Stable Isotope Approaches to the Understanding of Potassium Homeostasis
稳定同位素方法了解钾稳态
基本信息
- 批准号:10431555
- 负责人:
- 金额:$ 26.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-15 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAffectAldosteroneAnimalsBiochemicalBloodBrainBuffersCardiovascular PhysiologyCardiovascular systemCellsChronicCollaborationsCommunicationDevelopmentDietary PotassiumElementsEpinephrineEquilibriumEventExcretory functionExerciseExtracellular FluidFutureGrantHalf-LifeHomeostasisHormonesIn VitroIncubatedIndividualInductively Coupled Plasma Mass SpectrometryInsulinIntakeIntracellular FluidIsotopesKidneyLeadLifeLiquid substanceMeasurementMeasuresMethodologyMethodsModelingMolecularMuscleNa(+)-K(+)-Exchanging ATPaseNatureNeurophysiology - biologic functionOrganPancreasPatientsPlasmaPlayPotassiumPotassium ChannelRadioactive TracersRadioactivityRattusRegulationRoleSamplingSignal TransductionSkeletal MuscleTechnologyTextTimeTissuesTracerUniversitiesVariantWorkanalytical methodextracellularheart functionhyperkalemiain vivoinnovationneuromuscular functionnovel strategiesnovel therapeuticsstable isotopetool
项目摘要
Project Summary
Potassium (K+) homeostasis is critical for normal cardiovascular and neuromuscular function, and
disturbances in K+ homeostasis (e.g., hyperkalemia) can lead to life-threatening cardiovascular events.
Extracellular K+ homeostasis is maintained by renal and extrarenal mechanisms. The kidneys have a remarkable
capacity to regulate K+ excretion to match K+ intake, playing the major role in maintaining chronic K+ balance. In
addition, extrarenal tissues (mainly skeletal muscle, the major K+ store) provide K+ buffering capacity by shifting
K+ between the extracellular and intracellular fluids. Furthermore, gut sensing of dietary K+ appears to generate
signals for regulating renal K+ excretion and extrarenal K+ shift. Thus, extracellular K+ homeostasis involves
multiple organs and tissues, their adaptation to dietary K+ intake, and crosstalk among them. Despite marked
progress in this field in recent decades, many critical issues concerning K+ homeostatic mechanisms remain
unresolved due to a lack of appropriate methodology. A main limitation in studies of extracellular K+ homeostasis
is an inability to quantify K+ fluxes in vivo. Although previous studies quantified K+ fluxes using 86Rb, a radioactive
tracer for K+, radioactivity exposure and short half-life of 86Rb have limited its use to in vitro studies. Stable
isotopes of a wide range of elements have been used to quantify fluxes of various substrates or blood
constituents in vivo. However, in spite of the existence of two stable isotopes of K+ in nature (39K, 93.3% and 41K,
6.7%), this approach has not been applied to the study of K+ homeostasis in vivo due to analytical limitations.
Dr. John Higgins, a geochemist at Princeton University, developed analytical methods for determining the ratio
of stable K+ isotopes (41K/39K) in natural samples using inductively coupled plasma mass spectrometry. This
state-of-the-art technology provides the opportunity to determine K+ fluxes in vivo using stable isotopes (i.e.,
without using radioactive tracers). The objective of the current proposal is to develop and validate this new
approach for estimating whole-body K+ fluxes in vivo and extend it to assess K+ transport activities in individual
tissues. If successfully developed, these new cutting-edge approaches will open new doors to answering
important questions and filling gaps in K+ homeostatic mechanisms in vivo. These stable isotope approaches
will be highly innovative, as they allow whole-body and in vitro K+ flux analyses that were infeasible with any
conventional approaches, including those with 86Rb.
项目摘要
钾(K+)稳态对正常心血管和神经肌肉功能至关重要,
K+稳态的紊乱(例如,高钾血症)可导致危及生命的心血管事件。
细胞外K+稳态由肾和肾外机制维持。肾脏有一个显著的
调节K+排泄以匹配K+摄入的能力,在维持慢性K+平衡中起主要作用。在
此外,肾外组织(主要是骨骼肌,主要的K+库)通过转移提供K+缓冲能力。
细胞外液和细胞内液之间的K+。此外,肠道对膳食K+的感知似乎会产生
调节肾K+排泄和肾外K+转移的信号。因此,细胞外K+稳态涉及
多器官和组织,它们对膳食K+摄入的适应,以及它们之间的串扰。尽管标记
尽管近几十年来这一领域的研究取得了很大进展,但有关K+稳态机制的许多关键问题仍然存在
由于缺乏适当的方法,这一问题尚未得到解决。细胞外钾稳态研究的一个主要局限
不能定量体内K+通量。虽然先前的研究使用放射性同位素86 Rb定量K+通量,
K+示踪剂、放射性暴露和86 Rb的短半衰期限制了其在体外研究中的使用。稳定
广泛范围的元素的同位素已被用于量化各种基质或血液的通量
体内成分。然而,尽管自然界中存在两种稳定的K+同位素(39 K,93.3%和41 K,
6.7%),由于分析限制,该方法尚未应用于体内K+稳态的研究。
博士普林斯顿大学的地球化学家约翰·希金斯(John Higgins)开发了确定比例的分析方法
用电感耦合等离子体质谱法测定了天然样品中稳定的钾同位素(41 K/39 K)。这
现有技术提供了使用稳定同位素在体内测定K+通量的机会(即,
不使用放射性示踪剂)。当前提案的目标是开发和验证这一新的
一种估算体内全身K+通量的方法,并将其扩展到评估个体K+转运活动
组织中如果开发成功,这些新的尖端方法将为回答
重要的问题和填补空白的K+体内稳态机制。这些稳定同位素方法
将是高度创新的,因为它们允许全身和体外K+通量分析,这是不可行的任何
常规方法,包括使用86 Rb的方法。
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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{{ truncateString('JANG H. YOUN', 18)}}的其他基金
Stable Isotope Approaches to the Understanding of Potassium Homeostasis
稳定同位素方法了解钾稳态
- 批准号:
10592405 - 财政年份:2022
- 资助金额:
$ 26.17万 - 项目类别:
Soluble epoxide hydrolase: assessment of in vivo activity and regulation by gut microbiota
可溶性环氧化物水解酶:体内活性评估和肠道微生物群的调节
- 批准号:
10204615 - 财政年份:2021
- 资助金额:
$ 26.17万 - 项目类别:
Soluble epoxide hydrolase: assessment of in vivo activity and regulation by gut microbiota
可溶性环氧化物水解酶:体内活性评估和肠道微生物群的调节
- 批准号:
10580709 - 财政年份:2021
- 资助金额:
$ 26.17万 - 项目类别:
Soluble epoxide hydrolase: assessment of in vivo activity and regulation by gut microbiota
可溶性环氧化物水解酶:体内活性评估和肠道微生物群的调节
- 批准号:
10377514 - 财政年份:2021
- 资助金额:
$ 26.17万 - 项目类别:
A Novel Mechanism of HPA Axis Activation: Role of Nicotinic Acid Receptor in the
HPA 轴激活的新机制:烟酸受体在
- 批准号:
8031153 - 财政年份:2011
- 资助金额:
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Mechanism of HPA Axis Activation: Role of Nicotinic Acid Receptor in the Brain
HPA 轴激活机制:烟酸受体在大脑中的作用
- 批准号:
8225242 - 财政年份:2011
- 资助金额:
$ 26.17万 - 项目类别:
REGULATION OF RENAL K+ EXCRETION BY GUT FACTOR
肠道因子对肾 K 排泄的调节
- 批准号:
7638485 - 财政年份:2008
- 资助金额:
$ 26.17万 - 项目类别:
REGULATION OF RENAL K+ EXCRETION BY GUT FACTOR
肠道因子对肾 K 排泄的调节
- 批准号:
7528744 - 财政年份:2008
- 资助金额:
$ 26.17万 - 项目类别:
ROLE OF SENSING OF K+ INTAKE IN K+ HOMEOSTASIS
钾摄入量传感在钾稳态中的作用
- 批准号:
6708525 - 财政年份:2004
- 资助金额:
$ 26.17万 - 项目类别:
ROLE OF SENSING OF K+ INTAKE IN K+ HOMEOSTASIS
钾摄入量传感在钾稳态中的作用
- 批准号:
6841687 - 财政年份:2004
- 资助金额:
$ 26.17万 - 项目类别:
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