Key result
Flecainide exerts greater sodium channel inhibition and conduction slowing in atrial versus ventricular tissue.
Why the study?
Does flecainide exert greater inhibition of voltage-gated sodium currents and conduction in left atrial cells and tissue compared to ventricular cells and tissue?
Does flecainide exert greater inhibition of voltage-gated sodium currents and conduction in left atrial cells and tissue compared to ventricular cells and tissue?
Intrinsic differences in the biophysical properties of sodium channels between the left atrium and ventricle result in greater atrial sensitivity to flecainide, providing a mechanistic explanation for the relative rarity of ventricular pro-arrhythmia in atrial fibrillation patients treated with sodium channel blockers.
Answers are grounded in this paper and cite their sources.
Supports atrial selectivity of flecainide; leaves open clinical translation from animal models.
Atrial fibrillation (AF) affects over 1% of the population and is a leading cause of stroke and heart failure in the elderly. A feared side effect of sodium channel blocker therapy, ventricular pro-arrhythmia, appears to be relatively rare in patients with AF. The biophysical reasons for this relative safety of sodium blockers are not known. Our data demonstrates intrinsic differences between atrial and ventricular cardiac voltage-gated sodium currents (I Na ), leading to reduced maximum upstroke velocity of action potential and slower conduction, in left atria compared to ventricle. Reduced atrial I Na is only detected at physiological membrane potentials and is driven by alterations in sodium channel biophysical properties and not by Na V 1.5 protein expression. Flecainide displayed greater inhibition of atrial I Na , greater reduction of maximum upstroke velocity of action potential, and slowed conduction in atrial cells and tissue. Our work highlights differences in biophysical properties of sodium channels in left atria and ventricles and their response to flecainide. These differences can explain the relative safety of sodium channel blocker therapy in patients with atrial fibrillation.
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Brien et al. (2022) studied Atrial fibrillation. Flecainide vs. Ventricular cardiac cells and tissue was evaluated on Inhibition of atrial voltage-gated sodium currents (INa), reduction of maximum upstroke velocity of action potential, and conduction slowing. Flecainide displayed greater inhibition of atrial INa, reduced action potential maximum upstroke velocity, and slowed conduction in left atrial versus ventricular cells and tissue.
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