scholarly journals Rutaecarpine targets hERG channels and participates in regulating electrophysiological properties leading to ventricular arrhythmia

2021 ◽  
Author(s):  
Ge Zhan ◽  
Fang Wang ◽  
Yun‐qi Ding ◽  
Xiang‐hua Li ◽  
Yue‐xin Li ◽  
...  
Keyword(s):  
Ventricular Arrhythmia ◽  
Electrophysiological Properties ◽  
Herg Channels

Abstract 2736: Mutations In The Nonpore Region of The HERG Gene Are at Risk of Acquired Long QT Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Yuichiro Sakamoto ◽  
Hidekazu Ino ◽  
Noboru Fujino ◽  
Katsuharu Uchiyama ◽  
Kenshi Hayashi ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Electrophysiological Study ◽  
Herg Channel ◽  
Cardiac Events ◽  
Electrophysiological Properties ◽  
Acquired Long Qt Syndrome ◽  
Increased Risk ◽  
Increase Risk ◽  
Few Data ◽  
Herg Channels

Introduction : Mutations involving the KCNH2 gene in HERG channel are responsible for type2 LQTS. Previous study showed patients with mutations in the pore region of the HERG gene are markedly increased risk for arrhythmia-related cardiac events compared with patients with nonpore mutations. However, a few data exist regarding mode of onset and frequency in arrhythmic events of mutations in the nonpore regions of the HERG channel. Hypothesis :We hypothesized that patients with mutations in the nonpore regions of the HERG gene increase risk for cardiac events under a specific condition. Methods: We examined 104 unrelated subjects with LQTS. Genetic analysis of KCNH2 gene was performed using standard genetic tests for probands and families of genotyped ones.Between subjects with and without pore mutations,difference in clinical characteristics such as QTc intervals, LQT score and major cardiac events are evaluated by standard statistical methods. Result: We identified 7 LQT2 patients with 3 pore mutations and 17 patients with 7 nonpore mutation, and evaluated clinical characteristics and characterized the electrophysiological properties of these mutations. The baseline QTc intervals were significantly longer with pore than with nonpore mutations (513 ± 60ms vs. 479 ± 21ms, p<0.01). The LQTS scores determined by Schwartz’s criteria were also significantly higher with pore mutations (4.5 ± 1.2 vs. 2.9 ± 1.2, p<0.01). However the frequency of LQTS-related cardiac events with nonpore mutaion was as high as with pore mutations (57 % vs. 30 %, N.S). Significantly 4 of 5 cardiac events with nonpore mutations occurred under medications (Probucol) or conditions (Hypokalemia) known to favor QT prolongation, although only 1 of 4 cardiac events with pore mutations did. Electrophysiological study revealed that the tail current amplitude through one nonpore mutant channel(M124T)was significantly decreased as compared that of WT HERG channel and Probucol significantly inhibited M124T HERG channels. Conclusions: These data demonstrate that LQT2 patients with nonpore mutations are also at high risk of arrhythmia-related events in the presence of drugs or other environmental stressors.

The EGFP/hERG fusion protein alter the electrophysiological properties of hERG channels in HEK293 cells

2011 ◽  
Vol 35 (3) ◽  
pp. 193-199 ◽  
Author(s):  
Na Huang ◽  
Jiang‑Fang Lian ◽  
Jian‑Hua Huo ◽  
Li‑Ying Liu ◽  
Lei Ni ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Hek293 Cells ◽  
Electrophysiological Properties ◽  
Herg Channels

scholarly journals Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility

2021 ◽  
Vol 8 ◽  
Author(s):  
Yung-Nan Tsai ◽  
Ya-Wen Hsiao ◽  
Shien-Fong Lin ◽  
Yi-Hsin Chan ◽  
Yu-Cheng Hsieh ◽  
...  
Keyword(s):  
Ventricular Arrhythmia ◽  
Intracellular Calcium ◽  
Polymerase Chain Reaction Analysis ◽  
Dominant Frequency ◽  
Calcium Handling ◽  
Interleukin 17 ◽  
Release Channel ◽  
Maximum Slope ◽  
Electrophysiological Properties ◽  
Phase Singularities

Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Cai) handling and VA susceptibility by IL-17.Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Cai transient duration (CaiTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed.Results: There were longer APD80, CaiTD80 and increased thresholds of APD and CaiTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor Ca2+ release channel were upregulated, and the subunit of L-type Ca2+ current and sarcoplasmic reticulum Ca2+-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group.Conclusions: IL-17 enhanced CaiTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.

Redox State in Atrial Fibrillation Pathogenesis and Relevant Therapeutic Approaches

2019 ◽  
Vol 26 (5) ◽  
pp. 765-779 ◽  
Author(s):  
Alexios S. Antonopoulos ◽  
Athina Goliopoulou ◽  
Evangelos Oikonomou ◽  
Sotiris Tsalamandris ◽  
Georgios-Angelos Papamikroulis ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Studies ◽  
Redox State ◽  
Redox Balance ◽  
Therapeutic Approaches ◽  
Critical Determinant ◽  
Electrophysiological Properties ◽  
Antioxidant Agents ◽  
Clinical Benefits

Background: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. Objective: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. Method: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. Results: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). Conclusion: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.

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