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

2020 ◽  
Vol 8 (11) ◽  
pp. 106-111
Author(s):  
Abraham A. Embi
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junctions ◽  
Gap Junction ◽  
Medical Literature ◽  
Published Data ◽  
Atrial Myocytes ◽  
Mechanical Factor ◽  
Intercalated Discs ◽  
Atrial Cells

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.

The role of angiotensin in electrophysiological gap junction remodeling in human atrial fibrillation

2004 ◽  
Vol 52 (S 1) ◽  
Author(s):  
S Dhein ◽  
A Boldt ◽  
J Garbade ◽  
L Polontchouk ◽  
U Wetzel ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Human Atrial Fibrillation

Treatment with beta-blockers normalizes RyR2 phosphorylation and calcium spark activity in atrial myocytes from patients with atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Jimenez-Sabado ◽  
S Casabella ◽  
P Izquierdo ◽  
C Tarifa ◽  
A Llach ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Calcium Imaging ◽  
Adrenergic Receptors ◽  
Beta Blockers ◽  
Funding Source ◽  
Atrial Myocytes ◽  
Calcium Sparks ◽  
Beta Adrenergic ◽  
Calcium Spark ◽  
Confocal Calcium Imaging

Abstract Background Atrial fibrillation has been associated with an increase in ryanodine receptor (RyR2) phosphorylation and local calcium release (calcium sparks). Carvedilol, a nonselective beta-adrenergic receptor blocker also inhibits the cardiac ryanodine receptor (RyR2), but it has been suggested that the enantiomer R-carvedilol only inhibits RyR2 activity and hence has the potential to inhibit calcium sparks without affecting RyR2 phosphorylation. Purpose This study aimed to determine the ability of the enantiomers R- and S-carvedilol to reverse RyR2 phosphorylation at s2808 and calcium sparks induced by the β2-adrenergic agonist fenoterol, in order to determine the relationship between RyR2 phosphorylation at s2808 and calcium spark frequency, and to assess the efficacy of R- and S-carvedilol. Methods Human right atrial myocytes were isolated and subjected to immunofluorescent labelling of total and s2808 phosphorylated RyR2, or loaded with fluo-4 and subjected to confocal calcium imaging. Beta-adrenergic receptors were first activated with 3μM fenoterol and then inhibited by different concentrations of carvedilol R- or S-enantiomers. Results Incubation of myocytes with fenoterol increased the s2808/RyR2 ratio from 0.32±0.03 to 0.66±0.05 (n=18, p<0.001). Incubation with 0.1, 0.3, 1 or 3μM R-carvedilol in the presence of fenoterol changed the s2808/RyR2 ratio to 0.64±0.05, 0.44±0.04, 0.34±0.07 and 0.28±0.05 (p<0.01) respectively. For comparison 3μM S-carvedilol reduced the s2808/RyR2 ratio to 0.23±0.06 in myocytes from 5 patients (p<0.01). Confocal calcium imaging revealed that fenoterol increased the spark density from 0.28±0.04 to 1.24±0.25 events/s/1000μm2 (n=9, p<0.01) and addition of 0.1, 0.3, or 1μM R-carvedilol changed the frequency to 1.32±0.52, 0.38±0.05, and 0.15±0.05 events/s/1000μm2 (p<0.01) respectively. Analysis of atrial myocytes from patients without atrial fibrillation revealed that the s2808/RyR2 ratio was similar in 25 patients treated with beta-blockers (0.39±0.04) and 57 that did not receive beta-blockers (0.44±0.03, p=0.33) while the s2808/RyR2 ratio was significantly smaller in 16 patients with atrial fibrillation receiving beta-blockers (0.43±0.08) than in 5 patients that did not (0.80±0.19, p<0.05). Conclusions R-carvedilol reverses the effects of beta-adrenergic stimulation on s2808 phosphorylation and calcium sparks in human atrial myocytes, and treatment with beta-blockers reduces excessive RyR2 phosphorylation at s2808 in patients with atrial fibrillation to levels observed in those without the arrhythmia, pointing to beta-adrenergic receptors as a target for controlling RyR2 phophorylation and activity in atrial fibrillation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science and Innovation & Spanish Ministry of Health and Consume

scholarly journals Two Drosophila Innexins Are Expressed in Overlapping Domains and Cooperate to Form Gap-Junction Channels

2000 ◽  
Vol 11 (7) ◽  
pp. 2459-2470 ◽  
Author(s):  
Lucy A. Stebbings ◽  
Martin G. Todman ◽  
Pauline Phelan ◽  
Jonathan P. Bacon ◽  
Jane A. Davies
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Ectopic Expression ◽  
In Vivo Studies ◽  
Electrophysiological Properties ◽  
Gap Junction Channels ◽  
Overlapping Domains ◽  
In Vitro Data

Members of the innexin protein family are structural components of invertebrate gap junctions and are analogous to vertebrate connexins. Here we investigate two Drosophila innexin genes,Dm-inx2 and Dm-inx3 and show that they are expressed in overlapping domains throughout embryogenesis, most notably in epidermal cells bordering each segment. We also explore the gap-junction–forming capabilities of the encoded proteins. In pairedXenopus oocytes, the injection of Dm-inx2mRNA results in the formation of voltage-sensitive channels in only ∼ 40% of cell pairs. In contrast, Dm-Inx3 never forms channels. Crucially, when both mRNAs are coexpressed, functional channels are formed reliably, and the electrophysiological properties of these channels distinguish them from those formed by Dm-Inx2 alone. We relate these in vitro data to in vivo studies. Ectopic expression ofDm-inx2 in vivo has limited effects on the viability ofDrosophila, and animals ectopically expressingDm-inx3 are unaffected. However, ectopic expression of both transcripts together severely reduces viability, presumably because of the formation of inappropriate gap junctions. We conclude that Dm-Inx2 and Dm-Inx3, which are expressed in overlapping domains during embryogenesis, can form oligomeric gap-junction channels.

Freeze-fracture studies of frog atrial fibres

1976 ◽  
Vol 22 (2) ◽  
pp. 427-434
Author(s):  
F. Mazet ◽  
J. Cartaud
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Outer Membrane ◽  
Electrical Coupling ◽  
Freeze Fracture ◽  
Present Knowledge ◽  
Inner Membrane ◽  
Freeze Fracturing ◽  
Morphological Variant ◽  
Characteristic Features

The freeze-fracturing technique was used to characterize the junctional devices involved in the electrical coupling of frog atrial fibres. These fibres are connected by a type of junction which can be interpreted as a morphological variant of the “gap junction” or “nexus”. The most characteristic features are rows of 9-nm junctional particles forming single or anastomosed circular profiles on the inner membrane face, and corresponding pits on the outer membrane face. Very seldom aggregates consisting of few geometrically disposed 9-nm particles are found. The significance of the junctional structures in the atrial fibres is discussed, with respect to present knowledge about junctional features of gap junctions in various tissues, including embryonic ones.

Investigation of the roles of Ca2+ and InsP3 diffusion in the coordination of Ca2+ signals between connected hepatocytes

2001 ◽  
Vol 114 (11) ◽  
pp. 1999-2007
Author(s):  
Caroline Clair ◽  
Cécile Chalumeau ◽  
Thierry Tordjmann ◽  
Josiane Poggioli ◽  
Christophe Erneux ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Significant Role ◽  
Signaling Molecules ◽  
Rat Hepatocyte ◽  
Inositol 1,4,5 Trisphosphate ◽  
Gap Junction Coupling ◽  
Junction Coupling ◽  
Insp3 Receptor

Glycogenolytic agonists induce coordinated Ca2+ oscillations in multicellular rat hepatocyte systems as well as in the intact liver. The coordination of intercellular Ca2+ signals requires functional gap-junction coupling. The mechanisms ensuring this coordination are not precisely known. We investigated possible roles of Ca2+ or inositol 1,4,5-trisphosphate (InsP3) as a coordinating messengers for Ca2+ spiking among connected hepatocytes. Application of ionomycin or of supra-maximal concentrations of agonists show that Ca2+ does not significantly diffuse between connected hepatocytes, although gap junctions ensure the passage of small signaling molecules, as demonstrated by FRAP experiments. By contrast, coordination of Ca2+ spiking among connected hepatocytes can be favored by a rise in the level of InsP3, via the increase of agonist concentrations, or by a shift in the affinity of InsP3 receptor for InsP3. In the same line, coordination cannot be achieved if the InsP3 is rapidly metabolized by InsP3-phosphatase in one cell of the multiplet. These results demonstrate that even if small amounts of Ca2+ diffuse across gap junctions, they most probably do not play a significant role in inducing a coordinated Ca2+ signal among connected hepatocytes. By contrast, coordination of Ca2+ oscillations is fully dependent on the diffusion of InsP3 between neighboring cells.

scholarly journals Gap junction structures after experimental alteration of junctional channel conductance.

1985 ◽  
Vol 101 (5) ◽  
pp. 1741-1748 ◽  
Author(s):  
T M Miller ◽  
D A Goodenough
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Electron Micrographs ◽  
Time Course ◽  
Structural Changes ◽  
Lucifer Yellow ◽  
Freeze Fracture ◽  
Channel Conductance ◽  
Experimental Alteration ◽  
Quick Freezing

Gap junctions are known to present a variety of different morphologies in electron micrographs and x-ray diffraction patterns. This variation in structure is not only seen between gap junctions in different tissues and organisms, but also within a given tissue. In an attempt to understand the physiological meaning of some aspects of this variability, gap junction structure was studied following experimental manipulation of junctional channel conductance. Both physiological and morphological experiments were performed on gap junctions joining stage 20-23 chick embryo lens epithelial cells. Channel conductance was experimentally altered by using five different experimental manipulations, and assayed for conductance changes by observing the intercellular diffusion of Lucifer Yellow CH. All structural measurements were made on electron micrographs of freeze-fracture replicas after quick-freezing of specimens from the living state; for comparison, aldehyde-fixed specimens were measured as well. Analysis of the data generated as a result of this study revealed no common statistically significant changes in the intrajunctional packing of connexons in the membrane plane as a result of experimental alteration of junctional channel conductance, although some of the experimental manipulations used to alter junctional conductance did produce significant structural changes. Aldehyde fixation caused a dramatic condensation of connexon packing, a result not observed with any of the five experimental uncoupling conditions over the 40-min time course of the experiments.

Control of gap junction formation in canine trachea by arachidonic acid metabolites

1986 ◽  
Vol 250 (3) ◽  
pp. C495-C505 ◽  
Author(s):  
R. Agrawal ◽  
E. E. Daniel
Keyword(s):  
Arachidonic Acid ◽  
Gap Junctions ◽  
Gap Junction ◽  
Direct Effects ◽  
Leukotriene C4 ◽  
Lipoxygenase Pathway ◽  
Junction Formation ◽  
Acid Metabolites ◽  
Pg E2

This study examined whether the synthesis of the metabolites of arachidonic acid (AA) was involved in gap junction formation by 4-aminopyridine (4-AP) treatment in vitro in canine trachealis. Studies were made of the effects on gap junction formation of putative inhibitors of the cyclooxygenase and of both this and the lipoxygenase pathway of AA metabolism and the direct effects of prostaglandins (PG) E2 and I2. The number of gap junctions of similar size was increased after brief exposure to 4-AP. After indomethacin (IDM), 4-AP treatment decreased the number of gap junctions but did not affect their size. Pretreatment with 5,8,11,14-eicosatetraynoic acid or nordihydroguiaretic acid, putative inhibitors of cyclooxygenase and lipoxygenase enzymes, inhibited both the 4-AP-induced increase and decrease in the number of gap junctions. FPL 55712, a putative antagonist of leukotriene C4, did not alter either the number or the size of gap junctions when added alone or in combination with IDM. AA alone increased the number of gap junctions, but after IDM, AA decreased the number of gap junctions compared with the controls. Incubation of trachealis strips in vitro for 30 min with PGE2 increased the number of gap junctions by about threefold along with an increase in the size of the gap junctions. Similar incubation with PGI2, however, increased the number of gap junctions by approximately 60% without any change in the size. In the course of some control experiments, an interaction between carbachol and alcohol was observed such that alcohol caused an IDM-sensitive relaxation of carbachol-induced contractions, which was not observed when serotonin was the contractile agent. These results strongly suggest that PGE2 and PGI2 increase the formation of gap junctions in canine trachealis and that these prostanoids are released by 4-AP treatment. Leukotrienes may also be inhibitory in the formation of gap junctions, but FPL 55712 did not affect either the increase or the decrease in gap junctions after 4-AP.

scholarly journals Anticoagulation for atrial fibrillation after intracranial hemorrhage

2018 ◽  
Vol 8 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Maximiliano A. Hawkes ◽  
Alejandro A. Rabinstein
Keyword(s):  
Atrial Fibrillation ◽  
Published Data ◽  
Review Of The Literature ◽  
Primary Event ◽  
Net Benefit ◽  
Nonvalvular Atrial Fibrillation ◽  
Letters To The Editor ◽  
Factors Associated ◽  
Randomized Controlled ◽  
Primary Endpoints

BackgroundWe summarize the existing evidence on the potential benefit of oral anticoagulation (OAC) in intracerebral hemorrhage (ICH) survivors with nonvalvular atrial fibrillation (NVAF).MethodsSystematic review of the literature to address the following issues: (1) prevalence of NVAF in ICH survivors, (2) current prescription of OAC, (3) factors associated with resumption of OAC, (4) risk of ischemic stroke (IS) and recurrent ICH, and (5) ideal timing for restarting OAC in ICH survivors with NVAF.ResultsAfter screening 547 articles, 26 were included in the review. Only 3 focused specifically on patients with ICH as primary event, NVAF as indication for OAC, and recurrent ICH and IS as primary endpoints. In addition, 19 letters to the editor/reviews/editorials/experts' surveys/experts' opinion were used for discussion purposes.ConclusionsNVAF is highly prevalent among ICH survivors. The risks of IS, recurrent ICH, and mortality are heightened in this group. Most published data show a net benefit in terms of IS prevention and mortality when anticoagulation is restarted. However, those studies are observational and mostly retrospective, therefore selection bias may play a major role in the results observed in these cohorts. Only randomized controlled trials, either pragmatic or explanatory, can provide more conclusive answers for this important clinical question.

Abstract 84: Atrial Fibrillation Causes a Progressive, Time-Dependent Reduction in Myocardial Neuronal NOS in Humans and Goats: Implications for AF-Induced Electrical Remodeling

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Svetlana Reilly ◽  
Xing Liu ◽  
Raja Jayaram ◽  
Sunder Verheule ◽  
Uli Schotten ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Electrical Properties ◽  
Tissue Concentration ◽  
Specific Effect ◽  
Right Atrial ◽  
Early Event ◽  
Atrial Myocytes ◽  
History Of ◽  
Neuronal Nos ◽  
The Difference

Rationale: Nitric oxide (NO) plays a key role in the regulation of cardiac and endothelial function and thrombogenesis. Atrial fibrillation (AF) has been associated with reduced NO availability but the mechanisms and implications of this finding remain to be fully investigated. Methods and Results: We evaluated NO synthase (NOS) activity and localization in right atrial (RA) tissue from 30 patients with permanent AF (vs. 65 controls in sinus rhythm, SR), and in the RA and left atrial (LA) tissue of 48 goats after 2 weeks (2W) and 6 months (6M) of pacing-induced AF. NOS activity was uncoupled in RA tissue from patients and goats in 6M-AF, and was caused by a reduction in BH4 tissue concentration and by an increase in arginase activity (HPLC). Although BH4 and arginine supplementation re-coupled NOS, it did not abolish the difference in NOS activity between AF and SR. Immunoblotting and immunolocalization revealed a progressive reduction in bi-atrial neuronal NOS (nNOS) protein with the duration of AF (by 65% at 2W, 86% at 6M in goats and by 62% in patients with AF) and a reduction in eNOS in long-standing AF. nNOS was reduced in atrial myocytes but not in neuronal tissue. The mRNA expression of NOS (qRT-PCR) was unaltered; however, the reduction in nNOS protein in AF was associated with an increase in nNOS ubiquitination which was partially reversed by inhibition of proteosomal activity with MG132; inhibition of the autophagy-lysosomal pathway with bafilomycin A1 did not restore nNOS protein. To investigate the electrophysiological consequences of a reduced nNOS in LA and RA myocytes, we compared electrical properties of the isolated atrial myocytes from nNOS-/- mice (n=18) and their wild type (WT) littermates after nNOS inhibition with SMTC. Both nNOS gene deletion and inhibition impaired myocytes' relaxation in both RA and LA, and result in a slower rate of decay of [Ca2+]i transient in the LA myocytes only. Conclusions: A reduction in bi-atrial nNOS activity and protein level is an early event in the natural history of AF that results in a chamber-specific effect on electrical properties of the myocytes.

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