scholarly journals Mechanisms and Alterations of Cardiac Ion Channels Leading to Disease: Role of Ankyrin-B in Cardiac Function

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 211 ◽  
Author(s):  
Holly C. Sucharski ◽  
Emma K. Dudley ◽  
Caullin B.R. Keith ◽  
Mona El Refaey ◽  
Sara N. Koenig ◽  
...  
Keyword(s):  
Ion Channels ◽  
Cardiac Function ◽  
Cell Biology ◽  
Sinus Node ◽  
Conduction Block ◽  
Cardiac Ion Channels ◽  
Life Threatening ◽  
Ankyrin B ◽  
Normal Cardiac Function

Ankyrin-B (encoded by ANK2), originally identified as a key cytoskeletal-associated protein in the brain, is highly expressed in the heart and plays critical roles in cardiac physiology and cell biology. In the heart, ankyrin-B plays key roles in the targeting and localization of key ion channels and transporters, structural proteins, and signaling molecules. The role of ankyrin-B in normal cardiac function is illustrated in animal models lacking ankyrin-B expression, which display significant electrical and structural phenotypes and life-threatening arrhythmias. Further, ankyrin-B dysfunction has been associated with cardiac phenotypes in humans (now referred to as “ankyrin-B syndrome”) including sinus node dysfunction, heart rate variability, atrial fibrillation, conduction block, arrhythmogenic cardiomyopathy, structural remodeling, and sudden cardiac death. Here, we review the diverse roles of ankyrin-B in the vertebrate heart with a significant focus on ankyrin-B-linked cell- and molecular-pathways and disease.

Discordant S-T alternans contributes to formation of reentry: a possible mechanism of reperfusion arrhythmia

1998 ◽  
Vol 275 (1) ◽  
pp. H116-H121 ◽  
Author(s):  
Hidetada Tachibana ◽  
Isao Kubota ◽  
Michiyasu Yamaki ◽  
Tetsu Watanabe ◽  
Hitonobu Tomoike
Keyword(s):  
Coronary Artery ◽  
Ventricular Fibrillation ◽  
Conduction Block ◽  
Activation Time ◽  
Reperfusion Arrhythmia ◽  
Open Chest ◽  
Life Threatening ◽  
Control State ◽  
Reentrant Circuit

Although a relationship between S-T alternans and life-threatening arrhythmia has been recognized, the mechanism is poorly understood. We examine the role of S-T alternans in the occurrence of ventricular fibrillation (VF) after reperfusion. The left anterior descending coronary artery was occluded for 20 min and then abruptly reperfused in 12 intravenously anesthetized open-chest dogs. Sixty unipolar epicardial electrograms were recorded during the control state, at the end of occlusion, and after reperfusion. The largest magnitude of S-T alternans among 60 leads was defined as the maximum S-T alternans. Isochronal maps of activation time in paced beat and spontaneous ventricular premature contractions (VPC) were analyzed. After reperfusion, VF ensued in six dogs. The maximum S-T alternans augmented progressively with time after reperfusion until VF occurred. In three dogs with VF, when activation of VPC resulted in conduction block and formed reentry, VF ensued. The conduction block was located between sites of discordant S-T alternans (S-T alternans at adjacent leads was out of phase). These data indicate that discordant S-T alternans relates to VF by facilitating the formation of a reentrant circuit.

Abstract 62: The Coxsackie Virus B3 modulates Cardiac Ion Channels

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Guiscard Seebohm ◽  
Katja Steinke ◽  
Ulrike Henrion ◽  
Nicole Ettischer ◽  
Frank Sachse ◽  
...  
Keyword(s):  
Ion Channels ◽  
Cardiac Cells ◽  
Coxsackie Virus ◽  
Cardiac Ion Channels ◽  
Increased Risk ◽  
Chronic Myocarditis ◽  
Life Threatening ◽  
The Common ◽  
In Silico Analyses

Infections with coxsackieviruses of type B (CVB) induce severe forms of acute and chronic myocarditis that are often accompanied by ventricular arrhythmias. The mechanisms underlying the development of virus-induced, life-threatening arrhythmia, remain largely elusive. Here, we show time-dependent CVB3-induced modulation of the cardiac ion channels Kv7.1, hERG1 and CaV1.2 in vitro. Channel protein localizations within cells and plasma membrane abundance are altered in infected mouse cardiac cells. In silico analyses of infected human myocytes suggest increased risk of arrhythmogenesis. These modifications are attenuated by the common Asian polymorphism KCNQ1-P448R, a genetic determinant preventing coxsackievirus-induced effects in vitro. This study provides a previously unknown explanation for the development of arrhythmias in enteroviral myocarditis, which will help to develop therapeutic strategies for arrhythmia treatment.

scholarly journals Hyperkalemia Induced Brugada Phenocopy: A Rare ECG Manifestation

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Muhammad Ameen ◽  
Ghulam Akbar ◽  
Naeem Abbas ◽  
Ghazi Mirrani
Keyword(s):  
Ion Channels ◽  
Ventricular Arrhythmias ◽  
Cardiac Conduction ◽  
St Segment Elevation ◽  
Electrolyte Disturbances ◽  
Cardiac Ion Channels ◽  
St Segment ◽  
Life Threatening ◽  
Severe Hyperkalemia ◽  
Brugada Pattern

Brugada syndrome (BrS) is an inherited disorder of cardiac ion channels characterized by peculiar ECG findings predisposing individuals to ventricular arrhythmias, syncope, and sudden cardiac death (SCD). Various electrolyte disturbances and ion channels blocking drugs could also provoke BrS ECG findings without genetic BrS. Clinical differentiation and recognition are essential for guiding the legitimate action. Hyperkalemia is well known to cause a wide variety of ECG manifestations. Severe hyperkalemia can even cause life threatening ventricular arrhythmias and cardiac conduction abnormalities. Most common ECG findings include peaked tall T waves with short PR interval and wide QRS complex. Since it is very commonly encountered disorder, physicians need to be aware of even its rare ECG manifestations, which include ST segment elevation and Brugada pattern ECG (BrP). We are adding a case to the limited literature about hyperkalemia induced reversible Brugada pattern ECG changes.

scholarly journals PRMT7 Ablation in Cardiomyocytes Causes Cardiac Hypertrophy and Fibrosis Through β-Catenin Dysregulation

2021 ◽  
Author(s):  
Byeong-Yun Ahn ◽  
Myong-Ho Jeong ◽  
Jung-Hoon Pyun ◽  
Hyeon-Ju Jeong ◽  
Tuan Anh Vuong ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Wnt Signaling Pathway ◽  
Rat Cardiomyocytes ◽  
Hypertrophic Response ◽  
Cellular Hypertrophy ◽  
Pathway Inhibition ◽  
Normal Cardiac Function ◽  
Inhibitor Treatment

Abstract Angiotensin II (AngII) has potent cardiac hypertrophic effects mediated through activation of hypertrophic signaling like Wnt/b-Catenin signaling. In the current study, we examined the role of protein arginine methyltransferase 7 (PRMT7) in cardiac function. PRMT7 was greatly decreased in hypertrophic hearts chronically infused with AngII and cardiomyocytes treated with AngII. PRMT7 depletion in rat cardiomyocytes resulted in hypertrophic responses. Consistently, mice lacking PRMT7 exhibited displayed the cardiac hypertrophy and fibrosis. PRMT7 overexpression abrogated the cellular hypertrophy elicited by AngII, while PRMT7 depletion exacerbated the hypertrophic response caused by AngII. Similar with AngII treatment, the cardiac transcriptome analysis of PRMT7-deficient hearts revealed the alteration in gene expression profile related to Wnt signaling pathway. Inhibition of PRMT7 by gene deletion or an inhibitor treatment enhanced the activity of b-Catenin. PRMT7 deficiency decreases symmetric dimethylation of b-Catenin. Mechanistic studies reveal that methylation of arginine residue 93 in b-Catenin decreases the activity of b-Catenin. Taken together, our data suggest that PRMT7 is important for normal cardiac function through suppression of b-Catenin activity.

Basic Cardiac Electrophysiology

2013 ◽  
pp. 171-190
Author(s):  
Hon-Chi Lee ◽  
Arshad Jahangir
Keyword(s):  
Ion Channels ◽  
Cardiac Arrhythmias ◽  
Action Potentials ◽  
Cardiac Electrophysiology ◽  
Structure And Function ◽  
Learning Objectives ◽  
Cardiac Ion Channels ◽  
Cardiac Action ◽  
And Function

The learning objectives of this chapter are to review some basic electrophysiologic concepts that are useful for the clinician. These include 1) the structure and function of cardiac ion channels; 2) the role of ion channels in the generation of cardiac action potentials; 3) the mechanisms of cardiac arrhythmias; and 4) inherited and acquired channelopathies.

Role of Ion Channels and Transporters in Cell Migration

2012 ◽  
Vol 92 (4) ◽  
pp. 1865-1913 ◽  
Author(s):  
Albrecht Schwab ◽  
Anke Fabian ◽  
Peter J. Hanley ◽  
Christian Stock
Keyword(s):  
Cell Migration ◽  
Ion Channels ◽  
Immune Defense ◽  
The Body ◽  
Cellular Migration ◽  
Physiological Processes ◽  
Life Threatening ◽  
Health And Disease ◽  
Tumor Metastases

Cell motility is central to tissue homeostasis in health and disease, and there is hardly any cell in the body that is not motile at a given point in its life cycle. Important physiological processes intimately related to the ability of the respective cells to migrate include embryogenesis, immune defense, angiogenesis, and wound healing. On the other side, migration is associated with life-threatening pathologies such as tumor metastases and atherosclerosis. Research from the last ∼15 years revealed that ion channels and transporters are indispensable components of the cellular migration apparatus. After presenting general principles by which transport proteins affect cell migration, we will discuss systematically the role of channels and transporters involved in cell migration.

scholarly journals Computational biology in the study of cardiac ion channels and cell electrophysiology

2006 ◽  
Vol 39 (1) ◽  
pp. 57-116 ◽  
Author(s):  
Yoram Rudy ◽  
Jonathan R. Silva
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
Ion Channel ◽  
Markov Models ◽  
Cardiac Action Potential ◽  
Genetic Mutations ◽  
Cardiac Ion Channels ◽  
Cardiac Action ◽  
Ion Channel Kinetics

1. Prologue 582. The Hodgkin–Huxley formalism for computing the action potential 592.1 The axon action potential model 592.2 Cardiac action potential models 623. Ion-channel based formulation of the action potential 653.1 Ion-channel structure 653.2 Markov models of ion-channel kinetics 663.3 Role of selected ion channels in rate dependence of the cardiac action potential 713.4 Physiological implications of IKs subunit interaction 773.5 Mechanism of cardiac action potential rate-adaptation is species dependent 784. Simulating ion-channel mutations and their electrophysiological consequences 814.1 Mutations in SCN5A, the gene that encodes the cardiac sodium channel 824.1.1 The ΔKPQ mutation and LQT3 824.1.2 SCN5A mutation that underlies a dual phenotype 874.2 Mutations in HERG, the gene that encodes IKr: re-examination of the ‘gain of function/loss of function’ concept 944.3 Role of IKs as ‘repolarization reserve’ 1005. Modeling cell signaling in electrophysiology 1025.1 CaMKII regulation of the Ca2+ transient 1025.2 The β-adrenergic signaling cascade 1056. Epilogue 1077. Acknowledgments 1088. References 109The cardiac cell is a complex biological system where various processes interact to generate electrical excitation (the action potential, AP) and contraction. During AP generation, membrane ion channels interact nonlinearly with dynamically changing ionic concentrations and varying transmembrane voltage, and are subject to regulatory processes. In recent years, a large body of knowledge has accumulated on the molecular structure of cardiac ion channels, their function, and their modification by genetic mutations that are associated with cardiac arrhythmias and sudden death. However, ion channels are typically studied in isolation (in expression systems or isolated membrane patches), away from the physiological environment of the cell where they interact to generate the AP. A major challenge remains the integration of ion-channel properties into the functioning, complex and highly interactive cell system, with the objective to relate molecular-level processes and their modification by disease to whole-cell function and clinical phenotype. In this article we describe how computational biology can be used to achieve such integration. We explain how mathematical (Markov) models of ion-channel kinetics are incorporated into integrated models of cardiac cells to compute the AP. We provide examples of mathematical (computer) simulations of physiological and pathological phenomena, including AP adaptation to changes in heart rate, genetic mutations in SCN5A and HERG genes that are associated with fatal cardiac arrhythmias, and effects of the CaMKII regulatory pathway and β-adrenergic cascade on the cell electrophysiological function.

Role of kinins in chronic heart failure and in the therapeutic effect of ACE inhibitors in kininogen-deficient rats

2000 ◽  
Vol 278 (2) ◽  
pp. H507-H514 ◽  
Author(s):  
Yun-He Liu ◽  
Xiao-Ping Yang ◽  
Dharmesh Mehta ◽  
Manohar Bulagannawar ◽  
Gloria M. Scicli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Infarct Size ◽  
Receptor Antagonist ◽  
Cardiac Remodeling ◽  
Myocardial Infarct ◽  
Brown Norway ◽  
Myocardial Infarct Size ◽  
Normal Cardiac Function

Using Brown Norway Katholiek (BNK) rats, which are deficient in kininogen (kinin precursor) due to a mutation in the kininogen gene, we examined the role of endogenous kinins in 1) normal cardiac function; 2) myocardial infarction (MI) caused by coronary artery ligation; 3) cardiac remodeling in the development of heart failure (HF) after MI; and 4) the cardioprotective effect of angiotensin-converting enzyme inhibitors (ACEI) on HF after MI. Two months after MI, rats were randomly treated with vehicle or the ACEI ramipril for 2 mo. Brown Norway rats (BN), which have normal kininogen, were used as controls. Left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), end-diastolic pressure (EDP), and ejection fraction (EF) as well as myocardial infarct size (IS), interstitial collagen fraction (ICF), cardiomyocyte cross-sectional area (MCA), and oxygen diffusion distance (ODD) were measured. We found that 1) cardiac hemodynamics, function, and histology were the same in sham-ligated BN and BNK rats; 2) IS was similar in BN and BNK; 3) in rats with HF treated with vehicle, the decrease in LVEF and the increase in LVEDV, LVESV, LVEDP, ICF, MCA, and ODD did not differ between BNK and BN; and 4) ACEI increased EF, decreased LVEDV and LVESV, and improved cardiac remodeling in BN-HF rats, and these effects were partially blocked by the bradykinin B2 receptor antagonist icatibant (HOE-140). In BNK-HF rats, ACEI failed to produce these beneficial cardiac effects. We concluded that in rats, lack of kinins does not influence regulation of normal cardiac function, myocardial infarct size, or development of HF; however, kinins appear to play an important role in the cardioprotective effect of ACEI, since 1) this effect was significantly diminished in kininogen-deficient rats and 2) it was blocked by a B2 kinin receptor antagonist in BN rats.

scholarly journals MiR-486-3p and MiR-938—Important Inhibitors of Pacemaking Ion Channels and/or Markers of Immune Cells

2021 ◽  
Vol 11 (23) ◽  
pp. 11366
Author(s):  
Abimbola J Aminu ◽  
Maria Petkova ◽  
Weixuan Chen ◽  
Zeyuan Yin ◽  
Vlad S Kuzmin ◽  
...  
Keyword(s):  
Ion Channels ◽  
Mast Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Luciferase Activity ◽  
Sinus Node ◽  
Luciferase Assay ◽  
Potential Therapeutic Target ◽  
The Right

The sinus node (SN) is the heart’s primary pacemaker and has a unique expression of pacemaking ion channels and immune cell markers. The role of microribonucleic acids (miRNAs) in control of ion channels and immune function of the sinus node is not well understood. We have recently shown that hsa-miR-486-3p downregulates the main pacemaking channel HCN4 in the SN. In addition, we recently demonstrated that immune cells are significantly more abundant in the SN compared to the right atrium. The aim of this study was to validate the previously predicted interactions between miRNAs and mRNAs of key Ca2+ ion channels (involved in peacemaking) and mRNA of TPSAB1—(a mast cells marker) using luciferase assay. We now show that miR-486 significantly downregulates Cav1.3, Cav3.1, and TPSAB1-mediated luciferase activity, while miR-938 significantly downregulates only TPSAB1-mediated luciferase activity. This makes miR-486-3p a potential therapeutic target in the treatment of SN dysfunctions.

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