Cellular Basis for Autonomic Regulation of Cardiac Arrhythmias
心律失常自主调节的细胞基础
基本信息
- 批准号:10627578
- 负责人:
- 金额:$ 39.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-10 至 2028-07-31
- 项目状态:未结题
- 来源:
- 关键词:AcetylcholineAction PotentialsAdrenergic AgentsAffectAmericanAnatomyAnimal ModelAreaArrhythmiaBiochemicalCardiacCell SeparationCellsChronicComputer ModelsDataDependenceDiseaseElectrophysiology (science)EventFamily suidaeFoundationsGenerationsHeartHeart TransplantationHeart failureHeterogeneityHumanIncidenceIndividualInfarctionIon ChannelLifeLinkMeasuresMediatingMiniature SwineModelingMolecular BiologyMuscle CellsMyocardial InfarctionMyocardiumNerveNeurotransmittersNorepinephrinePatch-Clamp TechniquesPersonsPreventionPropertyRecoveryRegulationRoleTechniquesTestingTherapeuticTissue SurvivalTissuesTransplantationVasoactive Intestinal PeptideVentricularVentricular ArrhythmiaVisionautonomic nerveelectrical propertyexperimental studyhealingheart electrical activityimmunocytochemistryimprovedneuropeptide Yneuroregulationpharmacologicpreventprogramsresponsesudden cardiac deathtranslational study
项目摘要
PROJECT SUMMARY/ABSTRACT - Project 2
Sudden cardiac death (SCD) describes the abrupt onset of ventricular arrhythmias that kills more Americans
than any other disease. These life-threatening changes in electrical activity are most often observed in people
who have suffered a prior myocardial infarction (MI). Unfortunately, our ability to prevent SCD is limited by an
incomplete understanding of what actually triggers the underlying arrhythmias. The surviving tissue
surrounding the infarcted area of the heart, known as the border zone, is the primary sight of reentrant
electrical activity that sustains these events. Electrical heterogeneities in myocytes found in the border zone
and more remote areas of the myocardium create a substrate for reentry. However, the generation of
arrhythmias associated with SCD is also linked to an increase in sympathetic tone and a decrease in
parasympathetic tone. In fact, chronic vagal nerve stimulation (cVNS) has been shown to reduce the incidence
of ventricular arrhythmias following an MI. Yet, it is not known how myocytes found in different areas of the
infarcted heart respond to autonomic neurotransmitters such as norepinephrine (NE) and acetylcholine (ACh).
Furthermore, there is evidence the incidence of arrhythmias is also affected by the release of co-transmitters
such as neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). Our working hypothesis is that the
sympathetic neurotransmitters NE and NPY, as well as the parasympathetic neurotransmitters ACh and VIP,
alter the arrhythmogenic potential of the infarcted heart by regulating electrical heterogeneity as well as
triggered activity in different areas. In this Project, we will address the following questions: 1) how do NPY and
VIP affect the electrical properties of ventricular myocytes, 2) do sympathetic and parasympathetic
neurotransmitters affect electrical heterogeneity and triggered activity of myocytes in the border zone and
remote areas of the infarcted heart differently, and 3) does cVNS reduce arrhythmogenesis by remodeling the
electrical and pharmacological properties of myocytes in the infarcted heart. A combination of single cell
electrophysiology, molecular biology, immunocytochemistry, and biochemical techniques will be used to
answer these questions. Changes occurring at the cellular level identified in this Project will be integrated with
information about changes in the distribution and function of autonomic nerves observed at the whole heart
level in Projects 2 and 3 of this Program Project by using a computational modeling approach to investigate the
mechanistic basis for autonomic regulation of arrhythmias. The results of this project will provide the foundation
from which the efficacy of targeted neuromodulation can be mechanistically assessed, leading to improved
therapeutic strategies for preventing SCD.
项目摘要/摘要--项目2
心脏性猝死(SCD)指的是导致更多美国人死亡的室性心律失常的突然发作
比其他任何疾病都要好。这些危及生命的电活动变化最常在人身上观察到
有心肌梗死(MI)史的患者。不幸的是,我们预防SCD的能力受到
对真正引发潜在心律失常的原因了解不够充分。幸存的组织
围绕着心脏梗死区,称为交界区,是折返者的主要视线。
维持这些事件的电活动。在交界区发现肌细胞的电异质性
而心肌更偏远的区域为再入创造了一个底物。然而,这一代
与SCD相关的心律失常也与交感神经张力增加和
副交感神经音调。事实上,慢性迷走神经刺激(CVNS)已经被证明可以减少这种情况的发生。
心肌梗塞后的室性心律失常。然而,目前尚不清楚心肌细胞是如何在大脑的不同区域发现的。
心肌梗死对去甲肾上腺素(NE)和乙酰胆碱(ACh)等自主神经递质有反应。
此外,有证据表明,心律失常的发生率也受到共同递质释放的影响。
如神经肽Y(NPY)和血管活性肠肽(VIP)。我们的工作假设是
交感神经递质NE和NPY以及副交感神经递质ACh和VIP,
通过调节电的异质性改变梗塞心脏的致心律失常潜能
引发了不同地区的活动。在这个项目中,我们将解决以下问题:1)NPY和
血管活性肠肽影响心室肌细胞的电特性,2)交感神经和副交感神经
神经递质影响交界区和交界区肌细胞的电异质性和触发活动
3)CVN是否通过重塑心脏节律减少心律失常的发生?
心肌梗死后心肌细胞的电学和药理学特性。单个细胞的组合
将使用电生理学、分子生物学、免疫细胞化学和生化技术来
回答这些问题。在本项目中确定的蜂窝级别发生的变化将与
关于在整个心脏观察到的自主神经分布和功能变化的信息
在本计划项目的项目2和项目3中使用计算建模方法来调查
心律失常自主调节的机制基础。本项目的成果将为今后的工作奠定基础
由此可以机械地评估靶向神经调节的有效性,从而导致改善
预防SCD的治疗策略。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
ROBERT D HARVEY其他文献
ROBERT D HARVEY的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('ROBERT D HARVEY', 18)}}的其他基金
SUR Transmembrane Domain in K(ATP) Channel Function
K(ATP) 通道功能中的 SUR 跨膜结构域
- 批准号:
7057268 - 财政年份:2002
- 资助金额:
$ 39.03万 - 项目类别:
Muscarinic Signaling Pathways Affecting Cardiac Channels
影响心脏通道的毒蕈碱信号通路
- 批准号:
6638825 - 财政年份:2001
- 资助金额:
$ 39.03万 - 项目类别:
Muscarinic Signaling Pathways Affecting Cardiac Channels
影响心脏通道的毒蕈碱信号通路
- 批准号:
6750170 - 财政年份:2001
- 资助金额:
$ 39.03万 - 项目类别:
Muscarinic Signaling Pathways Affecting Cardiac Channels
影响心脏通道的毒蕈碱信号通路
- 批准号:
6368360 - 财政年份:2001
- 资助金额:
$ 39.03万 - 项目类别:
相似国自然基金
单双相动作电位忆阻神经元与基本类脑逻辑计算研究
- 批准号:QN25F010035
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
神经系统中动作电位双稳传导研究
- 批准号:12375033
- 批准年份:2023
- 资助金额:52 万元
- 项目类别:面上项目
与痛觉相关的动作电位传导失败的动力学与调控机制
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
帕金森病中NMDA受体对黑质多巴胺能神经元簇状放电活动的影响及机制研究
- 批准号:32000795
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
YAP通路调控Nav1.3表达在三叉神经痛异位冲动形成中的作用机制
- 批准号:82001184
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
IP3R1在成年小鼠心室传导系统中的作用及机制研究
- 批准号:31971045
- 批准年份:2019
- 资助金额:58.0 万元
- 项目类别:面上项目
神经元离子通道-动作电位-量子化分泌关系研究
- 批准号:31930061
- 批准年份:2019
- 资助金额:303 万元
- 项目类别:重点项目
仿生味觉自适应柔性纳米电极阵列构建研究
- 批准号:61901469
- 批准年份:2019
- 资助金额:24.5 万元
- 项目类别:青年科学基金项目
晚钠电流通过CaMK-II调节跨壁胞内钙离子分布在心肌缺血再灌注心律失常中的作用及机制研究
- 批准号:81900300
- 批准年份:2019
- 资助金额:20.0 万元
- 项目类别:青年科学基金项目
利用膜电位探针研究电位在轴突和树突上的产生和传播
- 批准号:81971679
- 批准年份:2019
- 资助金额:59.0 万元
- 项目类别:面上项目
相似海外基金
Kilohertz volumetric imaging of neuronal action potentials in awake behaving mice
清醒行为小鼠神经元动作电位的千赫兹体积成像
- 批准号:
10515267 - 财政年份:2022
- 资助金额:
$ 39.03万 - 项目类别:
Signal processing in horizontal cells of the mammalian retina – coding of visual information by calcium and sodium action potentials
哺乳动物视网膜水平细胞的信号处理 â 通过钙和钠动作电位编码视觉信息
- 批准号:
422915148 - 财政年份:2019
- 资助金额:
$ 39.03万 - 项目类别:
Research Grants
CAREER: Resolving action potentials and high-density neural signals from the surface of the brain
职业:解析来自大脑表面的动作电位和高密度神经信号
- 批准号:
1752274 - 财政年份:2018
- 资助金额:
$ 39.03万 - 项目类别:
Continuing Grant
Development of Nanosheet-Based Wireless Probes for Multi-Simultaneous Monitoring of Action Potentials and Neurotransmitters
开发基于纳米片的无线探针,用于同时监测动作电位和神经递质
- 批准号:
18H03539 - 财政年份:2018
- 资助金额:
$ 39.03万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Population Imaging of Action Potentials by Novel Two-Photon Microscopes and Genetically Encoded Voltage Indicators
通过新型双光子显微镜和基因编码电压指示器对动作电位进行群体成像
- 批准号:
9588470 - 财政年份:2018
- 资助金额:
$ 39.03万 - 项目类别:
Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics
通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描,增强多束周围神经复合动作电位的定量成像
- 批准号:
10009724 - 财政年份:2018
- 资助金额:
$ 39.03万 - 项目类别:
Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics
通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描,增强多束周围神经复合动作电位的定量成像
- 批准号:
10467225 - 财政年份:2018
- 资助金额:
$ 39.03万 - 项目类别:
Fast high-resolution deep photoacoustic tomography of action potentials in brains
大脑动作电位的快速高分辨率深度光声断层扫描
- 批准号:
9423398 - 财政年份:2017
- 资助金额:
$ 39.03万 - 项目类别:
Noval regulatory mechanisms of axonal action potentials
轴突动作电位的新调节机制
- 批准号:
16K07006 - 财政年份:2016
- 资助金额:
$ 39.03万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
NeuroGrid: a scalable system for large-scale recording of action potentials from the brain surface
NeuroGrid:用于大规模记录大脑表面动作电位的可扩展系统
- 批准号:
9357409 - 财政年份:2016
- 资助金额:
$ 39.03万 - 项目类别: