scholarly journals Functional suppression of Kcnq1 leads to early sodium channel remodelling and cardiac conduction system dysmorphogenesis

2013 ◽  
Vol 98 (3) ◽  
pp. 504-514 ◽  
Author(s):  
Angel J. de la Rosa ◽  
Jorge N. Domínguez ◽  
David Sedmera ◽  
Bara Sankova ◽  
Leif Hove-Madsen ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System

Sodium channel kinetic changes that produce Brugada syndrome or progressive cardiac conduction system disease

2007 ◽  
Vol 292 (1) ◽  
pp. H399-H407 ◽  
Author(s):  
Zhu-Shan Zhang ◽  
Joseph Tranquillo ◽  
Valentina Neplioueva ◽  
Nenad Bursac ◽  
Augustus O. Grant
Keyword(s):  
Action Potential ◽  
Sodium Channel ◽  
Brugada Syndrome ◽  
Sodium Current ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Wild Type ◽  
System Disease ◽  
Conduction System Disease

Some mutations of the sodium channel gene NaV1.5 are multifunctional, causing combinations of LQTS, Brugada syndrome and progressive cardiac conduction system disease (PCCD). The combination of Brugada syndrome and PCCD is uncommon, although they both result from a reduction in the sodium current. We hypothesize that slow conduction is sufficient to cause S-T segment elevation and undertook a combined experimental and theoretical study to determine whether conduction slowing alone can produce the Brugada phenotype. Deletion of lysine 1479 in one of two positively charged clusters in the III/IV inter-domain linker causes both syndromes. We have examined the functional effects of this mutation using heterologous expression of the wild-type and mutant sodium channel in HEK-293-EBNA cells. We show that ΔK1479 shifts the potential of half-activation, V1/2m, to more positive potentials ( V1/2m = −36.8 ± 0.8 and −24.5 ± 1.3 mV for the wild-type and ΔK1479 mutant respectively, n = 11, 10). The depolarizing shift increases the extent of depolarization required for activation. The potential of half-inactivation, V1/2h, is also shifted to more positive potentials ( V1/2h = −85 ± 1.1 and −79.4 ± 1.2 mV for wild-type and ΔK1479 mutant respectively), increasing the fraction of channels available for activation. These shifts are quantitatively the same as a mutation that produces PCCD only, G514C. We incorporated experimentally derived parameters into a model of the cardiac action potential and its propagation in a one dimensional cable (simulating endo-, mid-myocardial and epicardial regions). The simulations show that action potential and ECG changes consistent with Brugada syndrome may result from conduction slowing alone; marked repolarization heterogeneity is not required. The findings also suggest how Brugada syndrome and PCCD which both result from loss of sodium channel function are sometimes present alone and at other times in combination.

scholarly journals Sudden Unexpected Death Associated with Arrhythmogenic Cardiomyopathy: Study of the Cardiac Conduction System

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1323
Author(s):  
Giulia Ottaviani ◽  
Graziella Alfonsi ◽  
Simone G. Ramos ◽  
L. Maximilian Buja
Keyword(s):  
Fibromuscular Dysplasia ◽  
Ventricular Myocardium ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Future Research ◽  
Cardiac Conduction System ◽  
Arrhythmogenic Cardiomyopathy ◽  
Unexpected Death ◽  
The Past ◽  
The Right

A retrospective study was conducted on pathologically diagnosed arrhythmogenic cardiomyopathy (ACM) from consecutive cases over the past 34 years (n = 1109). The anatomo-pathological analyses were performed on 23 hearts diagnosed as ACM (2.07%) from a series of 1109 suspected cases, while histopathological data of cardiac conduction system (CCS) were available for 15 out of 23 cases. The CCS was removed in two blocks, containing the following structures: Sino-atrial node (SAN), atrio-ventricular junction (AVJ) including the atrio-ventricular node (AVN), the His bundle (HB), the bifurcation (BIF), the left bundle branch (LBB) and the right bundle branch (RBB). The ACM cases consisted of 20 (86.96%) sudden unexpected cardiac death (SUCD) and 3 (13.04%) native explanted hearts; 16 (69.56%) were males and 7 (30.44%) were females, ranging in age from 5 to 65 (mean age ± SD, 36.13 ± 16.06) years. The following anomalies of the CCS, displayed as percentages of the 15 ACM SUCD cases in which the CCS has been fully analyzed, have been detected: Hypoplasia of SAN (80%) and/or AVJ (86.67%) due to fatty-fibrous involvement, AVJ dispersion and/or septation (46.67%), central fibrous body (CFB) hypoplasia (33.33%), fibromuscular dysplasia of SAN (20%) and/or AVN (26.67%) arteries, hemorrhage and infarct-like lesions of CCS (13.33%), islands of conduction tissue in CFB (13.33%), Mahaim fibers (13.33%), LBB block by fibrosis (13.33%), AVN tongue (13.33%), HB duplicity (6.67%%), CFB cartilaginous meta-hyperplasia (6.67%), and right sided HB (6.67%). Arrhythmias are the hallmark of ACM, not only from the fatty-fibrous disruption of the ventricular myocardium that accounts for reentrant ventricular tachycardia, but also from the fatty-fibrous involvement of CCS itself. Future research should focus on application of these knowledge on CCS anomalies to be added to diagnostic criteria or at least to be useful to detect the patients with higher sudden death risks.

Sudden death due to lymphomatous infiltration of the cardiac conduction system

2003 ◽  
Vol 12 (2) ◽  
pp. 77-81 ◽  
Author(s):  
Giulia Ottaviani ◽  
Luigi Matturri ◽  
Lino Rossi ◽  
Dan Jones
Keyword(s):  
Sudden Death ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System

scholarly journals Regulation of Cardiac Conduction and Arrhythmias by Ankyrin/Spectrin-Based Macromolecular Complexes

2021 ◽  
Vol 8 (5) ◽  
pp. 48
Author(s):  
Drew Nassal ◽  
Jane Yu ◽  
Dennison Min ◽  
Cemantha Lane ◽  
Rebecca Shaheen ◽  
...  
Keyword(s):  
Ion Channels ◽  
Cardiac Disease ◽  
Conduction System ◽  
Cytoskeletal Proteins ◽  
Cardiac Conduction ◽  
Proper Function ◽  
Cardiac Conduction System ◽  
Loss Of Function ◽  
Macromolecular Complexes ◽  
Conduction Disturbances

The cardiac conduction system is an extended network of excitable tissue tasked with generation and propagation of electrical impulses to signal coordinated contraction of the heart. The fidelity of this system depends on the proper spatio-temporal regulation of ion channels in myocytes throughout the conduction system. Importantly, inherited or acquired defects in a wide class of ion channels has been linked to dysfunction at various stages of the conduction system resulting in life-threatening cardiac arrhythmia. There is growing appreciation of the role that adapter and cytoskeletal proteins play in organizing ion channel macromolecular complexes critical for proper function of the cardiac conduction system. In particular, members of the ankyrin and spectrin families have emerged as important nodes for normal expression and regulation of ion channels in myocytes throughout the conduction system. Human variants impacting ankyrin/spectrin function give rise to a broad constellation of cardiac arrhythmias. Furthermore, chronic neurohumoral and biomechanical stress promotes ankyrin/spectrin loss of function that likely contributes to conduction disturbances in the setting of acquired cardiac disease. Collectively, this review seeks to bring attention to the significance of these cytoskeletal players and emphasize the potential therapeutic role they represent in a myriad of cardiac disease states.

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