© 1996 American Heart Association, Inc.
Articles |
Multiple Mechanisms of Na+ Channel– Linked Long-QT Syndrome
From the Rammelkamp Center for Research (R.D., A.M.B., G.E.K.), MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio; the Howard Hughes Medical Institute (Q.W., M.T.K.), University of Utah Health Sciences Center, Salt Lake City; the Department of Molecular Physiology and Biophysics (H.A.H.), Baylor College of Medicine, Houston, Tex; and the Department of Cardiology (P.J.S.), University of Pavia (Italy).
Correspondence to Dr G.E. Kirsch, MetroHealth Medical Center, Rammelkamp Bldg R327, 2500 MetroHealth Dr, Cleveland, OH 44106. E-mail gkirsch@mhnet.mhmc.org.
Abstract Inheritable long-QT syndrome (LQTS) is a disease in
which delayed ventricular repolarization leads to cardiac
arrhythmias and the possibility of sudden death. In the
chromosome 3–linked disease, one mutation of the cardiac
Na+ channel gene results in a deletion of residues 1505 to
1507 (
KPQ), and two mutations result in substitutions (N1325S and
R1644H). We compared all three mutant-channel phenotypes by
heterologous expression in Xenopus oocytes. Each produced a
late phase of inactivation-resistant, mexiletine- and
tetrodotoxin-sensitive whole-cell currents, but the underlying
mechanisms were different at the single-channel level. N1325S and
R1644H showed dispersed reopenings after the initial transient, whereas
KPQ showed both dispersed reopenings and long-lasting bursts.
Thus, two distinct biophysical defects underlie the in vitro
phenotype of persistent current in Na+
channel–linked LQTS, and the additive effects of both are
responsible for making the KPQ phenotype the most severe.
Key Words: human heart • cardiac arrhythmia • Romano-Ward syndrome • site-directed mutagenesis • Na+ channels
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|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 C. Antzelevitch Heterogeneity of cellular repolarization in LQTS: the role of M cells Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K2 - K16. [Abstract] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 J. A. Towbin, Z. Wang, and H. Li Genotype and Severity of Long QT Syndrome Drug Metab. Dispos., April 1, 2001; 29(4): 574 - 579. [Abstract] [Full Text]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 M. W. Veldkamp, P. C. Viswanathan, C. Bezzina, A. Baartscheer, A. A. M. Wilde, and J. R. Balser Two Distinct Congenital Arrhythmias Evoked by a Multidysfunctional Na+ Channel Circ. Res., May 12, 2000; 86 (9): e91 - e97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 K. Ono, T. Kaku, N. Makita, A. Kitabatake, and M. Arita Selective Block of Late Currents in the Delta KPQ Na+ Channel Mutant by Pilsicainide and Lidocaine with Distinct Mechanisms Mol. Pharmacol., February 1, 2000; 57(2): 392 - 400. [Abstract] [Full Text]
|
|
|
|
|
|
T. Nagatomo, C. T. January, and J. C. Makielski Preferential Block of Late Sodium Current in the LQT3 Delta KPQ Mutant by the Class IC Antiarrhythmic Flecainide Mol. Pharmacol., January 1, 2000; 57(1): 101 - 107. [Abstract] [Full Text]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 F. Lehmann-Horn and K. Jurkat-Rott Voltage-Gated Ion Channels and Hereditary Disease Physiol Rev, October 1, 1999; 79(4): 1317 - 1372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
M. P. Blaustein and W. J. Lederer Sodium/Calcium Exchange: Its Physiological Implications Physiol Rev, July 1, 1999; 79(3): 763 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
J. R. Balser Structure and function of the cardiac sodium channels Cardiovasc Res, May 1, 1999; 42(2): 327 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
S. G. Priori, J. Barhanin, R. N. W. Hauer, W. Haverkamp, H. J. Jongsma, A. G. Kleber, W. J. McKenna, D. M. Roden, Y. Rudy, K. Schwartz, et al. Genetic and Molecular Basis of Cardiac Arrhythmias: Impact on Clinical Management Parts I and II Circulation, February 2, 1999; 99(4): 518 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.G. Priori, J. Barhanin, R.N.W. Hauer, W. Haverkamp, H.J. Jongsma, A.G. Kleber, W.J. McKenna, D.M. Roden, Y. Rudy, K. Schwartz, et al. Genetic and molecular basis of cardiac arrhythmias: Impact on clinical management Eur. Heart J., February 1, 1999; 20(3): 174 - 195. [PDF]
|
|
|
|
|
|
J. Brugada, P. Brugada, and R. Brugada The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome Europace, January 1, 1999; 1(3): 156 - 166. [Abstract] [PDF]
|
|
|
|
|
|
F. Sesti and S. A.N. Goldstein Single-Channel Characteristics of Wild-Type IKs Channels and Channels formed with Two MinK Mutants that Cause Long QT Syndrome J. Gen. Physiol., December 1, 1998; 112(6): 651 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nagatomo, Z. Fan, B. Ye, G. S. Tonkovich, C. T. January, J. W. Kyle, and J. C. Makielski Temperature dependence of early and late currents in human cardiac wild-type and long Q-T Delta KPQ Na+ channels Am J Physiol Heart Circ Physiol, December 1, 1998; 275(6): H2016 - H2024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
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|
|
|
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R. Chandra, C. F. Starmer, and A. O. Grant Multiple effects of KPQ deletion mutation on gating of human cardiac Na+ channels expressed in mammalian cells Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1643 - H1654. [Abstract] [Full Text] [PDF]
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H. Li, Q. Chen, A. J. Moss, J. Robinson, V. Goytia, J. C. Perry, G. M. Vincent, S. G. Priori, M. H. Lehmann, S. W. Denfield, et al. New Mutations in the KVLQT1 Potassium Channel That Cause Long-QT Syndrome Circulation, April 7, 1998; 97(13): 1264 - 1269. [Abstract] [Full Text] [PDF]
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S. Nattel Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs Cardiovasc Res, March 1, 1998; 37(3): 567 - 577. [Abstract] [Full Text] [PDF]
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N. G. Kambouris, H. B. Nuss, D. C. Johns, G. F. Tomaselli, E. Marban, and J. R. Balser Phenotypic Characterization of a Novel Long-QT Syndrome Mutation (R1623Q) in the Cardiac Sodium Channel Circulation, February 24, 1998; 97(7): 640 - 644. [Abstract] [Full Text] [PDF]
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R. Dumaine and G. E. Kirsch Mechanism of lidocaine block of late current in long Q-T mutant Na+ channels Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H477 - H487. [Abstract] [Full Text] [PDF]
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M. J. Ackerman and D. E. Clapham Ion Channels -- Basic Science and Clinical Disease N. Engl. J. Med., May 29, 1997; 336(22): 1575 - 1586. [Full Text] [PDF]
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S. Kellenberger, J. W. West, W. A. Catterall, and T. Scheuer Molecular Analysis of Potential Hinge Residues in the Inactivation Gate of Brain Type IIA Na+ Channels J. Gen. Physiol., May 1, 1997; 109(5): 607 - 617. [Abstract] [Full Text] [PDF]
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D. W. Wang, K. Yazawa, A. L. George Jr., and P. B. Bennett Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome PNAS, November 12, 1996; 93(23): 13200 - 13205. [Abstract] [Full Text] [PDF]
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D. M. Roden, R. Lazzara, M. Rosen, P. J. Schwartz, J. Towbin, and G. M. Vincent Multiple Mechanisms in the Long-QT Syndrome: Current Knowledge, Gaps, and Future Directions Circulation, October 15, 1996; 94(8): 1996 - 2012. [Abstract] [Full Text]
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S. G. Priori, C. Napolitano, F. Cantu, A. M. Brown, and P. J. Schwartz Differential Response to Na+ Channel Blockade, ß-Adrenergic Stimulation, and Rapid Pacing in a Cellular Model Mimicking the SCN5A and HERG Defects Present in the Long-QT Syndrome Circ. Res., June 1, 1996; 78(6): 1009 - 1015. [Abstract] [Full Text]
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C.-j. Liu, S. D. Dib-Hajj, and S. G. Waxman Fibroblast Growth Factor Homologous Factor 1B Binds to the C Terminus of the Tetrodotoxin-resistant Sodium Channel rNav1.9a (NaN) J. Biol. Chem., May 25, 2001; 276(22): 18925 - 18933. [Abstract] [Full Text] [PDF]
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H. Abriel, C. Cabo, X. H. T. Wehrens, I. Rivolta, H. K. Motoike, M. Memmi, C. Napolitano, S. G. Priori, and R. S. Kass Novel Arrhythmogenic Mechanism Revealed by a Long-QT Syndrome Mutation in the Cardiac Na+ Channel Circ. Res., April 13, 2001; 88(7): 740 - 745. [Abstract] [Full Text] [PDF]
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C. E. Clancy and Y. Rudy Na+ Channel Mutation That Causes Both Brugada and Long-QT Syndrome Phenotypes: A Simulation Study of Mechanism Circulation, March 12, 2002; 105(10): 1208 - 1213. [Abstract] [Full Text] [PDF]
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