Xu S, Yamanushi T, Jones S, et al. Localization of Na+ channel isoforms at the atrioventricular junction and atrioventricular node in the rat. Circulation. 2006;114:1360-71 pubmed
    ..5 must be the result of impaired conduction in the AVN inputs (inferior nodal extension and transitional zone) or output (bundle branches) rather than the AVN itself (open node and penetrating AV bundle). ..
  18. Malhotra J, Thyagarajan V, Chen C, Isom L. Tyrosine-phosphorylated and nonphosphorylated sodium channel beta1 subunits are differentially localized in cardiac myocytes. J Biol Chem. 2004;279:40748-54 pubmed
    ..5 and pYbeta1 and that these complexes are in close association with both N-cadherin and connexin-43. beta1 phosphorylation appears to regulate its localization to differential subcellular domains. ..
  19. Wang C, Hennessey J, Kirkton R, Wang C, Graham V, Puranam R, et al. Fibroblast growth factor homologous factor 13 regulates Na+ channels and conduction velocity in murine hearts. Circ Res. 2011;109:775-82 pubmed publisher
    ..5 loss-of-function mutations. ..
  20. Valdivia C, Ueda K, Ackerman M, Makielski J. GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A. Am J Physiol Heart Circ Physiol. 2009;297:H1446-52 pubmed publisher
    The SCN5A-encoded cardiac sodium channel underlies excitability in the heart, and dysfunction of sodium current (I(Na)) can cause fatal ventricular arrhythmia in maladies such as long QT syndrome, Brugada syndrome (BrS), and sudden ..
  21. Wang L, Meng X, Yuchi Z, Zhao Z, Xu D, Fedida D, et al. De Novo Mutation in the SCN5A Gene Associated with Brugada Syndrome. Cell Physiol Biochem. 2015;36:2250-62 pubmed publisher
    ..The most common genotype found among BrS patients is caused by mutations in the SCN5A gene, which lead to a loss of function of the cardiac sodium (Na(+)) channel (Nav1.5) by different mechanisms...
  22. van Bemmelen M, Rougier J, Gavillet B, Apothéloz F, Daidié D, Tateyama M, et al. Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 mediated ubiquitination. Circ Res. 2004;95:284-91 pubmed
    ..5. These results demonstrate that Na(v)1.5 can be ubiquitinated in heart tissues and that the ubiquitin-protein ligase Nedd4-2 acts on Na(v)1.5 by decreasing the channel density at the cell surface. ..
  23. Ueda K, Valdivia C, Medeiros Domingo A, Tester D, Vatta M, Farrugia G, et al. Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc Natl Acad Sci U S A. 2008;105:9355-60 pubmed publisher
    ..plasma membrane Ca-ATPase subtype 4b (PMCA4b); SNTA1 also is known to associate with the cardiac sodium channel SCN5A. By using a GST-fusion protein of the C terminus of SCN5A, we showed that WT-SNTA1 interacted with SCN5A, nNOS, ..
  24. Shang L, Sanyal S, Pfahnl A, Jiao Z, Allen J, Liu H, et al. NF-kappaB-dependent transcriptional regulation of the cardiac scn5a sodium channel by angiotensin II. Am J Physiol Cell Physiol. 2008;294:C372-9 pubmed
    ..01). By quantitative real-time RT-PCR, the cardiac Na(+) channel (scn5a) mRNA abundance declined by 47.3% (P < 0.01) in H9c2 myocytes treated for 48 h with 100 nmol/l ANG II...
  25. Biet M, Morin N, Lessard Beaudoin M, Graham R, Duss S, Gagné J, et al. Prolongation of action potential duration and QT interval during epilepsy linked to increased contribution of neuronal sodium channels to cardiac late Na+ current: potential mechanism for sudden death in epilepsy. Circ Arrhythm Electrophysiol. 2015;8:912-20 pubmed publisher
    ..This represents a new paradigm in our understanding of cardiac complications related to epilepsy. ..
  26. Makita N, Seki A, Sumitomo N, Chkourko H, Fukuhara S, Watanabe H, et al. A connexin40 mutation associated with a malignant variant of progressive familial heart block type I. Circ Arrhythm Electrophysiol. 2012;5:163-72 pubmed publisher
    ..PFHBI has been linked to genes such as SCN5A that influence cardiac excitability but not to genes that influence cell-to-cell communication...
  27. Beyder A, Gibbons S, Mazzone A, Strege P, Saravanaperumal S, Sha L, et al. Expression and function of the Scn5a-encoded voltage-gated sodium channel NaV 1.5 in the rat jejunum. Neurogastroenterol Motil. 2016;28:64-73 pubmed publisher
    The SCN5A-encoded voltage-gated sodium channel NaV 1.5 is expressed in human jejunum and colon. Mutations in NaV 1.5 are associated with gastrointestinal motility disorders...
  28. Tester D, Will M, Haglund C, Ackerman M. Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005;2:507-17 pubmed
    ..A cardiac channel gene screen for LQTS-causing mutations in KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6) was performed for 541 consecutive, unrelated patients (358 females, average ..
  29. Chagot B, Potet F, Balser J, Chazin W. Solution NMR structure of the C-terminal EF-hand domain of human cardiac sodium channel NaV1.5. J Biol Chem. 2009;284:6436-45 pubmed publisher
    ..These results suggest a molecular basis for the coupling of the intrinsic (EF-hand domain) and extrinsic (calmodulin) components of the calcium-sensing apparatus of NaV1.5. ..
  30. Liu C, Dib Hajj S, Renganathan M, Cummins T, Waxman S. Modulation of the cardiac sodium channel Nav1.5 by fibroblast growth factor homologous factor 1B. J Biol Chem. 2003;278:1029-36 pubmed
    ..5 channel with FHF1B. This is the first report showing that interaction with a growth factor can modulate properties of a voltage-gated sodium channel. ..
  31. 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. ..
  32. Ashpole N, Herren A, Ginsburg K, Brogan J, Johnson D, Cummins T, et al. Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates cardiac sodium channel NaV1.5 gating by multiple phosphorylation sites. J Biol Chem. 2012;287:19856-69 pubmed publisher
    ..5 at multiple sites (including Thr-594 and Ser-516) appears to be required to evoke loss-of-function changes in gating that could contribute to acquired Brugada syndrome-like effects in heart failure. ..
  33. Allouis M, Le Bouffant F, Wilders R, Peroz D, Schott J, Noireaud J, et al. 14-3-3 is a regulator of the cardiac voltage-gated sodium channel Nav1.5. Circ Res. 2006;98:1538-46 pubmed
    ..Based on these findings, we propose that the 14-3-3 protein is a novel component of the cardiac Na(+) channel acting as a cofactor for the regulation of the cardiac Na(+) current. ..
  34. Li Q, Huang H, Liu G, Lam K, Rutberg J, Green M, et al. Gain-of-function mutation of Nav1.5 in atrial fibrillation enhances cellular excitability and lowers the threshold for action potential firing. Biochem Biophys Res Commun. 2009;380:132-7 pubmed publisher
    Genetic mutations of the cardiac sodium channel (SCN5A) specific only to the phenotype of atrial fibrillation have recently been described...
  35. Morel J, Rannou F, Talarmin H, Giroux Metges M, Pennec J, Dorange G, et al. Sodium channel Na(V)1.5 expression is enhanced in cultured adult rat skeletal muscle fibers. J Membr Biol. 2010;235:109-19 pubmed publisher
    ..Our data evidenced an increase in Na(V)1.5 channels and the involvement of beta subunits in the regulation of sodium current and fiber excitability. ..
  36. Watanabe H, Darbar D, Kaiser D, Jiramongkolchai K, Chopra S, Donahue B, et al. Mutations in sodium channel ?1- and ?2-subunits associated with atrial fibrillation. Circ Arrhythm Electrophysiol. 2009;2:268-75 pubmed publisher
    We and others have reported mutations in the cardiac predominant sodium channel gene SCN5A in patients with atrial fibrillation (AF)...
  37. Rokita A, Anderson M. New therapeutic targets in cardiology: arrhythmias and Ca2+/calmodulin-dependent kinase II (CaMKII). Circulation. 2012;126:2125-39 pubmed publisher
  38. Wang J, Ou S, Wang Y, Kameyama M, Kameyama A, Zong Z. Analysis of four novel variants of Nav1.5/SCN5A cloned from the brain. Neurosci Res. 2009;64:339-47 pubmed publisher
    ..Sequence analysis has indicated that hB1 is highly homologus with human cardiac Nav1.5/SCN5A (hH1) with >98% amino acid identity. Genomic sequence analysis of Nav1...
  39. Hund T, Koval O, Li J, Wright P, Qian L, Snyder J, et al. A ?(IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice. J Clin Invest. 2010;120:3508-19 pubmed publisher
    ..Collectively, our data define an unexpected but indispensable molecular platform that determines membrane excitability in the mouse heart and brain. ..
  40. Valdivia C, Medeiros Domingo A, Ye B, Shen W, Algiers T, Ackerman M, et al. Loss-of-function mutation of the SCN3B-encoded sodium channel {beta}3 subunit associated with a case of idiopathic ventricular fibrillation. Cardiovasc Res. 2010;86:392-400 pubmed publisher
    Loss-of-function mutations in the SCN5A-encoded sodium channel SCN5A or Nav1.5 have been identified in idiopathic ventricular fibrillation (IVF) in the absence of Brugada syndrome phenotype. Nav1...
  41. Sato P, Musa H, Coombs W, Guerrero Serna G, Patino G, Taffet S, et al. Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes. Circ Res. 2009;105:523-6 pubmed publisher
    ..Possible relevance to the pathogenesis of arrhythmogenic right ventricular cardiomyopathy is discussed. ..
  42. Makielski J, Ye B, Valdivia C, Pagel M, Pu J, Tester D, et al. A ubiquitous splice variant and a common polymorphism affect heterologous expression of recombinant human SCN5A heart sodium channels. Circ Res. 2003;93:821-8 pubmed
    Amino acid sequence variations in SCN5A are known to affect function of wild-type channels and also those with coexisting mutations; therefore, it is important to know the exact sequence and function of channels most commonly present in ..
  43. 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...
  44. Chagot B, Chazin W. Solution NMR structure of Apo-calmodulin in complex with the IQ motif of human cardiac sodium channel NaV1.5. J Mol Biol. 2011;406:106-19 pubmed publisher
    ..The structure also provides insight into the biochemical basis for disease-associated mutations that map to the IQ motif in Na(V)1.5. ..
  45. Zhang Y, Wang T, Ma A, Zhou X, Gui J, Wan H, et al. Correlations between clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in the cardiac Na+ channel. Acta Physiol (Oxf). 2008;194:311-23 pubmed publisher
    ..Full clinical evaluation of pedigree members through three generations of a Chinese family combined with SCN5A sequencing from genomic DNA was compared with patch and voltage-clamp results from two independent expression ..
  46. 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...
  47. Zhao C, Wang L, Ma X, Zhu W, Yao L, Cui Y, et al. Cardiac Nav 1.5 is modulated by ubiquitin protein ligase E3 component n-recognin UBR3 and 6. J Cell Mol Med. 2015;19:2143-52 pubmed publisher
    ..Thus, our findings indicate that UBR3/6 regulate cardiomyocyte Nav 1.5 channel protein levels via the ubiquitin-proteasome pathway. It is likely that UBR3/6 have the potential to be a therapeutic target for cardiac arrhythmias. ..
  48. Martínez Mármol R, David M, Sanches R, Roura Ferrer M, Villalonga N, Sorianello E, et al. Voltage-dependent Na+ channel phenotype changes in myoblasts. Consequences for cardiac repair. Cardiovasc Res. 2007;76:430-41 pubmed
    ..5 in skeletal myocytes. Our results indicate that skeletal myotubes adopt a cardiac-like phenotype in cell culture conditions and that the expression of Na(v)1.5 acts as an underlying molecular mechanism. ..
  49. Lopez Santiago L, Meadows L, Ernst S, Chen C, Malhotra J, McEwen D, et al. Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals. J Mol Cell Cardiol. 2007;43:636-47 pubmed
    ..Together, these results suggest that beta1 is critical for normal cardiac excitability and loss of beta1 may be associated with a long QT phenotype. ..
  50. 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...
  51. 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. ..
  52. 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...
  53. Stoetzer C, Voelker M, Doll T, Heineke J, Wegner F, Leffler A. Cardiotoxic Antiemetics Metoclopramide and Domperidone Block Cardiac Voltage-Gated Na+ Channels. Anesth Analg. 2017;124:52-60 pubmed
    ..5. These data suggest that Nav1.5 might be a hitherto unrecognized molecular mechanism of some cardiovascular side effects, for example, malignant arrhythmias of prokinetic and antiemetic agents. ..