Ion Selective Quantum Dots for Intracellular Mapping of Sodium Sparks in Cardiac

用于心脏钠火花细胞内图谱的离子选择性量子点

基本信息

  • 批准号:
    8111406
  • 负责人:
  • 金额:
    $ 25.29万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-05-01 至 2013-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Ion-selective quantum dots (ISQDs) are ion-selective polymer-based optical nanosensors that incorporate quantum dots (QDs) into the core of the sensor. A sodium-selective ISQD measures sodium over the range of 1mM to 1 M with 100 fold selectivity over potassium and a resolution of 80 5M. Ion-selective quantum dots consist of a quantum dot, a pH sensitive dye, and an ion-selective polymer. Selective ion extraction into the polymer matrix causes a pH change inside the matrix therefore changing the absorbance properties of the pH sensitive dye. The change of absorbance attenuates the intensity of the quantum dot by directly absorbing its fluorescence emission. Our hypothesis is that using ISQDs to map the spatial distribution of intracellular sodium will reveal a heterogeneous distribution of ion activity during the action potential of a cardiac cell. We base our hypothesis on the following: First, ISQDs are the only sodium probes available that are selective over physiological levels of potassium, photostable, and biocompatible. Second, it has been shown that fluxes of ions at the opening of an ion channel create localized regions of high ion concentrations, or calcium sparks . Because of the nature of the channel sodium sparks should be present at the opening of sodium channels, however there are very few documented cases in the literature. We believe that using better tools for sodium imaging, such as ISQDs, will provide a wealth of information on this little known process. The specific aims of this application period are: 1. To tailor ISQDs to be compatible with the analytical requirements of measuring sodium in an intracellular environment. A robust sensor must demonstrate optimal results in the following categories: physiologically relevant dynamic range, leaching/lifetime of sensors, and size. 2. To validate the response of ISQDs to sodium in the intracellular environment. ISQDs must show a response to changes in sodium in the intracellular environment that are comparable to those achieved in solution studies in Specific Aim 1. Validation will be performed using simultaneous patch clamp and optical recording in a well-defined cell system. Additionally, a comparison to patch-clamp alone (no ISQDs) and CoroNa dyes will be performed. A dose response to the effects of known channel blockers will also be carried out. 3. To map the spatial distribution of sodium in cardiac myocytes. Sodium fluxes through ion channels in the outer membrane lead to inhomogeneous distributions of sodium concentration in the cell, at least during the duration of the open channel. Sodium sparks will be identified in cardiac myocytes, and will be evaluated for effects to sodium channel blockers. PUBLIC HEALTH RELEVANCE: The ultimate goal of this application is to develop and use a new intracellular imaging tool, Ion- Selective Quantum Dots to map sodium microdomains in cardiac cells. These probes will provide crucial information on ion channel distribution that is not available with current tools. Ultimately, this tool will provide new knowledge of cardiac action potentials and possibly lead to the prevention of fatal arrhythmias in diseases such as Long QT syndrome.
描述(申请人提供):离子选择性量子点(ISQD)是离子选择性聚合物为基础的光学纳米传感器,它将量子点(QD)结合到传感器的核心中。钠选择性ISQD测量钠的范围为1 mm到1 M,选择性是钾的100倍,分辨率为80 5M。离子选择性量子点由量子点、pH敏感染料和离子选择性聚合物组成。选择性离子萃取进入聚合物基质会引起基质内部的pH变化,从而改变对pH敏感的染料的吸收特性。吸光度的变化通过直接吸收其荧光发射来衰减量子点的强度。我们的假设是,使用ISQD来绘制细胞内钠的空间分布将揭示心肌细胞动作电位期间离子活性的不同分布。我们的假设建立在以下基础上:首先,ISQD是唯一一种对生理水平的钾具有选择性、光稳定和生物相容的钠探针。其次,已经证明,离子通道打开时的离子流量会产生高离子浓度的局部区域,即钙火花。由于钠离子通道的性质,钠离子离子应该出现在钠离子通道的开口处,然而文献中记录在案的病例很少。我们相信,使用更好的钠成像工具,如ISQD,将提供关于这一鲜为人知的过程的丰富信息。本申请期的具体目标是:1.量身定做ISQD,以适应细胞内环境中钠离子测量的分析要求。一个坚固的传感器必须在以下几个方面表现出最佳的结果:生理上相关的动态范围、传感器的浸出/寿命和尺寸。2.验证细胞内环境中ISQds对钠离子的响应。ISQD对细胞内环境中钠离子变化的响应必须与在特定目标1的溶液研究中达到的响应相当。验证将在定义良好的细胞系统中使用同步膜片钳和光学记录进行。此外,还将与膜片钳(无ISQD)和电晕染料进行比较。对已知的通道阻滞剂的作用也将进行剂量反应。3.绘制心肌细胞内钠离子的空间分布图。通过外膜离子通道的钠通量导致细胞内钠浓度的不均匀分布,至少在开放通道的持续时间内是这样。钠火花将在心肌细胞中被识别,并将被评估对钠通道阻滞剂的影响。 公共卫生相关性:这项应用的最终目标是开发和使用一种新的细胞内成像工具--离子选择性量子点来绘制心肌细胞中的钠微域。这些探测器将提供有关离子通道分布的关键信息,而目前的工具无法提供这些信息。最终,这一工具将提供心脏动作电位的新知识,并可能导致在长QT综合征等疾病中预防致命的心律失常。

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 }}

Heather A Clark其他文献

Heather A Clark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('Heather A Clark', 18)}}的其他基金

Circulating Red Blood Cell Based Nanosensors for Continuous, Real-Time Drug Monitoring
基于循环红细胞的纳米传感器,用于连续、实时药物监测
  • 批准号:
    10174441
  • 财政年份:
    2018
  • 资助金额:
    $ 25.29万
  • 项目类别:
Circulating Red Blood Cell Based Nanosensors for Continuous, Real-Time Drug Monitoring
基于循环红细胞的纳米传感器,用于连续、实时药物监测
  • 批准号:
    10062973
  • 财政年份:
    2018
  • 资助金额:
    $ 25.29万
  • 项目类别:
Optical Nanosensors Detect Neurotransmitter Release in the Peripheral Nervous System
光学纳米传感器检测周围神经系统中神经递质的释放
  • 批准号:
    10003578
  • 财政年份:
    2017
  • 资助金额:
    $ 25.29万
  • 项目类别:
Optical Nanosensors Detect Neurotransmitter Release in the Peripheral Nervous System
光学纳米传感器检测周围神经系统中神经递质的释放
  • 批准号:
    9746805
  • 财政年份:
    2017
  • 资助金额:
    $ 25.29万
  • 项目类别:
Polymer-Free Nanosensors To Visualize Biochemical Dynamics in Dendritic Spines
无聚合物纳米传感器可视化树突棘生化动力学
  • 批准号:
    8660103
  • 财政年份:
    2013
  • 资助金额:
    $ 25.29万
  • 项目类别:
Polymer-Free Nanosensors To Visualize Biochemical Dynamics in Dendritic Spines
无聚合物纳米传感器可视化树突棘生化动力学
  • 批准号:
    8588718
  • 财政年份:
    2013
  • 资助金额:
    $ 25.29万
  • 项目类别:
Ion Selective Quantum Dots for Intracellular Mapping of Sodium Sparks in Cardiac
用于心脏钠火花细胞内图谱的离子选择性量子点
  • 批准号:
    7451559
  • 财政年份:
    2008
  • 资助金额:
    $ 25.29万
  • 项目类别:
Ion Selective Quantum Dots for Intracellular Mapping of Sodium Sparks in Cardiac
用于心脏钠火花细胞内图谱的离子选择性量子点
  • 批准号:
    8074080
  • 财政年份:
    2008
  • 资助金额:
    $ 25.29万
  • 项目类别:
Ion Selective Quantum Dots for Intracellular Mapping of Sodium Sparks in Cardiac
用于心脏钠火花细胞内图谱的离子选择性量子点
  • 批准号:
    8260333
  • 财政年份:
    2008
  • 资助金额:
    $ 25.29万
  • 项目类别:
Ion Selective Quantum Dots for Intracellular Mapping of Sodium Sparks in Cardiac
用于心脏钠火花细胞内图谱的离子选择性量子点
  • 批准号:
    7619126
  • 财政年份:
    2008
  • 资助金额:
    $ 25.29万
  • 项目类别:

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 25.29万
  • 项目类别:
    Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 25.29万
  • 项目类别:
    Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 25.29万
  • 项目类别:
    Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 25.29万
  • 项目类别:
    Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 25.29万
  • 项目类别:
    Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 25.29万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 25.29万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 25.29万
  • 项目类别:
    Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 25.29万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 25.29万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了