scholarly journals Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique

2006 ◽  
Vol 570 (2) ◽  
pp. 237-250 ◽  
Author(s):  
Géza Berecki ◽  
Jan G. Zegers ◽  
Zahurul A. Bhuiyan ◽  
Arie O. Verkerk ◽  
Ronald Wilders ◽  
...  
Keyword(s):  
Action Potential ◽  
Sodium Channel ◽  
Long Qt Syndrome ◽  
Long Qt ◽  
Clamp Technique ◽  
Dynamic Action ◽  
Action Potential Clamp ◽  
Qt Syndrome

Effects of Sodium Channel Block with Mexiletine to Reverse Action Potential Prolongation in In Vitro Models of the Long QT Syndrome

1997 ◽  
Vol 8 (11) ◽  
pp. 1280-1290 ◽  
Author(s):  
SERGE SICOURI ◽  
DANIEL ANTZELEVITCH ◽  
CORY HEILMANN ◽  
CHARLES ANTZELEVITCH
Keyword(s):  
Action Potential ◽  
Sodium Channel ◽  
Long Qt Syndrome ◽  
In Vitro Models ◽  
Channel Block ◽  
Long Qt ◽  
Action Potential Prolongation ◽  
Qt Syndrome

Abstract 5316: hERG 1b as a Potential Target for Inherited and Acquired Long QT Syndrome

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Gail A Robertson ◽  
Harinath Sale ◽  
David Tester ◽  
Thomas J O’Hara ◽  
Pallavi Phartiyal ◽  
...  
Keyword(s):  
Action Potential ◽  
Long Qt Syndrome ◽  
Time Course ◽  
Drug Sensitivity ◽  
Long Qt ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
Acquired Long Qt Syndrome ◽  
293 Cells ◽  
Qt Syndrome

Cardiac I Kr is a critical repolarizing current in the heart and a target for inherited and acquired long QT syndrome. Biochemical studies show that native I Kr channels are heteromers composed of both hERG 1a and 1b subunits, yet our current understanding of I Kr functional properties derives primarily from studies of homo-oligomers of the original hERG 1a isolate. The hERG 1a and 1b subunits are identical except at the amino (NH2) terminus, which in hERG 1b is much shorter and has a unique primary sequence. We compared the biophysical properties of currents produced by hERG 1a and 1a/1b channels expressed in HEK-293 cells at near-physiological temperatures. We found that heteromeric hERG 1a/1b currents are much larger than hERG 1a currents and conduct 80% more charge during an action potential. This surprising difference corresponds to a two-fold increase in the apparent rates of activation and recovery from inactivation, which reduces rectification and facilitates current rebound during repolarization. Kinetic modeling shows these gating differences account quantitatively for the differences in current amplitude between the two channel types. Depending on the action potential model used, loss of 1b predicts an increase in action potential duration of 27 ms (7%) or 41 ms (17%), respectively. Drug sensitivity was also different. Compared to homomeric 1a channels, heteromeric 1a/1b channels were inhibited by E-4031 with a slower time course and a corresponding four-fold positive shift in the IC 50 . Differences in current kinetics and drug sensitivity were modeled by “NH2 mode” gating with conformational states bound by the amino terminus in hERG 1a homomers but not 1a/1b heteromers. The importance of hERG 1b in vivo is supported by the identification of a 1b-specific A8V missense mutation in 1/269 unrelated genotype-negative LQTS patients and absent in 400 control alleles. Mutant 1bA8V expressed alone or with hERG 1a in HEK-293 cells nearly eliminated 1b protein. Thus, mutations specifically disrupting hERG 1b function are expected to reduce cardiac I Kr , prolong QT interval and enhance drug sensitivity, thus representing a potential mechanism underlying inherited or acquired LQTS.

scholarly journals Substitution of a conserved alanine in the domain IIIS4–S5 linker of the cardiac sodium channel causes long QT syndrome

2005 ◽  
Vol 67 (3) ◽  
pp. 459-466 ◽  
Author(s):  
J SMITS ◽  
M VELDKAMP ◽  
C BEZZINA ◽  
Z BHUIYAN ◽  
H WEDEKIND ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Long Qt Syndrome ◽  
Long Qt ◽  
Cardiac Sodium Channel ◽  
Qt Syndrome

Bupivacaine Destabilizes Action Potential Duration in Cellular and Computational Models of Long QT Syndrome 1

2011 ◽  
Vol 113 (6) ◽  
pp. 1365-1373 ◽  
Author(s):  
Alexander P. Schwoerer ◽  
Roman Zenouzi ◽  
Heimo Ehmke ◽  
Patrick Friederich
Keyword(s):  
Action Potential ◽  
Long Qt Syndrome ◽  
Action Potential Duration ◽  
Computational Models ◽  
Long Qt ◽  
Qt Syndrome

A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation

Heart Rhythm ◽  
2008 ◽  
Vol 5 (10) ◽  
pp. 1434-1440 ◽  
Author(s):  
Begoña Benito ◽  
Ramon Brugada ◽  
Rosa Maria Perich ◽  
Eric Lizotte ◽  
Juan Cinca ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sodium Channel ◽  
Long Qt Syndrome ◽  
Long Qt ◽  
Familial Atrial Fibrillation ◽  
Qt Syndrome

Cardiac Sodium Channel Nav1.5 and Drug-Induced Long QT Syndrome

2014 ◽  
Vol 6 (4) ◽  
pp. 777-783
Author(s):  
Hugues Abriel
Keyword(s):  
Sodium Channel ◽  
Long Qt Syndrome ◽  
Long Qt ◽  
Drug Induced ◽  
Cardiac Sodium Channel ◽  
Qt Syndrome

scholarly journals A Heterozygous Deletion Mutation in the Cardiac Sodium Channel Gene SCN5A with Loss- and Gain-of-Function Characteristics Manifests as Isolated Conduction Disease, without Signs of Brugada or Long QT Syndrome

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e67963 ◽  
Author(s):  
Sven Zumhagen ◽  
Marieke W. Veldkamp ◽  
Birgit Stallmeyer ◽  
Antonius Baartscheer ◽  
Lars Eckardt ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Long Qt Syndrome ◽  
Deletion Mutation ◽  
Heterozygous Deletion ◽  
Long Qt ◽  
Gain Of Function ◽  
Channel Gene ◽  
Sodium Channel Gene ◽  
Cardiac Sodium Channel ◽  
Qt Syndrome

scholarly journals Malignant Perinatal Variant of Long-QT Syndrome Caused by a Profoundly Dysfunctional Cardiac Sodium Channel

2008 ◽  
Vol 1 (5) ◽  
pp. 370-378 ◽  
Author(s):  
Dao W. Wang ◽  
Lia Crotti ◽  
Wataru Shimizu ◽  
Matteo Pedrazzini ◽  
Francesco Cantu ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Long Qt Syndrome ◽  
Long Qt ◽  
Cardiac Sodium Channel ◽  
Qt Syndrome
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