scholarly journals The dual effect of ephaptic coupling on cardiac conduction with heterogeneous expression of connexin 43

2016 ◽  
Vol 397 ◽  
pp. 103-114 ◽  
Author(s):  
Ning Wei ◽  
Yoichiro Mori ◽  
Elena G. Tolkacheva
Keyword(s):  
Connexin 43 ◽  
Cardiac Conduction ◽  
Dual Effect ◽  
Heterogeneous Expression ◽  
Ephaptic Coupling

scholarly journals Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Parveen Sharma ◽  
Cynthia Abbasi ◽  
Savo Lazic ◽  
Allen C. T. Teng ◽  
Dingyan Wang ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Cardiac Conduction ◽  
Intercalated Disc ◽  
Evolutionarily Conserved

scholarly journals Cardiomyocyte Expression of ZO-1 Is Essential for Normal Atrioventricular Conduction but Does Not Alter Ventricular Function

2020 ◽  
Vol 127 (2) ◽  
pp. 284-297 ◽  
Author(s):  
Jianlin Zhang ◽  
Kevin P. Vincent ◽  
Angela K. Peter ◽  
Matthew Klos ◽  
Hongqiang Cheng ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Optical Mapping ◽  
Physiological Role ◽  
Cardiac Conduction ◽  
Scaffolding Protein ◽  
Surface Ecg ◽  
Associated Proteins ◽  
And Function ◽  
Nodal Tissue ◽  
Intact Heart

Rationale: ZO-1 (Zonula occludens-1), a plasma membrane-associated scaffolding protein regulates signal transduction, transcription, and cellular communication. Global deletion of ZO-1 in the mouse is lethal by embryonic day 11.5. The function of ZO-1 in cardiac myocytes (CM) is largely unknown. Objective: To determine the function of CM ZO-1 in the intact heart, given its binding to other CM proteins that have been shown instrumental in normal cardiac conduction and function. Methods and Results: We generated ZO-1 CM-specific knockout (KO) mice using α-Myosin Heavy Chain-nuclear Cre (ZO-1cKO) and investigated physiological and electrophysiological function by echocardiography, surface ECG and conscious telemetry, intracardiac electrograms and pacing, and optical mapping studies. ZO-1cKO mice were viable, had normal Mendelian ratios, and had a normal lifespan. Ventricular morphometry and function were not significantly different between the ZO-1cKO versus control (CTL) mice, basally in young or aged mice, or even when hearts were subjected to hemodynamic loading. Atrial mass was increased in ZO-1cKO. Electrophysiological and optical mapping studies indicated high-grade atrioventricular (A-V) block in ZO-1cKO comparing to CTL hearts. While ZO-1-associated proteins such as vinculin, connexin 43, N-cadherin, and α-catenin showed no significant change with the loss of ZO-1, Connexin-45 and Coxsackie-adenovirus (CAR) proteins were reduced in atria of ZO-1cKO. Further, with loss of ZO-1, ZO-2 protein was increased significantly in ventricular CM in a presumed compensatory manner but was still not detected in the AV nodal myocytes. Importantly, the expression of the sodium channel protein NaV1.5 was altered in AV nodal cells of the ZO-1cKO versus CTL. Conclusions: ZO-1 protein has a unique physiological role in cardiac nodal tissue. This is in alignment with its known interaction with CAR and Cx45, and a new function in regulating the expression of NaV1.5 in AV node. Uniquely, ZO-1 is dispensable for function of the working myocardium.

Heterogeneous expression of connexin 43 in the myocardium of rabbit right ventricular outflow tract

Life Sciences ◽  
2005 ◽  
Vol 77 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Baiqing Ou ◽  
Mikiko Nakagawa ◽  
Munetaka Kajimoto ◽  
Seiki Nobe ◽  
Tatsuhiko Ooie ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Connexin 43 ◽  
Right Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Outflow Tract ◽  
Heterogeneous Expression

Abstract 253: HSPB7 is Required for Maintaining the Intercalated Disc Structure to Prevent Cardiac Conduction System Failure in Mouse

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Wern-Chir Liao ◽  
Liang-Yi Juo ◽  
Yen-Hui Chen ◽  
Yu-Ting Yan
Keyword(s):  
Heart Failure ◽  
Gap Junction ◽  
Connexin 43 ◽  
Adherens Junction ◽  
Small Heat Shock Protein ◽  
Cardiac Conduction ◽  
Nucleotide Polymorphisms ◽  
Intercalated Disc ◽  
Junction Protein ◽  
And Function

HSPB7 is belonged to small heat-shock protein (HSPB) family and considered to function as a co-chaperone, which prevents protein aggregation and maintains protein structure. Single-nucleotide polymorphisms of HSPB7 associated with sporadic cardiomyopathy and heart failure have been identified in human patients. Additionally, HSPB7 is constitutively expressed in heart and rapidly increased in blood plasma after myocardial infarction, suggesting a functional role in the heart. In this study, we found that HSPB7 is highly colocalized with N-cadherin during the assembly and maturation of intercalated disc, suggesting that HSPB7 may involve in organizing and maintaining the cardiac cytoarchitecture. To elucidate the physiological function of HSPB7 in the adult heart, we generated a cardiac-specific inducible HSPB7 knockout mouse. Ablation of HSPB7 in the cardiomyocyte rapidly leads to heart failure, abnormal conduction properties and sudden arrhythmias death. Loss of HSPB7 did not cause significant changes in the organization of contractile proteins in sarcomeres, whereas severe abnormality in the intercalated disc was detected. The expression of connexin 43, a gap-junction protein located at the intercalated disc, was downregulated in HSPB7 knockout cardiomyocytes. Mislocalizations of desmoplakin (desmosomal proteins), and N-cadherin (adherens junction proteins) were also observed in the HSPB7 CKO hearts. Furthermore, filamin C, the interaction protein of HSPB7, was mislocalized and aggregated in HSPB7 mutant cardiomyocytes. The expressivity of the phenotype in the HSPB7 CKO mice is similar to human arrhythmogenic cardiomyopathy patients. Conclusively, we provide the first study characterizing HSPB7 as an intercalated disc protein. Our findings demonstrate that HSPB7 plays an essential role to maintain the structure and function of gap-junction complexes and intercalated disc and has vital implications for human heart disease.

scholarly journals Microtubule cytoskeleton regulates Connexin 43 localization and cardiac conduction in cardiomyopathy caused by mutation in A-type lamins gene

2018 ◽  
Author(s):  
Coline Macquart ◽  
Rene Jüttner ◽  
Blanca Morales Rodriguez ◽  
Caroline Le Dour ◽  
Florence Lefebvre ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Cardiac Conduction ◽  
Microtubule Cytoskeleton

scholarly journals Attenuating loss of cardiac conduction during no-flow ischemia through changes in perfusate sodium and calcium

2020 ◽  
Vol 319 (2) ◽  
pp. H396-H409 ◽  
Author(s):  
Gregory S. Hoeker ◽  
Carissa C. James ◽  
Allison N. Tegge ◽  
Robert G. Gourdie ◽  
James W. Smyth ◽  
...  
Keyword(s):  
Adaptive Response ◽  
Cardiac Conduction ◽  
Acute Ischemia ◽  
Intercalated Disc ◽  
Ionic Concentrations ◽  
Arrhythmogenic Substrate ◽  
Acute Changes ◽  
Extracellular Sodium ◽  
Ephaptic Coupling ◽  
Ischemic Stress

Conduction slowing during acute ischemia creates an arrhythmogenic substrate. We have shown that extracellular ionic concentrations can alter conduction by modulating ephaptic coupling. Here, we demonstrate increased extracellular sodium and calcium significantly attenuate conduction slowing during no-flow ischemia. This effect was associated with selective widening of the perinexus, an intercalated disc nanodomain and putative cardiac ephapse. These findings suggest that acute changes in ephaptic coupling may serve as an adaptive response to ischemic stress.

scholarly journals The adhesion function of the sodium channel beta subunit (β1) contributes to cardiac action potential propagation

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Rengasayee Veeraraghavan ◽  
Gregory S Hoeker ◽  
Anita Alvarez-Laviada ◽  
Daniel Hoagland ◽  
Xiaoping Wan ◽  
...  
Keyword(s):  
Action Potential ◽  
Sodium Current ◽  
Super Resolution ◽  
Cardiac Conduction ◽  
Impedance Sensing ◽  
Action Potential Propagation ◽  
Cell Substrate ◽  
Resolution Imaging ◽  
Novel Target ◽  
Ephaptic Coupling

Computational modeling indicates that cardiac conduction may involve ephaptic coupling – intercellular communication involving electrochemical signaling across narrow extracellular clefts between cardiomyocytes. We hypothesized that β1(SCN1B) –mediated adhesion scaffolds trans-activating NaV1.5 (SCN5A) channels within narrow (<30 nm) perinexal clefts adjacent to gap junctions (GJs), facilitating ephaptic coupling. Super-resolution imaging indicated preferential β1 localization at the perinexus, where it co-locates with NaV1.5. Smart patch clamp (SPC) indicated greater sodium current density (INa) at perinexi, relative to non-junctional sites. A novel, rationally designed peptide, βadp1, potently and selectively inhibited β1-mediated adhesion, in electric cell-substrate impedance sensing studies. βadp1 significantly widened perinexi in guinea pig ventricles, and selectively reduced perinexal INa, but not whole cell INa, in myocyte monolayers. In optical mapping studies, βadp1 precipitated arrhythmogenic conduction slowing. In summary, β1-mediated adhesion at the perinexus facilitates action potential propagation between cardiomyocytes, and may represent a novel target for anti-arrhythmic therapies.

scholarly journals Protection of Cardiac Cell-to-Cell Coupling Attenuate Myocardial Remodeling and Proarrhythmia Induced by Hypertension

2016 ◽  
pp. S29-S42 ◽  
Author(s):  
T. EGAN BENOVA ◽  
B. SZEIFFOVA BACOVA ◽  
C. VICZENCZOVA ◽  
E. DIEZ ◽  
M. BARANCIK ◽  
...  
Keyword(s):  
Heart Failure ◽  
Connexin 43 ◽  
Heart Function ◽  
Cardiac Conduction ◽  
Myocardial Remodeling ◽  
Omega 3 ◽  
Cell Coupling ◽  
Arrhythmic Death ◽  
Life Threatening ◽  
Antiarrhythmic Effects

Gap junction connexin channels are important determinants of myocardial conduction and synchronization that is crucial for coordinated heart function. One of the main risk factors for cardiovascular events that results in heart attack, congestive heart failure, stroke as well as sudden arrhythmic death is hypertension. Mislocalization and/or dysfunction of specific connexin-43 channels due to hypertension-induced myocardial remodeling have been implicated in the occurrence of life-threatening arrhythmias and heart failure in both, humans as well as experimental animals. Recent studies suggest that down-regulation of myocardial connexin-43, its abnormal distribution and/or phosphorylation might be implicated in this process. On the other hand, treatment of hypertensive animals with cardioprotective drugs (e.g. statins) or supplementation with non-pharmacological compounds, such as melatonin, omega-3 fatty acids and red palm oil protects from lethal arrhythmias. The antiarrhythmic effects are attributed to the attenuation of myocardial connexin-43 abnormalities associated with preservation of myocardial architecture and improvement of cardiac conduction. Findings uncover novel mechanisms of cardioprotective (antihypertensive and antiarrhythmic) effects of compounds that are used in clinical settings. Well-designed trials are needed to explore the antiarrhythmic potential of these compounds in patients suffering from hypertension.

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