Article Type: Research Article Article Citation: Abrahám A. Embí BS MBA. (2020). GLYCOGEN AND
ATRIAL FIBRILLATION ATRIAL MYOCYTES CONTRACTILITY AS MECHANICAL FACTOR SHIFTING
INTRACELLULAR GLYCOGEN AGAINST INTERCALATED DISCS. International Journal of
Research -GRANTHAALAYAH, 8(11), 106-111. https://doi.org/10.29121/granthaalayah.v8.i11.2020.2075 Received Date: 01 November 2020 Accepted Date: 30 November 2020 Keywords: Atrial Fibrillation Glycogen Gap Junctions Atrial Contractility Gap Junction Blockage Genesis Atrial Fibrillation The purpose of this communication is to introduce in the medical literature an additional factor until now hypothesized action of atrial cells depolarization as factor in intracellular flow of glycogen molecules coalescing against the gap junctions. The demonstrated effect of gap junction blockers on paired cells contractility combined with gap junction’s selectivity towards glycogen molecules; and the visualization of contrasting intracellular glycogen images during atrial fibrillation are shown. Published data supporting atrial myocytes contraction as a mechanism in intracellular glycogen molecules migration and its deleterious effects leading into atrial fibrillation (AF) is proposed.
1. INTRODUCTIONIn a previous publication in 2014, we show that in atrial myocytes glycogen
is heterogeneously distributed in both atria in the normal goat heart; however,
in AF the density of glycogen deposits concentrating against the intercalated
discs and side to side connections in the left atrial appendage is a critically
distinct difference. Impediment of cell to cell conduction could result in a non-uniform wavefront of activation, with areas
of slowed conduction, predisposing the left atrium to reentrant based atrial
fibrillation” [1]. 2.
MATERIALS AND METHODS
A literature search was conducted relevant to changes in
atrial myocytes architecture, with specific emphasis in the effect of myocytes
intercellular gap junction blockage, such as from glycogen molecules which has
been previously hypothesized as additional factor in the genesis of atrial
fibrillation (AF). 3.
RESULTS
3.1. ATRIAL DEPOLARIZATION AND GAP JUNCTION
BLOCKAGE IN LONGITUDINALLY CONNECTED CELLS
Published data presented now supports the physical force
transduction by atrial intracellular depolarization as a primary factor in
glycogen molecules accumulating against intercalated discs and causing
deleterious effects in cell contractility. The following publication and image
were found where a micro device designed for the study of intercellular
electromechanical force transduction [2] between atrial
myocytes, shows the effect of gap junction blockage on intercellular atrial
cell contractility [3], as shown in
Exhibit 1 below. EXHIBIT 1 Above figure reproduced and credit given to: Zhang, X., Wang, Q., Gablaski, B.,
Zhang, X., Lucchesi, P., & Zhao, Y. (2013). A microdevice for studying
intercellular electromechanical transduction in adult cardiac myocytes. Lab on a chip, 13(15), 3090–3097. https://doi.org/10.1039/c3lc50414j 3.2. UNPUBLISHED
IMAGE OF CONTRASTING GLYCOGEN AND GAP JUNCTION BLOCKAGE
The second relevant finding was an unpublished image, albeit
used in a university setting Medical Grand Rounds from in vivo experiments showing glycogen molecules blocking dog’s
atrial myocytes in experimentally induced AF. Tissue biopsy was obtained in vivo during induced AF by rapid
atrial pacing. The sample then stained using Periodic acid–Schiff (PAS) that is a staining method
used to detect polysaccharides such as glycogen. This image was included in a slide at The University of Oklahoma Medical Grand Rounds in May 2014 entitled “Fact: Atrial Fibrillation is the Most Common Clinical (Sustained) Cardiac Arrhythmia: What are the Factors *Underlying [4] (Exhibits 2,3). EXHIBIT 2
Grand Rounds Presentation Title at University of Oklahoma (May 2014) EXHIBIT 3
Figure Unpublished image showing glycogen molecules coalescing against intercalated discs during AF. Tissue sample obtained from the dog Left Atrial Appendage during atrial fibrillation. Black Arrows: Pointing at myocytes intercalated discs. Notice the stained glycogen molecules delineating the discs and theorized to be as result of cellular contraction internal forces. This phenomenon is introduced as additional factor affecting intra atrial electrical conduction. Orange Arrows: Indicating opposite direction of myocytes depolarization or contraction during AF. Note: Image of tissue obtained, thus remaining unpublished in the medical literature; but presented at Medical Grand Rounds at the University of Oklahoma USA, (May 2014). 3.3. INTRACELLULAR
GLYCOGEN AND CENTRIFUGAL FORCES THE MUIR’S EXPERIMENTS (1965)
In a paper
published in 1965 non-contractile sheep Purkinje cells were subjected to
centrifugal forces prior to fixation as shown in Exhibit 1 below. Only the
centrifuged conducting cells show glycogen molecules unable to penetrate and
coalescing at the gap junctions (Exhibit 4). In contrast, non-centrifuged
control conducting cells show a homogeneous distribution of glycogen. EXHIBIT 4
Heart Sheep: In vitro demonstration of gap junction
selectivity towards the glycogen molecules. Figure 1. Purkinge Fibers after
centrifugation. Notice the presence of the stained glycogen concentrating
against the gap intercellular intercalated discs gap junction. Purkinje cell
are reported to have a higher density of pores that the atrial myocytes.
Selectivity towards molecular size is clearly demonstrated. (Arrow denotes
centrifugal force) Figure 1: Post Centrifugal
Force. Amplified with labels. Figure 2: Control experiment.
Amplified with labels. All above Images printed with permission from publisher: Muir AR. Further observations on the cellular structure of cardiac muscle JAnat Lond 1965;99:27-46. 4. DISCUSSIONAtrial Myocytes structural changes in the progression of
atrial fibrillation, and the potential role of glycogen and fibrosis as
perpetuating factors have been proposed [5]. The data
presented in this manuscript supports atrial myocytes contractility as a
primary factor in causing glycogen blockage of gap junctions and side by side
connections. As concluded by Zangh et al [5]. “The differential in glycogen
concentration, in conjunction with other factors, neural and
electrophysiological, provide a basis for the greater propensity of the left
atrium for paroxysmal AF, at baseline and 48 hours of pacing induced AF. The
marked increase in collagen at 8 weeks of pacing provides a substrate for
sustained AF. Evidence is presented linking glycogen accumulation and fibrosis
as factors in the persistent forms of AF”. Contractile cells such as atrial or Ventricular myocytes; and
constitute 99% of the myocardial tissue, whereas the remainder 1% conducting
cells form the heart electrical conducting system, such as Purkinje cells.
Relevant to this commentary is that Purkinje cells are much smaller “than the
contractile cells and have few of the myofibrils or filaments needed for
contraction. Their function is similar in many respects to neurons” [7]. In other words,
cardiac conducting cells are non-contractile; instead they serve as a conduit
to propagate electrical impulses and initiating contractions of the abundant
contractile cells. In this manuscript we are introducing a new insight in the
genesis of AF, this being the contractile myocytes as causing intracellular
glycogen molecules to coalesce against the intercalated discs and side by side
cellular connections. The mechanical intracellular atrial contractility forces
exerted on the glycogen molecules is supported by the analogy of centrifugation
in the Muir’s experiments. How to counteract the consequences of this
phenomenon are in need of further research. 5.
CONCLUSSIONS
In contractile cardiac cells, such as atrial myocytes, depolarization mechanical transduction is identified as factor for intracellular glycogen molecules blocking intercellular communication. SOURCES OF FUNDINGThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. CONFLICT OF INTERESTThe author have declared that no competing interests exist. ACKNOWLEDGMENTNone. REFERENCES
[6]
Muir AR.
Further observations on the cellular structure of cardiac muscle JAnat Lond
1965; 99:27-4
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