A novel microsatellite polymorphism of sodium channel beta1-subunit gene (SCN1B) may underlie abnormal cardiac excitation manifested by coved-type ST-elevation compatible with Brugada syndrome in Japanese

2010 ◽  
Vol 48 (02) ◽  
pp. 109-119 ◽  
Author(s):  
R. Ogawa ◽  
R. Kishi ◽  
A. Takagi ◽  
I. Sakaue ◽  
H. Takahashi ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Brugada Syndrome ◽  
Microsatellite Polymorphism ◽  
Subunit Gene ◽  
St Elevation ◽  
Cardiac Excitation ◽  
Beta1 Subunit

ST ELEVATION AS AN ECG ENDOPHENOTYPE FOR ATRIAL FIBRILLATION PATIENTS HARBORING RARE SODIUM CHANNEL SUBUNIT GENE VARIANTS

Heart Rhythm ◽  
2014 ◽  
Vol 11 (11) ◽  
pp. 2140
Author(s):  
F.O. Ochieng' ◽  
M.J. Kolek ◽  
R.L. Abraham ◽  
G.A. Kucera ◽  
T. Stubblefield ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sodium Channel ◽  
Gene Variants ◽  
Subunit Gene ◽  
St Elevation

scholarly journals Left Axis Deviation in Brugada Syndrome: Vectorcardiographic Evaluation during Ajmaline Provocation Testing Reveals Additional Depolarization Abnormalities

2021 ◽  
Vol 22 (2) ◽  
pp. 484
Author(s):  
Martijn H. van der Ree ◽  
Jeroen Vendrik ◽  
Jan A. Kors ◽  
Ahmad S. Amin ◽  
Arthur A. M. Wilde ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Brugada Syndrome ◽  
Right Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Conduction Delay ◽  
Channel Blockers ◽  
Axis Deviation ◽  
Provocation Testing ◽  
The Right

Patients with Brugada syndrome (BrS) can show a leftward deviation of the frontal QRS-axis upon provocation with sodium channel blockers. The cause of this axis change is unclear. In this study, we aimed to determine (1) the prevalence of this left axis deviation and (2) to evaluate its cause, using the insights that could be derived from vectorcardiograms. Hence, from a large cohort of patients who underwent ajmaline provocation testing (n = 1430), we selected patients in whom a type-1 BrS-ECG was evoked (n = 345). Depolarization and repolarization parameters were analyzed for reconstructed vectorcardiograms and were compared between patients with and without a >30° leftward axis shift. We found (1) that the prevalence of a left axis deviation during provocation testing was 18% and (2) that this left axis deviation was not explained by terminal conduction slowing in the right ventricular outflow tract (4th QRS-loop quartile: +17 ± 14 ms versus +13 ± 15 ms, nonsignificant) but was associated with a more proximal conduction slowing (1st QRS-loop quartile: +12[8;18] ms versus +8[4;12] ms, p < 0.001 and 3rd QRS-loop quartile: +12 ± 10 ms versus +5 ± 7 ms, p < 0.001). There was no important heterogeneity of the action potential morphology (no difference in the ventricular gradient), but a left axis deviation did result in a discordant repolarization (spatial QRS-T angle: 122[59;147]° versus 44[25;91]°, p < 0.001). Thus, although the development of the type-1 BrS-ECG is characterized by a terminal conduction delay in the right ventricle, BrS-patients with a left axis deviation upon sodium channel blocker provocation have an additional proximal conduction slowing, which is associated with a subsequent discordant repolarization. Whether this has implications for risk stratification is still undetermined.

P1597Two novel mutations in SCN5A gene cause enhanced inactivation and lead to Brugada syndrome

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Zaytseva ◽  
A V Karpushev ◽  
A V Karpushev ◽  
Y Fomicheva ◽  
Y Fomicheva ◽  
...  
Keyword(s):  
Steady State ◽  
Sodium Channel ◽  
Brugada Syndrome ◽  
Slow Inactivation ◽  
Fast Inactivation ◽  
Novel Mutations ◽  
Patch Clamp Technique ◽  
Inactivation Curve ◽  
Voltage Gated ◽  
Cardiac Sodium Channel

Abstract Background Mutations in gene SCN5A, encoding cardiac potential-dependent sodium channel Nav1.5, are associated with various arrhythmogenic disorders among which the Brugada syndrome (BrS) and the Long QT syndrome (LQT) are the best characterized. BrS1 is associated with sodium channel dysfunction, which can be reflected by decreased current, impaired activation and enhanced inactivation. We found two novel mutations in our patients with BrS and explored their effect on fast and slow inactivation of cardiac sodium channel. Purpose The aim of this study was to investigate the effect of BrS (Y739D, L1582P) mutations on different inactivation processes in in vitro model. Methods Y739D and L1582P substitutions were introduced in SCN5A cDNA using site-directed mutagenesis. Sodium currents were recorded at room temperature in transfected HEK293-T cells using patch-clamp technique with holding potential −100 mV. In order to access the fast steady-state inactivation curve we used double-pulse protocol with 10 ms prepulses. To analyze voltage-dependence of slow inactivation we used two-pulse protocol with 10s prepulse, 20ms test pulse and 25ms interpulse at −100mV to allow recovery from fast inactivation. Electrophysiological measurements are presented as mean ±SEM. Results Y739D mutation affects highly conserved tyrosine 739 among voltage-gated sodium and calcium channels in the segment IIS2. Mutation L1582P located in the loop IVS4-S5, and leucine in this position is not conserved among voltage-gated channels superfamily. We have shown that Y739D leads to significant changes in both fast and slow inactivation, whereas L1582P enhanced slow inactivation only. Steady-state fast inactivation for Y739D was shifted on 8.9 mV towards more negative potentials compare with that for WT, while L1582P did not enhanced fast inactivation (V1/2 WT: −62.8±1.7 mV; Y739D: −71.7±2.3 mV; L1582P: −58.7±1.4 mV). Slow inactivation was increased for both substitutions (INa (+20mV)/INa (−100mV) WT: 0.45±0.03; Y739D: 0,34±0.09: L1582P: 0.38±0.04). Steady-state fast inactivation Conclusions Both mutations, observed in patients with Brugada syndrome, influence on the slow inactivation process. Enhanced fast inactivation was shown only for Y739D mutant. The more dramatic alterations in sodium channel biophysical characteristics are likely linked with mutated residue conservativity. Acknowledgement/Funding RSF #17-15-01292

Differential effects of cardiac sodium channel mutations on initiation of ventricular arrhythmias in patients with Brugada syndrome

Heart Rhythm ◽  
2009 ◽  
Vol 6 (4) ◽  
pp. 487-492 ◽  
Author(s):  
Hiroshi Morita ◽  
Satoshi Nagase ◽  
Daiji Miura ◽  
Aya Miura ◽  
Shigeki Hiramatsu ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Brugada Syndrome ◽  
Ventricular Arrhythmias ◽  
Differential Effects ◽  
Cardiac Sodium Channel

scholarly journals A cardiac sodium channel mutation identified in Brugada syndrome associated with atrial standstill

2004 ◽  
Vol 255 (1) ◽  
pp. 137-142 ◽  
Author(s):  
N. Takehara ◽  
N. Makita ◽  
J. Kawabe ◽  
N. Sato ◽  
Y. Kawamura ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Brugada Syndrome ◽  
Cardiac Sodium Channel ◽  
Channel Mutation ◽  
Sodium Channel Mutation

scholarly journals B-PO04-024 PREDICTION OF A POSITIVE SODIUM CHANNEL BLOCKER PROVOCATION TEST IN PATIENTS SUSPECTED OF BRUGADA SYNDROME

Heart Rhythm ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. S289
Author(s):  
Martijn Hendrik van der Ree ◽  
Jeroen Vendrik ◽  
Tom E. Verstraelen ◽  
Jan A. Kors ◽  
Ahmad S. Amin ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Brugada Syndrome ◽  
Channel Blocker ◽  
Provocation Test ◽  
Sodium Channel Blocker
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