Gap junctions–guards of excitability

2015 ◽  
Vol 43 (3) ◽  
pp. 508-512 ◽  
Author(s):  
Line Waring Stroemlund ◽  
Christa Funch Jensen ◽  
Klaus Qvortrup ◽  
Mario Delmar ◽  
Morten Schak Nielsen
Keyword(s):  
Sodium Channel ◽  
Crucial Role ◽  
Connexin 43 ◽  
Current Evidence ◽  
Intercalated Disc ◽  
Intercalated Discs ◽  
Cardiac Sodium Channel ◽  
Junctional Protein ◽  
Gap Junctional

Cardiomyocytes are connected by mechanical and electrical junctions located at the intercalated discs (IDs). Although these structures have long been known, it is becoming increasingly clear that their components interact. This review describes the involvement of the ID in electrical disturbances of the heart and focuses on the role of the gap junctional protein connexin 43 (Cx43). Current evidence shows that Cx43 plays a crucial role in organizing microtubules at the intercalated disc and thereby regulating the trafficking of the cardiac sodium channel NaV1.5 to the membrane.

scholarly journals P266Down regulation of the cardiac sodium channel Nav1.5 by the MAGUK protein CASK: role of its functional domains

2018 ◽  
Vol 114 (suppl_1) ◽  
pp. S68-S68
Author(s):  
A Beuriot ◽  
C Eichel ◽  
N Doisne ◽  
F Louault ◽  
A Coulombe ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Functional Domains ◽  
Cardiac Sodium Channel ◽  
Maguk Protein

Abstract 20627: Modulation of Cardiac Sodium Channel by Palmitoylation and Its Association With Cardiac Disease Mutations

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Zifan Pei ◽  
Andy Hudmon ◽  
Theodore R Cummins
Keyword(s):  
Steady State ◽  
Sodium Channel ◽  
Functional Activity ◽  
Site Directed Mutagenesis ◽  
Significant Shift ◽  
Biophysical Properties ◽  
Disease Mutations ◽  
Cardiac Sodium Channel ◽  
Steady State Inactivation

Cardiac sodium channel (Nav1.5) is responsible for the generation and propagation of the cardiac action potential, which underlies cardiac excitability. It can be modified by a variety of post-translational modifications. Palmitoylation is one of the most common post-translational lipid modifications that can dynamically regulate protein life cycle and functional activity. In our study, we identified palmitoylation on Nav1.5 and its alteration in channel biophysical properties. Nav1.5 palmitoylation was identified in both HEK 293 cells stably expressing Nav1.5 and cardiac tissues using acyl-biotin exchange assay. Nav1.5 palmitoylation was inhibited by pre-incubating the cells with the inhibitor 2-Br-Palmitate (2BP, 25uM, 24hrs). Biophysically, 2BP treatment drastically shifted the channel steady-state inactivation to more hyperpolarized voltages, suggesting palmitoylation altering channel functional activity. In addition, four predicted endogenous palmitoylation sites were identified using CSS-Palm 3.0. Site-directed mutagenesis method was used to generate a cysteine removing background of wt Nav1.5 to study the role of predicted sites. Patch clamp analysis of wt and cysteine-removed Nav1.5 revealed a significant change in channel biophysics. 2BP treatment significantly shifted steady-state inactivation of wt Nav1.5 while not affecting cysteine-removed Nav1.5 significantly, indicating the important role of these four cysteine sites in modulating channel palmitoylation. Moreover, several LQT disease mutations were identified to potentially add or remove palmitoylation sites. Further analysis of these disease mutations revealed a significant shift in channel steady-state inactivation and this alteration cannot be seen with the substitution of other residues on the same site, suggesting the specific role of cysteine residue in causing the functional alteration. For the LQT mutation that removes potential palmitoylation site, 2BP treatment did not affect channel biophysical properties, indicating the essential role of this cysteine in channel palmitoylation. These results suggest that palmitoylation on Nav1.5 regulates channel functional activity and its modulation may contribute to new cardiac channelopathies.

LM and EM immunolocalization of the gap junctional protein connexin 43 in rat brain

1990 ◽  
Vol 508 (2) ◽  
pp. 313-319 ◽  
Author(s):  
T. Yamamoto ◽  
A. Ochalski ◽  
E.L. Hertzberg ◽  
J.I. Nagy
Keyword(s):  
Rat Brain ◽  
Connexin 43 ◽  
Junctional Protein ◽  
Gap Junctional

scholarly journals The Role of Intestinal Permeability in Gastrointestinal Disorders and Current Methods of Evaluation

2021 ◽  
Vol 8 ◽  
Author(s):  
Tim Vanuytsel ◽  
Jan Tack ◽  
Ricard Farre
Keyword(s):  
Intestinal Permeability ◽  
Barrier Function ◽  
Crucial Role ◽  
Intestinal Barrier Function ◽  
Current Evidence ◽  
Gastrointestinal Disorders ◽  
Fatty Acid Binding ◽  
Ussing Chambers

An increased intestinal permeability has been described in various gastrointestinal and non-gastrointestinal disorders. Nevertheless, the concept and definition of intestinal permeability is relatively broad and includes not only an altered paracellular route, regulated by tight junction proteins, but also the transcellular route involving membrane transporters and channels, and endocytic mechanisms. Paracellular intestinal permeability can be assessed in vivo by using different molecules (e.g., sugars, polyethylene glycols, 51Cr-EDTA) and ex vivo in Ussing chambers combining electrophysiology and probes of different molecular sizes. The latter is still the gold standard technique for assessing the epithelial barrier function, whereas in vivo techniques, including putative blood biomarkers such as intestinal fatty acid-binding protein and zonulin, are broadly used despite limitations. In the second part of the review, the current evidence of the role of impaired barrier function in the pathophysiology of selected gastrointestinal and liver diseases is discussed. Celiac disease is one of the conditions with the best evidence for impaired barrier function playing a crucial role with zonulin as its proposed regulator. Increased permeability is clearly present in inflammatory bowel disease, but the question of whether this is a primary event or a consequence of inflammation remains unsolved. The gut-liver axis with a crucial role in impaired intestinal barrier function is increasingly recognized in chronic alcoholic and metabolic liver disease. Finally, the current evidence does not support an important role for increased permeability in bile acid diarrhea.

Role of Gap Junctional Protein Connexin40 in the Pathogenesis of Atrial Fibrillation

2000 ◽  
Vol 99 (s43) ◽  
pp. 8P-8P
Author(s):  
P Kanagaratnam ◽  
NJ Severs ◽  
NS Peters
Keyword(s):  
Atrial Fibrillation ◽  
Junctional Protein ◽  
Gap Junctional

Conservation of a cytoplasmic carboxy-terminal domain of connexin 43, a gap junctional protein, in mammal heart and brain

1990 ◽  
Vol 115 (3) ◽  
pp. 229-240 ◽  
Author(s):  
Abdelhakim El Aoumari ◽  
Catherine Fromaget ◽  
Emmanuel Dupont ◽  
Hubert Reggio ◽  
Pascale Durbec ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Junctional Protein ◽  
Carboxy Terminal ◽  
Gap Junctional
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