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MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY

MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
肾脏 ROMK 通道的调节和调节
批准号:
6635131
负责人:
Wenhui Wang
金额:
$24.65万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-03-01 至 2005-01-31

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中文摘要
翻译
描述:(逐字摘自申请表)提案的总体目标 (IRPG#3)旨在探索ROMK激素调节的分子机制 并明确ROMK通道在心尖K通道形成中的作用 在粗大的上肢(TAL)。ROMK通道共享关键的生物物理 天然小电导ATP敏感性钾通道(SKatp)的特性 在肺泡灌洗液和收集管中。然而,SKSTP的监管机制 由于SKatp的密度很低,因此对TAL中的SKatp还没有完全了解。 这一困难现在可以克服,因为初步结果表明 在小鼠TAL中,心尖K通道的密度显著 通过添加Forsklin或去除细胞外钙而增加。 因此,具体目标1的第一个目标是研究生物物理性质 在小鼠TAL的心尖K通道中。这些信息将是重要的 为进一步研究ROMK通道在心尖K形成中的作用 ROMK&8209;基因敲除小鼠可用时的频道。第二个目标是 探讨加压素受体和加压素之间相互作用的假说 钙敏感受体(CAR)介导的作用在决定 小鼠TAL中心尖K通道的活动。 特异目的2的目标是研究激酶锚定蛋白的作用。 在介导PKA和PKC调节ROMK通道功能中的作用 磷酸化。具体目标3的目标是通过以下方式研究该机制 其中PGE2调节TAL中的心尖K通道。前列腺素E_2的作用有 与巴特综合征的相关性,其中高前列腺素血症和 抑制前列腺素的产生部分逆转了生理上的 TAL功能受损的后果。
英文摘要
DESCRIPTION: (verbatim from application) The overall goals of the proposal (IRPG#3) are to explore the molecular mechanisms of hormonal regulation of ROMK channels and to define the role of ROMK channels in forming apical K + channels in the thick ascending limb (TAL). ROMK channels share the key biophysical properties with the native small-conductance ATP-sensitive K+ channel (SKatp) in the TAL and collecting duct. However, mechanisms by which SKstp is regulated in the TAL are not completely understood since the density of the SKatp is low. This difficulty can now be overcome since preliminary results have demonstrated that in the mouse TAL the density of the apical K channels is significantly increased by either adding forskolin or removal of extracellular Ca2+. Thus, the first goal of Specific Aim 1 is to study the biophysical properties of the apical K+ channels in the mouse TAL. The information will be important for further studying the role of ROMK channels in forming the apical K+ channels when the ROMK‑knockout mice are available. The second goal is to explore the hypothesis that interaction between the vasopressin receptor and the Ca2+-sensing receptor (CaR)-mediated action plays a key role in determining the activity of the apical K+ channels in the mouse TAL. The goal of Specific Aim 2 is to examine the role of kinase anchoring proteins in mediating the effect of PKA and PKC in modulating ROMK channel function and phosphorylation. The goal of Specific Aim 3 is to investigate the mechanism by which PGE2 regulates the apical K+ channels in the TAL. The effect of PGE2 has relevance to Bartter's Syndrome where hyperprostaglandinemia is prominent and inhibition of prostaglandin production reverses partially the physiological consequences of impaired TAL function.
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Epoxyeicosatrienoic Acids Regulate Na Transport in CCD
  • 批准号:
    7137831
  • 项目类别:
  • 资助金额:
    $30.6万
  • 财政年份:
    2005
  • 负责人:
    Wenhui Wang
  • 依托单位:
REGULATION OF MTAL FUNCTION BY 20-HETE, NO, AND CO
  • 批准号:
    6796315
  • 项目类别:
  • 资助金额:
    $31.48万
  • 财政年份:
    2003
  • 负责人:
    Wenhui Wang
  • 依托单位:
REGULATION OF MTAL FUNCTION BY 20-HETE, NO, AND CO
  • 批准号:
    6653344
  • 项目类别:
  • 资助金额:
    $31.48万
  • 财政年份:
    2002
  • 负责人:
    Wenhui Wang
  • 依托单位:
MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
  • 批准号:
    6285695
  • 项目类别:
  • 资助金额:
    $23.92万
  • 财政年份:
    2001
  • 负责人:
    Wenhui Wang
  • 依托单位:
海外基金