Functional interaction between cardiac Na channels and KATP channels
心脏 Na 通道和 KATP 通道之间的功能相互作用
基本信息
- 批准号:10160950
- 负责人:
- 金额:$ 68.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-07 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:ANK3 geneAction PotentialsAdherens JunctionAnimal ModelAnkyrinsAreaBindingBinding SitesBiochemistryCardiacCardiac Electrophysiologic TechniquesCardiac MyocytesCardiovascular systemCaveolaeCell AdhesionCell CommunicationCellsCharacteristicsCodeComplexCouplesCouplingDataDiseaseEventFluorescence MicroscopyGenesHeartHeart RateHybridsInheritedIntercalated discInvestigationIon ChannelKnowledgeLateralMediatingMembraneMicroscopyModelingMolecularMolecular BiologyMuscle CellsNa(+)-K(+)-Exchanging ATPasePeptidesPhysiologicalProteinsResearch PersonnelResolutionRoleRyanodine ReceptorsShapesSiteSmall Interfering RNAStressSurfaceSystemTechniquesTestingTimeVentriculardensitydesigngenetic variantimaging modalityinnovationinsightischemic injurymedical schoolsnanometerpatch clampresponsescanning ion conductance microscopysyntrophinvoltage
项目摘要
SUMMARY
Cardiac Na+ channels and KATP channels are generally thought to have very different roles in cardiac
electrophysiology. They do, however, share certain characteristics such as being expressed at higher levels at
the intercalated disk compared to the lateral membranes and they coexist with desmosomal proteins. Our new
data demonstrate that cardiac KATP channels interact with Na+ channels (and with the Na+/K+ ATPase). This
proposal will utilize innovate super-resolution microscopy techniques and patch clamping to examine the
interaction between Na+ channels and KATP channels. We will identify the membrane subdomains where
interaction occurs, the molecular mechanisms responsible for interaction and the functional consequences of
interactions. The overall hypotheses is that interaction is particularly prominent at membrane domains at the
ICD, that interaction is mediated by specific binding sites in ankyrin-G, and that interaction leads to functional
coupling between Na+ channels and KATP channels (via the Na+/K+ ATPase). In a first Aim, we will localize Na+
channels and KATP channels with nanometer precision to membrane subdomains in the lateral membrane (e.g.
t-tubules, caveolae, etc.) as well as membrane subdomains at the intercalated disk (e.g. hybrid adhering
junctions). A role for ankyrins in targeting channels to these domains will be investigated with siRNA
approaches. In a second Aim, we will investigate the molecular mechanisms involved in interaction, testing the
hypothesis that Na+ channels and KATP channels bind to similar sites on ankyrins. We will also test the
functional consequences of interaction of Na+ channels and KATP channels. These studies will significantly
move forward our understanding of Na+ channel and KATP channel and function in the cardiovascular system,
and more generally, advance our knowledge on how channel systems in ventricular myocytes physically and
functionally interact.
总结
心脏Na+通道和KATP通道通常被认为在心脏中具有非常不同的作用。
电生理学然而,它们确实具有某些共同的特征,例如在更高的水平上表达,
它们与桥粒蛋白共存。我们的新
数据表明心脏KATP通道与Na+通道(和Na+/K+ ATP酶)相互作用。这
该提案将利用创新的超分辨率显微镜技术和膜片钳来检查
Na+通道和KATP通道之间的相互作用。我们将确定膜子域,
相互作用的发生,负责相互作用的分子机制和相互作用的功能后果,
交互.总的假设是,相互作用是特别突出的膜结构域在
ICD,即相互作用是由特异性结合位点介导的,在锚-G,和相互作用导致功能性
Na+通道和KATP通道之间的偶联(通过Na+/K+ ATP酶)。在第一个目标中,我们将定位Na+
通道和KATP通道以纳米精度连接到侧膜中的膜子域(例如,
t-小管、小窝等)以及在插入盘处的膜子域(例如
junctions)。锚蛋白在靶向这些结构域的通道中的作用将用siRNA进行研究
接近。在第二个目标中,我们将研究相互作用中涉及的分子机制,测试
假设Na+通道和KATP通道结合锚蛋白上的相似位点。我们还将测试
Na+通道和KATP通道相互作用的功能后果。这些研究将大大
进一步了解Na+通道和KATP通道在心血管系统中的作用,
更广泛地说,推进了我们对心室肌细胞中通道系统的物理和
功能性互动。
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)
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William A Coetzee其他文献
Sources of Activator Calcium in the Developing Rabbit Heart
- DOI:
10.1203/00006450-199904020-00352 - 发表时间:
1999-04-01 - 期刊:
- 影响因子:3.100
- 作者:
Avani Patel;Peter S Haddock;William A Coetzee;Michael Artman - 通讯作者:
Michael Artman
Effects of Cooling Rate on Contractile Function of Ventricular Myocytes Isolated from Newborn Piglets ♦ 107
- DOI:
10.1203/00006450-199804001-00128 - 发表时间:
1998-04-01 - 期刊:
- 影响因子:3.100
- 作者:
Hanna M El-Khouri;Peter S Haddock;Jeffrey Miller;Aubrey C Galloway;William A Coetzee;Michael Artman - 通讯作者:
Michael Artman
William A Coetzee的其他文献
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{{ truncateString('William A Coetzee', 18)}}的其他基金
Roles of Endothelial and Smooth Muscle KATP Channels in Myocardial Ischemic Injury
内皮和平滑肌 KATP 通道在心肌缺血性损伤中的作用
- 批准号:
10839729 - 财政年份:2023
- 资助金额:
$ 68.26万 - 项目类别:
Tweety proteins: their roles in pericytes and macrophages
Tweety 蛋白:它们在周细胞和巨噬细胞中的作用
- 批准号:
10665494 - 财政年份:2023
- 资助金额:
$ 68.26万 - 项目类别:
Functional interaction between cardiac Na channels and KATP channels
心脏 Na 通道和 KATP 通道之间的功能相互作用
- 批准号:
10399543 - 财政年份:2020
- 资助金额:
$ 68.26万 - 项目类别:
Functional interaction between cardiac Na channels and KATP channels
心脏 Na 通道和 KATP 通道之间的功能相互作用
- 批准号:
10613516 - 财政年份:2020
- 资助金额:
$ 68.26万 - 项目类别:
Roles of Endothelial and Smooth Muscle KATP Channels in Myocardial Ischemic Injury
内皮和平滑肌 KATP 通道在心肌缺血性损伤中的作用
- 批准号:
9914670 - 财政年份:2019
- 资助金额:
$ 68.26万 - 项目类别:
Roles of Endothelial and Smooth Muscle KATP Channels in Myocardial Ischemic Injury
内皮和平滑肌 KATP 通道在心肌缺血性损伤中的作用
- 批准号:
10308702 - 财政年份:2019
- 资助金额:
$ 68.26万 - 项目类别:
Roles of Endothelial and Smooth Muscle KATP Channels in Myocardial Ischemic Injury
内皮和平滑肌 KATP 通道在心肌缺血性损伤中的作用
- 批准号:
10064008 - 财政年份:2019
- 资助金额:
$ 68.26万 - 项目类别:
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