Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation

Frontiers in Physiology
Tristan B RaischSteven Poelzing

Abstract

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...Continue Reading

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Oct 13, 2018·Nature Reviews. Drug Discovery·Dale W Laird, Paul D Lampe
Jul 8, 2020·Biomolecules·Samantha C SalvageAntony P Jackson
Jul 18, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Gregory S HoekerSteven Poelzing
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Mar 5, 2021·Pflügers Archiv : European journal of physiology·D Ryan KingSteven Poelzing
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Sep 24, 2021·The Journal of Physiology·Rengasayee VeeraraghavanSeth H Weinberg
Oct 9, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Xiaobo WuSteven Poelzing
Dec 11, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Kiran Haresh Kumar PatelFu Siong Ng

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Methods Mentioned

BETA
transmission electron microscopy

Software Mentioned

ImageJ

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