Kinetics of interaction of disopyramide with the cardiac sodium channel: Fast dissociation from open channels at normal rest potentials

1993 ◽  
Vol 136 (2) ◽  
pp. 199-214 ◽  
Author(s):  
Augustus O. Grant ◽  
David J. Wendt ◽  
Yuri Zilberter ◽  
C. Frank Starmer
Keyword(s):  
Sodium Channel ◽  
Open Channels ◽  
Cardiac Sodium Channel ◽  
Kinetics Of

The sodium channel  -subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart

2001 ◽  
Vol 537 (3) ◽  
pp. 693-700 ◽  
Author(s):  
A. I Fahmi ◽  
M. Patel ◽  
E. B Stevens ◽  
A. L Fowden ◽  
J. E. John ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Kinetics Of

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

Biochemical and biophysical studies of the interaction of class I antiarrhythmic drugs with the cardiac sodium channel

1994 ◽  
Vol 33 (3) ◽  
pp. 277-294 ◽  
Author(s):  
Gerald W. Zamponi ◽  
Henry J. Duff ◽  
Robert J. French ◽  
Robert S. Sheldon
Keyword(s):  
Sodium Channel ◽  
Antiarrhythmic Drugs ◽  
Class I ◽  
Cardiac Sodium Channel ◽  
Biophysical Studies

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 P266Down regulation of the cardiac sodium channel Nav1.5 by the MAGUK protein CASK: role of its functional domains

2018 ◽  
Vol 114 (suppl_1) ◽  
pp. S68-S68
Author(s):  
A Beuriot ◽  
C Eichel ◽  
N Doisne ◽  
F Louault ◽  
A Coulombe ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Functional Domains ◽  
Cardiac Sodium Channel ◽  
Maguk Protein
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