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Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation

Aims: Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous evidence in animal models suggests that the gap junction (GJ) adjacent nanodomain – perinexus – is a site capable of independent intercellular communication via ephaptic transmission. Perinexal expansion is associated w...

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Autores principales: Raisch, Tristan B., Yanoff, Matthew S., Larsen, Timothy R., Farooqui, Mohammed A., King, D. Ryan, Veeraraghavan, Rengasayee, Gourdie, Robert G., Baker, Joseph W., Arnold, William S., AlMahameed, Soufian T., Poelzing, Steven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945828/
https://www.ncbi.nlm.nih.gov/pubmed/29780324
http://dx.doi.org/10.3389/fphys.2018.00398
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author Raisch, Tristan B.
Yanoff, Matthew S.
Larsen, Timothy R.
Farooqui, Mohammed A.
King, D. Ryan
Veeraraghavan, Rengasayee
Gourdie, Robert G.
Baker, Joseph W.
Arnold, William S.
AlMahameed, Soufian T.
Poelzing, Steven
author_facet Raisch, Tristan B.
Yanoff, Matthew S.
Larsen, Timothy R.
Farooqui, Mohammed A.
King, D. Ryan
Veeraraghavan, Rengasayee
Gourdie, Robert G.
Baker, Joseph W.
Arnold, William S.
AlMahameed, Soufian T.
Poelzing, Steven
author_sort Raisch, Tristan B.
collection PubMed
description Aims: Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous evidence in animal models suggests that the gap junction (GJ) adjacent nanodomain – perinexus – is a site capable of independent intercellular communication via ephaptic transmission. Perinexal expansion is associated with slowed conduction and increased ventricular arrhythmias in animal models, but has not been studied in human tissue. The purpose of this study was to characterize the perinexus in humans and determine if perinexal expansion associates with AF. Methods: Atrial appendages from 39 patients (pts) undergoing cardiac surgery were fixed for immunofluorescence and transmission electron microscopy (TEM). Intercalated disk distribution of the cardiac sodium channel Nav1.5, its β1 subunit, and connexin43 (C×43) was determined by confocal immunofluorescence. Perinexal width (Wp) from TEM was manually segmented by two blinded observers using ImageJ software. Results: Nav1.5, β1, and C×43 are co-adjacent within intercalated disks of human atria, consistent with perinexal protein distributions in ventricular tissue of other species. TEM revealed that the GJ adjacent intermembrane separation in an individual perinexus does not change at distances greater than 30 nm from the GJ edge. Importantly, Wp is significantly wider in patients with a history of AF than in patients with no history of AF by approximately 3 nm, and Wp correlates with age (R = 0.7, p < 0.05). Conclusion: Human atrial myocytes have voltage-gated sodium channels in a dynamic intercellular cleft adjacent to GJs that is consistent with previous descriptions of the perinexus. Further, perinexal width is greater in patients with AF undergoing cardiac surgery than in those without.
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spelling pubmed-59458282018-05-18 Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation Raisch, Tristan B. Yanoff, Matthew S. Larsen, Timothy R. Farooqui, Mohammed A. King, D. Ryan Veeraraghavan, Rengasayee Gourdie, Robert G. Baker, Joseph W. Arnold, William S. AlMahameed, Soufian T. Poelzing, Steven Front Physiol Physiology Aims: Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous evidence in animal models suggests that the gap junction (GJ) adjacent nanodomain – perinexus – is a site capable of independent intercellular communication via ephaptic transmission. Perinexal expansion is associated with slowed conduction and increased ventricular arrhythmias in animal models, but has not been studied in human tissue. The purpose of this study was to characterize the perinexus in humans and determine if perinexal expansion associates with AF. Methods: Atrial appendages from 39 patients (pts) undergoing cardiac surgery were fixed for immunofluorescence and transmission electron microscopy (TEM). Intercalated disk distribution of the cardiac sodium channel Nav1.5, its β1 subunit, and connexin43 (C×43) was determined by confocal immunofluorescence. Perinexal width (Wp) from TEM was manually segmented by two blinded observers using ImageJ software. Results: Nav1.5, β1, and C×43 are co-adjacent within intercalated disks of human atria, consistent with perinexal protein distributions in ventricular tissue of other species. TEM revealed that the GJ adjacent intermembrane separation in an individual perinexus does not change at distances greater than 30 nm from the GJ edge. Importantly, Wp is significantly wider in patients with a history of AF than in patients with no history of AF by approximately 3 nm, and Wp correlates with age (R = 0.7, p < 0.05). Conclusion: Human atrial myocytes have voltage-gated sodium channels in a dynamic intercellular cleft adjacent to GJs that is consistent with previous descriptions of the perinexus. Further, perinexal width is greater in patients with AF undergoing cardiac surgery than in those without. Frontiers Media S.A. 2018-05-04 /pmc/articles/PMC5945828/ /pubmed/29780324 http://dx.doi.org/10.3389/fphys.2018.00398 Text en Copyright © 2018 Raisch, Yanoff, Larsen, Farooqui, King, Veeraraghavan, Gourdie, Baker, Arnold, AlMahameed and Poelzing. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Raisch, Tristan B.
Yanoff, Matthew S.
Larsen, Timothy R.
Farooqui, Mohammed A.
King, D. Ryan
Veeraraghavan, Rengasayee
Gourdie, Robert G.
Baker, Joseph W.
Arnold, William S.
AlMahameed, Soufian T.
Poelzing, Steven
Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation
title Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation
title_full Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation
title_fullStr Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation
title_full_unstemmed Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation
title_short Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation
title_sort intercalated disk extracellular nanodomain expansion in patients with atrial fibrillation
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945828/
https://www.ncbi.nlm.nih.gov/pubmed/29780324
http://dx.doi.org/10.3389/fphys.2018.00398
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