GLYCOGEN AND ATRIAL FIBRILLATION ATRIAL MYOCYTES CONTRACTILITY AS MECHANICAL FACTOR SHIFTING INTRACELLULAR GLYCOGEN AGAINST INTERCALATED DISCS

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INTRODUCTION
In 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].

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).

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.

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.

DISCUSSION
Atrial 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.

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 FUNDING
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.