BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
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2017
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IF 3.498
Chunxia Yin,Yaoxu Chen,Huanlin Wu,Danping Xu,Wen Tan
Isosteviol has been demonstrated to play a protective role during ischemia reperfusion (I/R) myocardial infarction. However, the underlying electrophysiological mechanisms of isosteviol are still unknown. Our previous study showed that the rapid component of the delayed rectifier potassium channel (I Kr ) plays an important role in the prolongation of I/R-induced QT interval-related arrhythmia. This study aimed to investigate whether isosteviol could attenuate I/R-induced prolongation of the action potential duration (APD) along with inhibition of I Kr , and we aimed to clarify the electrophysiological mechanism of isosteviol to determine its cardioprotective effects in guinea pigs. We observed that the APD 90 were 298.5 ± 41.6 ms in control, 528.6 ± 56.7 ms during I/R, and reduced to 327.8 ± 40.5 ms after 10 μmol/L of isosteviol treatment. The I Kr currents were 1.44 ± 0.06 pA·pF − 1 in the control group, 0.50 ± 0.07 pA·pF − 1 during I/R, and recovered to 1.20 ± 0.12 pA·pF − 1 after 10 μmol/L of isoteviol treatment. Moreover, isosteviol reduced the over-production of reactive oxygen species (ROS) during I/R. Importantly, isosteviol does not affect the I Kr and human ether-a-go-go-related gene currents of normal cardiomyocytes. It attenuated the I/R-induced inhibition of I Kr due to reduced over-production of ROS. Furthermore, isosteviol is safe and has no cardiotoxicity, and it might be beneficial for coronary reperfusion therapy.
研究领域:
药理学
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心脏电生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
·
2017
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IF 3.498
Zhuo Fan,Nanying Lv,Xiao Luo,Wen Tan
Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of I to is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for I to and I CaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of I to and I CaL are correlated to the alterations of the mRNA transcription level.
研究领域:
药理学
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心血管病学
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DOI
PubMed
高影响因子
PLoS One
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2013
·Vol. 8
·期 8
·e70565
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IF 3.73
Luyan Guo,Yanyan Xing,Rui Pan,Mingliang Jiang,Zheng Gong,Liqing Lin,Junbing Wang,Guoyin Xiong,Jun Dong
Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9) and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop) protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K + ) current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K + channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K + channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K + current.
研究领域:
神经科学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neuroscience Bulletin
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2025
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IF 5.8
Wang Jinyu,Xu Mengfan,Zhang Lei,Liu Wenjie,Wang Siyue,Wang Liqin,Cong Ning,Li Geng-Lin,Wang Jing
Vestibular efferent neurons in the brainstem provide direct cholinergic innervation to peripheral vestibular organs, thereby modulating their sensory responsiveness. In this study, a genetically targeted mouse model with choline acetyltransferase-driven fluorescent labeling enabled the precise localization of these neurons to the dorsolateral region of the genu of the facial nerve. Whole-cell patch-clamp recordings in acute brainstem slices revealed that virtually all neurons exhibited spontaneous action potential firing, with marked heterogeneity in discharge patterns and after-hyperpolarization kinetics. Prominent A-type potassium currents were identified and found to be differentially regulated by acetylcholine and calcitonin gene-related peptide. Acute unilateral vestibular deprivation induced a bilateral enhancement of spontaneous firing, indicating sensitivity to altered sensory input. These findings define the intrinsic electrophysiological properties and neuromodulatory mechanisms of vestibular efferent neurons, providing mechanistic insight into their roles in both physiological regulation and adaptive plasticity within the vestibular system.
研究领域:
神经科学
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电生理学
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前庭系统
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神经可塑性
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感觉处理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
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2020
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IF 3.647
Xiuhuan Chen,Cui Zhang,Yan Guo,Xin Liu,Tianxin Ye,Yuhong Fo,Chuan Qu,Jinjun Liang,Shaobo Shi,Bo Yang
Aim The purpose of the study was to investigate what effects the sigma-1 receptor (S1R) could exert on the cardiac myocyte ion channels in a rodent model of depression and to explore the underlying mechanisms since depression is an independent risk factor for cardiovascular diseases including ventricular arrhythmias (VAs). Materials and methods To establish the depression model in rats, chronic mild unpredictable stress (CMUS) for 28 days was used. The S1R agonist fluvoxamine was injected intraperitoneally from the second week to the last week for 21 days in total, and the effects were evaluated by patch clamp, western blot analysis, and Masson staining. Key findings We demonstrated that depression was improved after treatment with fluvoxamine. In addition, the prolongation of the corrected QT (QTc) interval under CMUS that increased vulnerability to VAs was significantly attenuated by stimulation of S1R due to the decreased amplitude of L-type calcium current (I Ca-L ) and the restoration of reduced transient outward potassium current (I to ) resulting from CMUS induction. The S1R also decelerated I to inactivation and accelerated I to recovery by activating Ca 2+ /calmodulin-dependent kinase II. Moreover, the stimulation of S1R ameliorated the structural remodeling as the substrate for maintenance of VAs. All these effects were abolished by the administration of S1R antagonist BD1047, which verified the roles for S1R. Significance Activation of S1R could decrease the vulnerability to VAs by inhibiting I Ca-L and restoring I to , in addition to ameliorating the CMUS-induced depressive symptoms and structural remodeling.
研究领域:
药理学
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心脏病学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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