AJP - Heart Watch the video to see how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 280: H354-H360, 2001;
0363-6135/01 $5.00
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 Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (22)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wan, X.
Right arrow Articles by Kirsch, G. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wan, X.
Right arrow Articles by Kirsch, G. E.
Vol. 280, Issue 1, H354-H360, January 2001

Accelerated inactivation in a mutant Na+ channel associated with idiopathic ventricular fibrillation

Xiaoping Wan1, Shenghan Chen2, Azita Sadeghpour2, Qing Wang2, and Glenn E. Kirsch1

1 Department of Physiology and Biophysics, Rammelkamp Center for Education and Research, Case Western Reserve University, MetroHealth Campus, Cleveland 44109; and 2 Departments of Molecular Cardiology and of Cardiology, Center for Molecular Genetics, The Cleveland Clinic Foundation, Cleveland, Ohio 44195

Idiopathic ventricular fibrillation (IVF) can cause sudden death in both adults and children. One form of IVF (Brugada syndrome), characterized by S-T segment elevation (STE) in the electrocardiogram, has been linked to mutations of SCN5A, the gene encoding the voltage-gated cardiac Na+ channel. A missense mutation of SCN5A that substitutes glutamine for leucine at codon 567 (L567Q, in the cytoplasmic linker between domains I and II) is identified with sudden infant death and Brugada syndrome in one family. However, neither the functional effect of the L567Q mutation nor the molecular mechanism underlying the pathogenicity of the mutation is known. Patch-clamp analysis of L567Q channels expressed in human embryonic kidney cells revealed a marked acceleration and a negative shift in the voltage dependence of inactivation. Unlike other Brugada mutations, this phenotype was expressed independently of temperature or auxiliary beta 1-subunits. These results support a proposed linkage between Brugada syndrome and some instances of sudden infant death and the hypothesis that reduced Na+ conductance is the primary cause of IVF with STE.

SCN5A; Brugada syndrome; arrhythmia; sudden infant death syndrome


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
A. E. Lacerda, Y. A. Kuryshev, Y. Chen, M. Renganathan, H. Eng, S. J. Danthi, J. W. Kramer, T. Yang, and A. M. Brown
Alfuzosin Delays Cardiac Repolarization by a Novel Mechanism
J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 427 - 433.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Z.-S. Zhang, J. Tranquillo, V. Neplioueva, N. Bursac, and A. O. Grant
Sodium channel kinetic changes that produce Brugada syndrome or progressive cardiac conduction system disease
Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H399 - H407.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
Q Wang, S Chen, Q Chen, X Wan, J Shen, G A Hoeltge, A A Timur, M T Keating, and G E Kirsch
The common SCN5A mutation R1193Q causes LQTS-type electrophysiological alterations of the cardiac sodium channel
J. Med. Genet., May 1, 2004; 41(5): e66 - e66.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
K. H. W. J. ten Tusscher, D. Noble, P. J. Noble, and A. V. Panfilov
A model for human ventricular tissue
Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1573 - H1589.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
B. C. Eloff, E. Gilat, X. Wan, and D. S. Rosenbaum
Pharmacological Modulation of Cardiac Gap Junctions to Enhance Cardiac Conduction: Evidence Supporting a Novel Target for Antiarrhythmic Therapy
Circulation, December 23, 2003; 108(25): 3157 - 3163.
[Abstract] [Full Text] [PDF]

Home page
 EuropaceHome page
E. Moric, E. Herbert, M. Trusz-Gluza, A. Filipecki, U. Mazurek, and T. Wilczok
The implications of genetic mutations in the sodium channel gene (SCN5A)
Europace, January 1, 2003; 5(4): 325 - 334.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. Vatta, R. Dumaine, G. Varghese, T. A. Richard, W. Shimizu, N. Aihara, K. Nademanee, R. Brugada, J. Brugada, G. Veerakul, et al.
Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome
Hum. Mol. Genet., February 1, 2002; 11(3): 337 - 345.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
G. Baroudi, V. Pouliot, I. Denjoy, P. Guicheney, A. Shrier, and M. Chahine
Novel Mechanism for Brugada Syndrome : Defective Surface Localization of an SCN5A Mutant (R1432G)
Circ. Res., June 22, 2001; 88 (12): e78 - e83.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
G. Baroudi, S. Acharfi, C. Larouche, and M. Chahine
Expression and Intracellular Localization of an SCN5A Double Mutant R1232W/T1620M Implicated in Brugada Syndrome
Circ. Res., January 11, 2002; 90 (1): e11 - e16.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online