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.

Cyamemazine metabolites: effects on human cardiac ion channels in-vitro and on the QTc interval in guinea pigs

2008 ◽  
Vol 60 (11) ◽  
pp. 1507-1513 ◽  
Author(s):  
William Crumb ◽  
Amine Benyamina ◽  
Christophe Arbus ◽  
George P. Thomas ◽  
Ricardo P. Garay ◽  
...  
Keyword(s):  
Ion Channels ◽  
Guinea Pigs ◽  
Qtc Interval ◽  
Cardiac Ion Channels

Abstract MP110: Inhibition of the Unfolded Protein Response Reduces Arrhythmic Risk After Myocardial Infarction

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Man Liu ◽  
Hong Liu ◽  
Preethy Parthiban ◽  
guangbin shi ◽  
Gyeoung-Jin Kang ◽  
...  
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
Ion Channel ◽  
Unfolded Protein Response ◽  
Coronary Artery Ligation ◽  
Unfolded Protein ◽  
Cardiac Ion Channels ◽  
Increased Risk ◽  
The Unfolded Protein Response ◽  
Protein Response

Background: Ischemic cardiomyopathy is associated with an increased risk of sudden death, activation of the unfolded protein response (UPR), and reductions in multiple cardiac ion channels and transporters. When activated, the protein kinase-like ER kinase (PERK) arm of the unfolded protein response (UPR) reduces protein translation and abundance. We hypothesize that inhibition of PERK could prevent cardiac ion channel downregulation and reduce arrhythmic risk after myocardial infarct (MI). Methods: The MI mouse model was induced by a left anterior descending coronary artery ligation. Pharmacological inhibition of PERK was achieved with a specific inhibitor, GSK2606414. Genetic inhibition of PERK was achieved by cardiac-specific PERK knockout in C57BL/6J mice (PERKKO). Echocardiography, telemetry, and electrophysiological measurements were performed to monitor cardiac function and arrhythmias. Results: Three weeks after surgery, the wild type MI mice exhibited decreased ejection fraction (EF%), ventricular tachycardia (VT) and prolonged QTc intervals. The UPR effectors (phospho-PERK, phospho-IRE1, and ATF6N) were elevated significantly (1.7- to 5.9-fold) at protein levels, and all major cardiac ion channels showed decreased protein expression in MI hearts. MI cardiomyocytes showed decreased currents for all major channels (I Na , I CaL , I to , I K1 , and I Kur : 60±6%, 53±9%, 27±6%, 55±7%, and 40±7% of sham, respectively, P<0.05 vs. sham) with significantly prolonged action potential duration (APD 90 : 291±43 ms of MI vs. 100±12 ms of sham, P<0.05) and decreased maximum upstroke velocity (dV/dt max : 95±4 V/s of MI vs. 132±6 ms of sham, P<0.05) of the action potential phase 0. GSK treatment restored I Na and I to , shortened APD, and increased dV/dt max . PERKKO mice exhibited reduced electrical remodeling in response to MI with shortened QTc intervals, less VT episodes, and higher survival rates. Conclusion: PERK is activated during MI and contributes to arrhythmic risk by downregulation of select cardiac ion channels. PERK inhibition prevented these changes and reduced arrhythmic risk. These results suggest that ion channel downregulation during MI is a fundamental arrhythmic mechanism and maintaining ion channel levels is antiarrhythmic.

scholarly journals Tox-Database.net: a curated resource for data describing chemical triggered in vitro cardiac ion channels inhibition

2012 ◽  
Vol 13 (1) ◽  
Author(s):  
Sebastian Polak ◽  
Barbara Wiśniowska ◽  
Anna Glinka ◽  
Miłosz Polak
Keyword(s):  
Ion Channels ◽  
Cardiac Ion Channels

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 Computational prediction of drug response in short QT syndrome type 1 based on measurements of compound effect in stem cell-derived cardiomyocytes

2021 ◽  
Vol 17 (2) ◽  
pp. e1008089
Author(s):  
Karoline Horgmo Jæger ◽  
Samuel Wall ◽  
Aslak Tveito
Keyword(s):  
Qt Interval ◽  
Drug Effects ◽  
Computational Prediction ◽  
Computational Procedure ◽  
Cardiac Cells ◽  
Qt Intervals ◽  
Increased Risk ◽  
Induced Pluripotent

Short QT (SQT) syndrome is a genetic cardiac disorder characterized by an abbreviated QT interval of the patient’s electrocardiogram. The syndrome is associated with increased risk of arrhythmia and sudden cardiac death and can arise from a number of ion channel mutations. Cardiomyocytes derived from induced pluripotent stem cells generated from SQT patients (SQT hiPSC-CMs) provide promising platforms for testing pharmacological treatments directly in human cardiac cells exhibiting mutations specific for the syndrome. However, a difficulty is posed by the relative immaturity of hiPSC-CMs, with the possibility that drug effects observed in SQT hiPSC-CMs could be very different from the corresponding drug effect in vivo. In this paper, we apply a multistep computational procedure for translating measured drug effects from these cells to human QT response. This process first detects drug effects on individual ion channels based on measurements of SQT hiPSC-CMs and then uses these results to estimate the drug effects on ventricular action potentials and QT intervals of adult SQT patients. We find that the procedure is able to identify IC50 values in line with measured values for the four drugs quinidine, ivabradine, ajmaline and mexiletine. In addition, the predicted effect of quinidine on the adult QT interval is in good agreement with measured effects of quinidine for adult patients. Consequently, the computational procedure appears to be a useful tool for helping predicting adult drug responses from pure in vitro measurements of patient derived cell lines.

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.

scholarly journals The Grapefruit Flavonoid Naringenin Inhibits Multiple Cardiac Ion Channels

2022 ◽  
Author(s):  
Camille Sanson ◽  
Rachid Boukaiba ◽  
Sylvie Houtmann ◽  
Magali-Anne Maizières ◽  
Sophie Fouconnier ◽  
...  
Keyword(s):  
Ion Channels ◽  
Grapefruit Juice ◽  
Rank Order ◽  
Cardiac Ion Channels ◽  
Mammalian Cell Lines ◽  
Significant Prolongation ◽  
Citrus Juices ◽  
Automated Patch Clamp ◽  
Electrocardiogram Ecg

Abstract Drinking fresh grapefruit juice is associated with a significant prolongation of the QT segment on the electrocardiogram (ECG) in healthy volunteers. Among the prominent flavonoids contained in citrus fruits, the flavanone naringenin is known to be a blocker of the human ether-a-go-go related gene (hERG) potassium channel. We hypothesized that naringenin could interfere with other major ion channels shaping the cardiac ventricular action potential (AP). To this end, we examined the effects of naringenin on the seven currents comprising the Comprehensive in vitro Pro-Arrhythmia (CiPA) panel for early arrhythmogenic risk assessment in drug discovery and development. We used automated patch-clamp of human ion channels heterologously expressed in mammalian cell lines to evaluate half-maximal inhibitory concentrations (IC50). Naringenin blocked all CiPA currents tested with IC50 values in the 30 µM – 100 µM concentration-range. The rank-order of channel sensitivity was the following: hERG > Kir2.1 > NaV1.5 late > NaV1.5 peak > KV7.1 > KV4.3 > CaV1.2. This multichannel inhibitory profile of naringenin suggests exercising caution when large amounts of grapefruit juice or other citrus juices enriched in this flavanone are drunk in conjunction with QT prolonging drugs or by carriers of congenital long QT syndromes.

Cyamemazine metabolites: effects on human cardiac ion channels in-vitro and on the QTc interval in guinea pigs

2008 ◽  
Vol 60 (11) ◽  
pp. 1507-1513
Author(s):  
William Crumb ◽  
Amine Benyamina ◽  
Christophe Arbus ◽  
George P. Thomas ◽  
Ricardo P. Garay ◽  
...  
Keyword(s):  
Ion Channels ◽  
Guinea Pigs ◽  
Qtc Interval ◽  
Cardiac Ion Channels

In-vitro Comparative study on blood clotting time of some Plants Extracts and Heparin when Infected with Snakebite

2021 ◽  
pp. 2915-2918
Author(s):  
Khalid Abdulkareem Mohammad
Keyword(s):  
Comparative Study ◽  
Blood Clotting ◽  
Nigella Sativa ◽  
Still Life ◽  
Medicinal Use ◽  
Snake Bites ◽  
Life Threatening ◽  
The Common ◽  
Bite Injuries

Around the world, snake bite injuries are still life threatening and require intensive care. The diagnose and treatment to toxic snake bites is the insufficient information, within the management of anti-toxin therapy, is not provided in clinical practice. In this comparative study, water extracts of Allium sativum, Allium cepa and Nigella sativa in different concentrations and heparin powder was used on human blood which is free from diseases. The common desert snake poison was used to compare the anti-coagulation time of the above plant extracts. Among three extracts Nigella sativa extract showed more time of coagulation of blood when treated with the snake poison. The results of the present study confirms the traditional medicinal use of selected plants and evidence for the best substances impact in the delay of blood clotting against snake bites of those plants. Further research is going on to isolate bioactive compounds.

Sign in / Sign up

Export Citation Format

Share Document