Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
Circulation. 2001;103:1303-1310

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Malhotra, J. D.
Right arrow Articles by Isom, L. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malhotra, J. D.
Right arrow Articles by Isom, L. L.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Related Collections
Right arrow Cell biology/structural biology
Right arrow Cell signalling/signal transduction
Right arrow Gene expression
Right arrow Ion channels/membrane transport

(Circulation. 2001;103:1303.)
© 2001 American Heart Association, Inc.


Basic Science Reports

Characterization of Sodium Channel {alpha}- and ß-Subunits in Rat and Mouse Cardiac Myocytes

Jyoti Dhar Malhotra, PhD; Chunling Chen, MS; Ilaria Rivolta, PhD; Hugues Abriel, MD, PhD; Ricky Malhotra, PhD; Laura N. Mattei, MS; Frank C. Brosius, MD; Robert S. Kass, PhD; Lori L. Isom, PhD

From the Departments of Pharmacology (J.D.M., C.C., L.N.M., L.L.I.) and Internal Medicine (R.M., F.C.B.), University of Michigan, Ann Arbor, and Department of Pharmacology (I.R., H.A., R.S.K.), Columbia University, College of Physicians and Surgeons, New York, NY.

Correspondence to Lori L. Isom, PhD, Department of Pharmacology, The University of Michigan, 1301 MSRB III, 1150 W Medical Center Dr, Ann Arbor, MI 48109-0632. E-mail lisom{at}umich.edu

Background—Sodium channels isolated from mammalian brain are composed of {alpha}-, ß1-, and ß2-subunits. The composition of sodium channels in cardiac muscle, however, has not been defined, and disagreement exists over which ß-subunits are expressed in the myocytes. Some investigators have demonstrated ß1 expression in heart. Others have not detected any auxiliary subunits. On the basis of Northern blot analysis of total RNA, ß2 expression has been thought to be exclusive to neurons and absent from cardiac muscle.

Methods and Results—The goal of this study was to define the subunit composition of cardiac sodium channels in myocytes. We show that cardiac sodium channels are composed of {alpha}-, ß1-, and ß2-subunits. Nav1.5 and Nav1.1 are expressed in myocytes and are associated with ß1- and ß2-subunits. Immunocytochemical localization of Nav1.1, ß1, and ß2 in adult heart sections showed that these subunits are expressed at the Z lines, as shown previously for Nav1.5. Coexpression of Nav1.5 with ß2 in transfected cells resulted in no detectable changes in sodium current.

Conclusions—Cardiac sodium channels are composed of {alpha}- (Nav1.1 or Nav1.5), ß1-, and ß2-subunits. Although ß1-subunits modulate cardiac sodium channel current, ß2-subunit function in heart may be limited to cell adhesion.


Key Words: cells • signal transduction • genes • ion channels




This article has been cited by other articles:


Home page
Cardiovasc ResHome page
S. Casini, H. L. Tan, I. Demirayak, C. A. Remme, A. S. Amin, B. P. Scicluna, H. Chatyan, J. M. Ruijter, C. R. Bezzina, A. C.G. van Ginneken, et al.
Tubulin polymerization modifies cardiac sodium channel expression and gating
Cardiovasc Res, November 23, 2009; (2009) cvp352v2.
[Abstract] [Full Text] [PDF]


Home page
Circ Arrhythm ElectrophysiolHome page
H. Watanabe, D. Darbar, D. W. Kaiser, K. Jiramongkolchai, S. Chopra, B. S. Donahue, P. J. Kannankeril, and D. M. Roden
Mutations in Sodium Channel {beta}1- and {beta}2-Subunits Associated With Atrial Fibrillation
Circ Arrhythm Electrophysiol, June 1, 2009; 2(3): 268 - 275.
[Abstract] [Full Text] [PDF]


Home page
Circ Cardiovasc GenetHome page
D. Hu, H. Barajas-Martinez, E. Burashnikov, M. Springer, Y. Wu, A. Varro, R. Pfeiffer, T. T. Koopmann, J. M. Cordeiro, A. Guerchicoff, et al.
A Mutation in the {beta}3 Subunit of the Cardiac Sodium Channel Associated With Brugada ECG Phenotype
Circ Cardiovasc Genet, June 1, 2009; 2(3): 270 - 278.
[Abstract] [Full Text] [PDF]


Home page
NeuroscientistHome page
W. J. Brackenbury, M. B.A. Djamgoz, and L. L. Isom
An Emerging Role for Voltage-Gated Na+ Channels in Cellular Migration: Regulation of Central Nervous System Development and Potentiation of Invasive Cancers
Neuroscientist, December 1, 2008; 14(6): 571 - 583.
[Abstract] [PDF]


Home page
J. Biol. Chem.Home page
L. Wu, S. L. Yong, C. Fan, Y. Ni, S. Yoo, T. Zhang, X. Zhang, C. A. Obejero-Paz, H.-J. Rho, T. Ke, et al.
Identification of a New Co-factor, MOG1, Required for the Full Function of Cardiac Sodium Channel Nav1.5
J. Biol. Chem., March 14, 2008; 283(11): 6968 - 6978.
[Abstract] [Full Text] [PDF]


Home page
JCBHome page
J. S. Lowe, O. Palygin, N. Bhasin, T. J. Hund, P. A. Boyden, E. Shibata, M. E. Anderson, and P. J. Mohler
Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway
J. Cell Biol., January 10, 2008; 180(1): 173 - 186.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
B. London, C. Albert, M. E. Anderson, W. R. Giles, D. R. Van Wagoner, E. Balk, G. E. Billman, M. Chung, W. Lands, A. Leaf, et al.
Omega-3 Fatty Acids and Cardiac Arrhythmias: Prior Studies and Recommendations for Future Research: A Report from the National Heart, Lung, and Blood Institute and Office of Dietary Supplements Omega-3 Fatty Acids and Their Role in Cardiac Arrhythmogenesis Workshop
Circulation, September 4, 2007; 116(10): e320 - e335.
[Full Text] [PDF]


Home page
EuropaceHome page
A. O. Verkerk, A. C.G. van Ginneken, T. A.B. van Veen, and H. L. Tan
Effects of heart failure on brain-type Na+ channels in rabbit ventricular myocytes
Europace, August 1, 2007; 9(8): 571 - 577.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
A. Medeiros-Domingo, T. Kaku, D. J. Tester, P. Iturralde-Torres, A. Itty, B. Ye, C. Valdivia, K. Ueda, S. Canizales-Quinteros, M. T. Tusie-Luna, et al.
SCN4B-Encoded Sodium Channel 4 Subunit in Congenital Long-QT Syndrome
Circulation, July 10, 2007; 116(2): 134 - 142.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
D. Johnson and E. S. Bennett
Isoform-specific Effects of the beta2 Subunit on Voltage-gated Sodium Channel Gating
J. Biol. Chem., September 8, 2006; 281(36): 25875 - 25881.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
L. F. Lopez-Santiago, M. Pertin, X. Morisod, C. Chen, S. Hong, J. Wiley, I. Decosterd, and L. L. Isom
Sodium channel beta2 subunits regulate tetrodotoxin-sensitive sodium channels in small dorsal root ganglion neurons and modulate the response to pain.
J. Neurosci., July 26, 2006; 26(30): 7984 - 7994.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
F. Brette and C. H. Orchard
No Apparent Requirement for Neuronal Sodium Channels in Excitation-Contraction Coupling in Rat Ventricular Myocytes
Circ. Res., March 17, 2006; 98(5): 667 - 674.
[Abstract] [Full Text] [PDF]


Home page
JGPHome page
P. J. Stocker and E. S. Bennett
Differential Sialylation Modulates Voltage-gated Na+ Channel Gating throughout the Developing Myocardium
J. Gen. Physiol., February 27, 2006; 127(3): 253 - 265.
[Abstract] [Full Text] [PDF]


Home page
Physiol. GenomicsHome page
P. J. Peeters, J. Aerssens, R. de Hoogt, A. Stanisz, H. W. Gohlmann, K. Hillsley, A. Meulemans, D. Grundy, R. H. Stead, and B. Coulie
Molecular profiling of murine sensory neurons in the nodose and dorsal root ganglia labeled from the peritoneal cavity
Physiol Genomics, February 23, 2006; 24(3): 252 - 263.
[Abstract] [Full Text] [PDF]


Home page
Physiol. Rev.Home page
J. M. Nerbonne and R. S. Kass
Molecular Physiology of Cardiac Repolarization
Physiol Rev, October 1, 2005; 85(4): 1205 - 1253.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
M. Lei, C. Goddard, J. Liu, A.-L. Leoni, A. Royer, S. S.-M. Fung, G. Xiao, A. Ma, H. Zhang, F. Charpentier, et al.
Sinus node dysfunction following targeted disruption of the murine cardiac sodium channel gene Scn5a
J. Physiol., September 1, 2005; 567(2): 387 - 400.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
L.S. Meadows and L.L. Isom
Sodium channels as macromolecular complexes: Implications for inherited arrhythmia syndromes
Cardiovasc Res, August 15, 2005; 67(3): 448 - 458.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
V. Haufe, J. A. Camacho, R. Dumaine, B. Gunther, C. Bollensdorff, G. S. von Banchet, K. Benndorf, and T. Zimmer
Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart
J. Physiol., May 1, 2005; 564(3): 683 - 696.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
J.-S. Rougier, M. X. van Bemmelen, M. C. Bruce, T. Jespersen, B. Gavillet, F. Apotheloz, S. Cordonier, O. Staub, D. Rotin, and H. Abriel
Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins
Am J Physiol Cell Physiol, March 1, 2005; 288(3): C692 - C701.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
V. Haufe, J.M. Cordeiro, T. Zimmer, Y.S. Wu, S. Schiccitano, K. Benndorf, and R. Dumaine
Contribution of neuronal sodium channels to the cardiac fast sodium current INa is greater in dog heart Purkinje fibers than in ventricles
Cardiovasc Res, January 1, 2005; 65(1): 117 - 127.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
D. Johnson, M. L. Montpetit, P. J. Stocker, and E. S. Bennett
The Sialic Acid Component of the {beta}1 Subunit Modulates Voltage-gated Sodium Channel Function
J. Biol. Chem., October 22, 2004; 279(43): 44303 - 44310.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
J. D. Malhotra, V. Thyagarajan, C. Chen, and L. L. Isom
Tyrosine-phosphorylated and Nonphosphorylated Sodium Channel {beta}1 Subunits Are Differentially Localized in Cardiac Myocytes
J. Biol. Chem., September 24, 2004; 279(39): 40748 - 40754.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
M. Lei, S. A. Jones, J. Liu, M. K. Lancaster, S. S.-M. Fung, H. Dobrzynski, P. Camelliti, S. K. G. Maier, D. Noble, and M. R. Boyett
Requirement of neuronal- and cardiac-type sodium channels for murine sinoatrial node pacemaking
J. Physiol., September 15, 2004; 559(3): 835 - 848.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
J. L Alvarez, E. Salinas-Stefanon, G. Orta, T. Ferrer, K. Talavera, L. Galan, and G. Vassort
Occurrence of a tetrodotoxin-sensitive calcium current in rat ventricular myocytes after long-term myocardial infarction
Cardiovasc Res, September 1, 2004; 63(4): 653 - 661.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
M. X. van Bemmelen, J.-S. Rougier, B. Gavillet, F. Apotheloz, D. Daidie, M. Tateyama, I. Rivolta, M. A. Thomas, R. S. Kass, O. Staub, et al.
Cardiac Voltage-Gated Sodium Channel Nav1.5 Is Regulated by Nedd4-2 Mediated Ubiquitination
Circ. Res., August 6, 2004; 95(3): 284 - 291.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
N. C. H. Kerr, F. E. Holmes, and D. Wynick
Novel Isoforms of the Sodium Channels Nav1.8 and Nav1.5 Are Produced by a Conserved Mechanism in Mouse and Rat
J. Biol. Chem., June 4, 2004; 279(23): 24826 - 24833.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
S. K.G. Maier, R. E. Westenbroek, K. A. McCormick, R. Curtis, T. Scheuer, and W. A. Catterall
Distinct Subcellular Localization of Different Sodium Channel {alpha} and {beta} Subunits in Single Ventricular Myocytes From Mouse Heart
Circulation, March 23, 2004; 109(11): 1421 - 1427.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
S. K. G. Maier, R. E. Westenbroek, T. T. Yamanushi, H. Dobrzynski, M. R. Boyett, W. A. Catterall, and T. Scheuer
An unexpected requirement for brain-type sodium channels for control of heart rate in the mouse sinoatrial node
PNAS, March 18, 2003; 100(6): 3507 - 3512.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
C.-j. Liu, S. D. Dib-Hajj, M. Renganathan, T. R. Cummins, and S. G. Waxman
Modulation of the Cardiac Sodium Channel Nav1.5 by Fibroblast Growth Factor Homologous Factor 1B
J. Biol. Chem., January 3, 2003; 278(2): 1029 - 1036.
[Abstract] [Full Text] [PDF]


Home page
Hum Mol GenetHome page
J. A. Kearney, D. A. Buchner, G. de Haan, M. Adamska, S. I. Levin, A. R. Furay, R. L. Albin, J. M. Jones, M. Montal, M. J. Stevens, et al.
Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Nav1.6)
Hum. Mol. Genet., October 15, 2002; 11(22): 2765 - 2775.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
G. Schram, M. Pourrier, P. Melnyk, and S. Nattel
Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function
Circ. Res., May 17, 2002; 90(9): 939 - 950.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
S. K. G. Maier, R. E. Westenbroek, K. A. Schenkman, E. O. Feigl, T. Scheuer, and W. A. Catterall
An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart
PNAS, March 19, 2002; 99(6): 4073 - 4078.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
A. I Fahmi, M. Patel, E. B Stevens, A. L Fowden, J. E. John III, K. Lee, R. Pinnock, K. Morgan, A. P Jackson, and J. I Vandenberg
The sodium channel {beta}-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart
J. Physiol., December 15, 2001; 537(3): 693 - 700.
[Abstract] [Full Text] [PDF]


Home page
NeurologyHome page
J.-F. Desaphy, A. De Luca, P. Tortorella, D. De Vito, A. L. George Jr., and D. Conte Camerino
Gating of myotonic Na channel mutants defines the response to mexiletine and a potent derivative
Neurology, November 27, 2001; 57(10): 1849 - 1857.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
K. Kazarinova-Noyes, J. D. Malhotra, D. P. McEwen, L. N. Mattei, E. O. Berglund, B. Ranscht, S. R. Levinson, M. Schachner, P. Shrager, L. L. Isom, et al.
Contactin Associates with Na+ Channels and Increases Their Functional Expression
J. Neurosci., October 1, 2001; 21(19): 7517 - 7525.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
T. Zimmer, C. Bollensdorff, V. Haufe, E. Birch-Hirschfeld, and K. Benndorf
Mouse heart Na+ channels: primary structure and function of two isoforms and alternatively spliced variants
Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H1007 - H1017.
[Abstract] [Full Text] [PDF]