scholarly journals Calcium modulation of cardiac sodium channels

2019 ◽  
Vol 598 (14) ◽  
pp. 2835-2846 ◽  
Author(s):  
Christopher N. Johnson
Keyword(s):  
Sodium Channels ◽  
Calcium Modulation ◽  
Cardiac Sodium Channels

scholarly journals Site-3 toxins and cardiac sodium channels

Toxicon ◽  
2007 ◽  
Vol 49 (2) ◽  
pp. 181-193 ◽  
Author(s):  
Dorothy A. Hanck ◽  
Michael F. Sheets
Keyword(s):  
Sodium Channels ◽  
Cardiac Sodium Channels

Abstract 15420: Resolving a Controversy: Inhibition of Cardiac Ryanodine Receptors is the Principal Mechanism of Antiarrhythmic Action of Flecainide in Catecholaminergic Polymorphic Ventricular Tachycardia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Dmytro O Kryshtal ◽  
Daniel J Blackwell ◽  
Christian L Egly ◽  
Abigail N Smith ◽  
Suzanne M Batiste ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Catecholaminergic Polymorphic Ventricular Tachycardia ◽  
Polymorphic Ventricular Tachycardia ◽  
Antiarrhythmic Action ◽  
Channel Block ◽  
Principal Mechanism ◽  
Cardiac Sodium Channels

Rationale: The class Ic antiarrhythmic drug flecainide prevents ventricular tachyarrhythmia in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), a disease caused by hyperactive cardiac ryanodine receptor (RyR2) calcium (Ca) release. Although flecainide inhibits single RyR2 channels in vitro , reports have claimed that RyR2 inhibition by flecainide is not relevant for its mechanism of antiarrhythmic action and concluded that sodium channel block alone is responsible for flecainide’s efficacy in CPVT. Objective: To determine whether RyR2 block independently contributes to flecainide’s efficacy for suppressing spontaneous sarcoplasmic reticulum (SR) Ca release and for preventing ventricular tachycardia in vivo . Methods and Results: We synthesized N -methyl flecainide analogues (QX-FL and NM-FL) and showed that N -methylation reduces flecainide’s inhibitory potency on RyR2 channels but not on cardiac sodium channels. Antiarrhythmic efficacy was tested utilizing a calsequestrin knockout (Casq2-/-) CPVT mouse model. In membrane-permeabilized Casq2-/- cardiomyocytes — lacking intact sarcolemma and devoid of sodium channel contribution — flecainide, but not its analogues, suppressed RyR2-mediated Ca release at clinically relevant concentrations. In voltage-clamped, intact Casq2-/- cardiomyocytes pretreated with tetrodotoxin (TTX) to inhibit sodium channels and isolate the effect of flecainide on RyR2, flecainide significantly reduced the frequency of spontaneous SR Ca release, while QX-FL and NM-FL did not. In vivo , flecainide effectively suppressed catecholamine-induced ventricular tachyarrhythmias in Casq2-/- mice, whereas NM-FL did not, despite comparable sodium channel block. Conclusions: Flecainide remains an effective inhibitor of RyR2-mediated arrhythmogenic Ca release even when cardiac sodium channels are blocked. In mice with CPVT, sodium channel block alone was not enough to prevent arrhythmias. Hence, RyR2 inhibition by flecainide is critical for its mechanism of antiarrhythmic action.

ChemInform Abstract: Synthesis and Structure-Activity Relationships of 6-Heterocyclic- Substituted Purines as Inactivation Modifiers of Cardiac Sodium Channels.

ChemInform ◽  
2010 ◽  
Vol 26 (45) ◽  
pp. no-no
Author(s):  
K. G. ESTEP ◽  
K. A. JOSEF ◽  
E. R. BACON ◽  
P. M. CARABATEAS ◽  
S. IV RUMNEY ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Cardiac Sodium Channels

scholarly journals Stimulation of Protein Kinase C Inhibits Bursting in Disease-Linked Mutant Human Cardiac Sodium Channels

Circulation ◽  
2003 ◽  
Vol 107 (25) ◽  
pp. 3216-3222 ◽  
Author(s):  
M. Tateyama ◽  
J. Kurokawa ◽  
C. Terrenoire ◽  
I. Rivolta ◽  
R.S. Kass
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Sodium Channels ◽  
Kinase C ◽  
Cardiac Sodium Channels ◽  
Stimulation Of

scholarly journals Characterization of two Bunodosoma granulifera toxins active on cardiac sodium channels

2001 ◽  
Vol 134 (6) ◽  
pp. 1195-1206 ◽  
Author(s):  
Cyril Goudet ◽  
Tania Ferrer ◽  
Loipa Galàn ◽  
Adriana Artiles ◽  
Cesar F V Batista ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Cardiac Sodium Channels

scholarly journals Particulate Matter Induces Cardiac Arrhythmias via Dysregulation of Carotid Body Sensitivity and Cardiac Sodium Channels

2012 ◽  
Vol 46 (4) ◽  
pp. 524-531 ◽  
Author(s):  
Ting Wang ◽  
Gabriel D. Lang ◽  
Liliana Moreno-Vinasco ◽  
Yong Huang ◽  
Sascha N. Goonewardena ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Sodium Channels ◽  
Carotid Body ◽  
Cardiac Arrhythmias ◽  
Cardiac Sodium Channels
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