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Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels

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Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels. / O' Brien, Sian; Holmes, Andrew P; Johnson, Daniel M; Kabir, S Nashitha; O' Shea, Christopher; O' Reilly, Molly; Avezzu, Adelisa; Reyat, Jasmeet S; Hall, Amelia W; Apicella, Clara; Ellinor, Patrick T; Niederer, Steven; Tucker, Nathan R; Fabritz, Larissa; Kirchhof, Paulus; Pavlovic, Davor.

In: J MOL CELL CARDIOL, Vol. 166, 05.2022, p. 23-35.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

O' Brien, S, Holmes, AP, Johnson, DM, Kabir, SN, O' Shea, C, O' Reilly, M, Avezzu, A, Reyat, JS, Hall, AW, Apicella, C, Ellinor, PT, Niederer, S, Tucker, NR, Fabritz, L, Kirchhof, P & Pavlovic, D 2022, 'Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels', J MOL CELL CARDIOL, vol. 166, pp. 23-35. https://doi.org/10.1016/j.yjmcc.2022.01.009

APA

O' Brien, S., Holmes, A. P., Johnson, D. M., Kabir, S. N., O' Shea, C., O' Reilly, M., Avezzu, A., Reyat, J. S., Hall, A. W., Apicella, C., Ellinor, P. T., Niederer, S., Tucker, N. R., Fabritz, L., Kirchhof, P., & Pavlovic, D. (2022). Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels. J MOL CELL CARDIOL, 166, 23-35. https://doi.org/10.1016/j.yjmcc.2022.01.009

Vancouver

O' Brien S, Holmes AP, Johnson DM, Kabir SN, O' Shea C, O' Reilly M et al. Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels. J MOL CELL CARDIOL. 2022 May;166:23-35. https://doi.org/10.1016/j.yjmcc.2022.01.009

Bibtex

@article{da6badeec12d40dd9465518448e86eb4,
title = "Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels",
abstract = "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 (INa), leading to reduced maximum upstroke velocity of action potential and slower conduction, in left atria compared to ventricle. Reduced atrial INa is only detected at physiological membrane potentials and is driven by alterations in sodium channel biophysical properties and not by NaV1.5 protein expression. Flecainide displayed greater inhibition of atrial INa, 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.",
keywords = "Action Potentials, Aged, Anti-Arrhythmia Agents/pharmacology, Atrial Fibrillation/metabolism, Flecainide/metabolism, Heart Atria/metabolism, Humans, Sodium/metabolism, Sodium Channel Blockers/pharmacology, Sodium Channels/metabolism",
author = "{O' Brien}, Sian and Holmes, {Andrew P} and Johnson, {Daniel M} and Kabir, {S Nashitha} and {O' Shea}, Christopher and {O' Reilly}, Molly and Adelisa Avezzu and Reyat, {Jasmeet S} and Hall, {Amelia W} and Clara Apicella and Ellinor, {Patrick T} and Steven Niederer and Tucker, {Nathan R} and Larissa Fabritz and Paulus Kirchhof and Davor Pavlovic",
note = "Copyright {\textcopyright} 2022 Elsevier Ltd. All rights reserved.",
year = "2022",
month = may,
doi = "10.1016/j.yjmcc.2022.01.009",
language = "English",
volume = "166",
pages = "23--35",
journal = "J MOL CELL CARDIOL",
issn = "0022-2828",
publisher = "Academic Press Inc.",

}

RIS

TY - JOUR

T1 - Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels

AU - O' Brien, Sian

AU - Holmes, Andrew P

AU - Johnson, Daniel M

AU - Kabir, S Nashitha

AU - O' Shea, Christopher

AU - O' Reilly, Molly

AU - Avezzu, Adelisa

AU - Reyat, Jasmeet S

AU - Hall, Amelia W

AU - Apicella, Clara

AU - Ellinor, Patrick T

AU - Niederer, Steven

AU - Tucker, Nathan R

AU - Fabritz, Larissa

AU - Kirchhof, Paulus

AU - Pavlovic, Davor

N1 - Copyright © 2022 Elsevier Ltd. All rights reserved.

PY - 2022/5

Y1 - 2022/5

N2 - 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 (INa), leading to reduced maximum upstroke velocity of action potential and slower conduction, in left atria compared to ventricle. Reduced atrial INa is only detected at physiological membrane potentials and is driven by alterations in sodium channel biophysical properties and not by NaV1.5 protein expression. Flecainide displayed greater inhibition of atrial INa, 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.

AB - 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 (INa), leading to reduced maximum upstroke velocity of action potential and slower conduction, in left atria compared to ventricle. Reduced atrial INa is only detected at physiological membrane potentials and is driven by alterations in sodium channel biophysical properties and not by NaV1.5 protein expression. Flecainide displayed greater inhibition of atrial INa, 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.

KW - Action Potentials

KW - Aged

KW - Anti-Arrhythmia Agents/pharmacology

KW - Atrial Fibrillation/metabolism

KW - Flecainide/metabolism

KW - Heart Atria/metabolism

KW - Humans

KW - Sodium/metabolism

KW - Sodium Channel Blockers/pharmacology

KW - Sodium Channels/metabolism

U2 - 10.1016/j.yjmcc.2022.01.009

DO - 10.1016/j.yjmcc.2022.01.009

M3 - SCORING: Journal article

C2 - 35114252

VL - 166

SP - 23

EP - 35

JO - J MOL CELL CARDIOL

JF - J MOL CELL CARDIOL

SN - 0022-2828

ER -