From myofibril to membrane; the transitional junction at the intercalated disc

10.2741/3972 ◽  
2012 ◽  
Vol 17 (1) ◽  
pp. 1035 ◽  
Author(s):  
Pauline, M Bennett
Keyword(s):  
Intercalated Disc ◽  
Transitional Junction

scholarly journals The Transitional Junction: A New Functional Subcellular Domain at the Intercalated Disc

2006 ◽  
Vol 17 (4) ◽  
pp. 2091-2100 ◽  
Author(s):  
Pauline M. Bennett ◽  
Alison M. Maggs ◽  
Anthony J. Baines ◽  
Jennifer C. Pinder
Keyword(s):  
Plasma Membrane ◽  
Adherens Junction ◽  
Immunogold Electron Microscopy ◽  
Contractile Apparatus ◽  
Intercalated Disc ◽  
Structural Element ◽  
Thin Filaments ◽  
Rich Domain ◽  
Muscle Plasma Membrane ◽  
Transitional Junction

We define here a previously unrecognized structural element close to the heart muscle plasma membrane at the intercalated disc where the myofibrils lead into the adherens junction. At this location, the plasma membrane is extensively folded. Immunofluorescence and immunogold electron microscopy reveal a spectrin-rich domain at the apex of the folds. These domains occur at the axial level of what would be the final Z-disc of the terminal sarcomere in the myofibril, although there is no Z-disc-like structure there. However, a sharp transitional boundary lies between the myofibrillar I-band and intercalated disc thin filaments, identifiable by the presence of Z-disc proteins, α-actinin, and N-terminal titin. This allows for the usual elastic positioning of the A-band in the final sarcomere, whereas the transduction of the contractile force normally associated with the Z-disc is transferred to the adherens junctions at the plasma membrane. The axial conjunction of the transitional junction with the spectrin-rich domains suggests a mechanism for direct communication between intercalated disc and contractile apparatus. In particular, it provides a means for sarcomeres to be added to the ends of the cells during growth. This is of particular relevance to understanding myocyte elongation in dilated cardiomyopathy.

Morphologic and pathologic aspect of intercalated disc of the heart

1969 ◽  
Vol 78 (3) ◽  
pp. 358-368 ◽  
Author(s):  
G.E. Burch ◽  
R.S. Sohal
Keyword(s):  
Intercalated Disc

scholarly journals Cytochemical localization of a "basic" ATPase to canine myocardial surface membrane.

1980 ◽  
Vol 28 (12) ◽  
pp. 1286-1294 ◽  
Author(s):  
N N Malouf ◽  
G Meissner
Keyword(s):  
Cardiac Muscle ◽  
Microsomal Fraction ◽  
Surface Membrane ◽  
Buoyant Density ◽  
Membrane Structures ◽  
Intercalated Disc ◽  
Cytochemical Localization ◽  
Fixed Tissue ◽  
T System

Enzymatic properties of a canine cardiac muscle microsomal fraction were determined to localize in situ a "basic," divalent cation dependent adenosine triphosphatase (ATPase) by ultrastructural cytochemistry. The microsomal fraction had a buoyant density of 1.08--1.13 (20--30% [w/w] sucrose) and hydrolyzed adenosine triphosphate in the presence of Mg2+, Ca2+, Mn2+, or Co2+, but not in that of Sr2+ or Ni2+, under conditions that inhibited interfering (Na+ + K+)-ATPase and sarcoplasmic reticulum Ca2+-ATPase activities. "Basic" ATPase was localized in paraformaldehyde-fixed tissue in a medium containing Mg2+ or a high Ca2+ concentration (4 mM). A free Pb2+ concentration of less than 1 microM was used to capture enzymatically released phosphate anions. Electron-dense lead precipitates were present at the plasmalemma, T-system, and intercalated disc membranes with the exception of the nexus. These studies suggest that "basic" ATPase activity is associated with surface membrane structures of canine cardiac muscle.

scholarly journals Myozap, a Novel Intercalated Disc Protein, Activates Serum Response Factor–Dependent Signaling and Is Required to Maintain Cardiac Function In Vivo

2010 ◽  
Vol 106 (5) ◽  
pp. 880-890 ◽  
Author(s):  
Thalia S. Seeger ◽  
Derk Frank ◽  
Claudia Rohr ◽  
Rainer Will ◽  
Steffen Just ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Serum Response Factor ◽  
Response Factor ◽  
Intercalated Disc ◽  
Serum Response

scholarly journals Induced Deletion of theN-CadherinGene in the Heart Leads to Dissolution of the Intercalated Disc Structure

2005 ◽  
Vol 96 (3) ◽  
pp. 346-354 ◽  
Author(s):  
Igor Kostetskii ◽  
Jifen Li ◽  
Yanming Xiong ◽  
Rong Zhou ◽  
Victor A. Ferrari ◽  
...  
Keyword(s):  
Intercalated Disc

scholarly journals P414Cardiac pacing modifies connexin43 localization within the intercalated disc during ischaemia, 24h later

2014 ◽  
Vol 103 (suppl 1) ◽  
pp. S76.3-S76
Author(s):  
M Kovacs ◽  
T Kun ◽  
M Gonczi ◽  
G Miskolczi ◽  
GY Seprenyi ◽  
...  
Keyword(s):  
Intercalated Disc

Carbon nanotubes enhance intercalated disc assembly in cardiac myocytes via the β1-integrin-mediated signaling pathway

Biomaterials ◽  
2015 ◽  
Vol 55 ◽  
pp. 84-95 ◽  
Author(s):  
Hongyu Sun ◽  
Shuanghong Lü ◽  
Xiao-Xia Jiang ◽  
Xia Li ◽  
Hong Li ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Signaling Pathway ◽  
Cardiac Myocytes ◽  
Β1 Integrin ◽  
Intercalated Disc

Abstract MP216: Identification Of Novel Phosphoprotein Signaling Pathways In Human Dilated Cardiomyopathy By Integrative Proteomic And Phosphoproteomic Analysis

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Cristine J Reitz ◽  
Marjan Tavassoli ◽  
Da Hye Kim ◽  
Sina Hadipour-Lakmehsari ◽  
Saumya Shah ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Cardiac Tissue ◽  
Regulatory Element ◽  
Critical Role ◽  
Left Ventricular ◽  
Confocal Imaging ◽  
Intercalated Disc ◽  
Bioinformatics Analyses ◽  
Tissue Samples ◽  
And Function

Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure, yet the majority of the underlying signaling mechanisms remain poorly characterized. Protein phosphorylation is a key regulatory element with profound effects on the activity and function of signaling networks; however, there is a lack of comprehensive phosphoproteomic studies in human DCM patients. We assessed the hypothesis that an integrative phosphoproteomics analysis of human DCM would reveal novel phosphoprotein candidates involved in disease pathophysiology. Combined proteomic and phosphoproteomic analysis of explanted left ventricular tissue samples from DCM patients ( n =4) and non-failing controls ( n =4) identified 5,570 unique proteins with 13,624 corresponding phosphorylation sites. From these analyses, we identified αT-catenin as a unique candidate protein with a cluster of 4 significantly hyperphosphorylated sites in DCM hearts ( P <0.0001), with no change in total αT-catenin expression at the protein level. Bioinformatics analyses of human datasets and confocal imaging of human and mouse cardiac tissue show highly cardiac-enriched expression of αT-catenin, localized to the cardiomyocyte intercalated disc. High resolution 3-dimensional reconstruction shows elongated intercalated disc morphology in DCM hearts (10.07±0.76 μm in controls vs. 17.20±1.87 μm in DCM, P <0.05, n =3/group), with significantly increased colocalization of αT-catenin with the intercalated disc membrane protein N-cadherin (Pearson’s coefficient 0.55±0.04 in controls vs. 0.71±0.02 in DCM, P <0.05, n =3/group). To investigate the functional role of cardiac αT-catenin phosphorylation, we overexpressed WT protein vs. non-phosphorylatable forms based on the loci identified in DCM hearts, in adult mouse cardiomyocytes using lentiviral transduction. Confocal imaging revealed significant internalization of the phospho-null form, as compared to the prominent intercalated disc staining of the WT protein (17.78±0.79% of WT vs. 9.25±0.49% of 4A mutant, P <0.0001, n =50 cells/group). Together, these findings suggest a critical role for αT-catenin phosphorylation in maintaining cardiac intercalated disc organization in human DCM.

Hypernatremia and Intercalated Disc Edema Synergistically Exacerbate Long QT Syndrome Type 3 Phenotype

2021 ◽  
Author(s):  
Xiaobo Wu ◽  
Gregory S. Hoeker ◽  
Grace Blair ◽  
David Ryan King ◽  
Robert G. Gourdie ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sodium Concentration ◽  
Syndrome Type ◽  
Intercalated Disc ◽  
Long Qt ◽  
Disc Edema ◽  
Cardiac Edema ◽  
Qt Syndrome ◽  
Extracellular Sodium ◽  
Type 3

Background: Cardiac voltage-gated sodium channel gain-of-function prolongs repolarization in the Long-QT Syndrome Type 3 (LQT3). Previous studies suggest that narrowing the perinexus within the intercalated disc, leading to rapid sodium depletion, attenuates LQT3-associated action potential duration (APD) prolongation. However, it remains unknown whether extracellular sodium concentration modulates APD prolongation during sodium channel gain-of-function. We hypothesized that elevated extracellular sodium concentration and widened perinexus synergistically prolong APD in LQT3. Methods and Results: LQT3 was induced with anemone toxin type II (ATXII) in Langendorff-perfused guinea pig hearts (n=20). Sodium concentration was increased from 145 to 160 mM. Perinexal expansion was induced with mannitol or the sodium channel β1-subunit adhesion domain antagonist (βadp1). Epicardial ventricular action potentials were optically mapped. Individual and combined effects of varying clefts and sodium concentrations were simulated in a computational model. With ATXII, both mannitol and βadp1 significantly widened the perinexus and prolonged APD, respectively. The elevated sodium concentration alone significantly prolonged APD as well. Importantly, the combination of elevated sodium concentration and perinexal widening synergistically prolonged APD. Computational modeling results were consistent with animal experiments. Conclusions: Concurrently elevating extracellular sodium and increasing intercalated disc edema prolongs repolarization more than the individual interventions alone in the LQT3. This synergistic effect suggests an important clinical implication that hypernatremia in the presence of cardiac edema can markedly increase LQT3-associated APD prolongation. Therefore, this is the first study to provide evidence of a tractable and effective strategy to mitigate LQT3 phenotype by managing patient sodium levels and preventing cardiac edema.

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