课题基金 / 基金详情

Skeletal Muscle. Ca Release Control Inside the Sarcoplasmic Reticulum.

Skeletal Muscle. Ca Release Control Inside the Sarcoplasmic Reticulum.
骨骼肌。
批准号:
8464002
负责人:
Eduardo Rios
金额:
$29.39万
依托单位国家:
美国
项目类别:
财政年份:
2003
资助国家:
美国
项目状态:
已结题
起止时间:
2003-07-01 至 2015-04-30

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英文摘要
DESCRIPTION (provided by applicant): Ca2+ signaling is a universal language used by cells to react and change. In skeletal muscle its patterns of interest cover multiple time scales: milliseconds -Ca2+ movements that determine contraction and relaxation-; seconds to minutes -when sustained activity may lead to myogenic fatigue- and hours to weeks -patterns that cause changes in gene expression and long-term adaptation-. This study is about inside its cellular store; its quantity, and its concentration, [Ca2+]SR, which conditions Ca2+ signals in every time scale. We ask (1) whether and how [Ca2+]SR controls Ca2+ release from the store, and (2) whether and how calsequestrin and triadin, two strategically located SR proteins, contribute to this control. A technical task, which we call "aim 0", is to image and measure [Ca2+]SR. This was accomplished in the current period and will continue in the next, using novel biosensors -molecules made by the cells themselves- and new hybrid monitors, consisting of high performance small synthetic sensors placed into cells manipulated to make special bio-anchors. To answer questions 1 and 2, we will respectively manipulate [Ca2+]SR while we measure it (aim 1) and force cells to change their endowment of calsequestrin and triadin (aim 2). These goals are now feasible in living animals thanks to a DNA transfection method that works with every protein and can be used also to prevent their synthesis. We propose that [Ca2+]SR -which decays when muscles fatigue- is sustained by SOCE, a universal Ca2+ entry pathway, crucial for mobilizing transcription factors that control gene expression. Using SOCE measures developed in the first period, we propose as aim 3 to define the role of newly discovered molecules of SOCE in the control of [Ca2+]SR. These molecules could be bulwarks against fatigue, and provide powerful tools for experimental alterations of [Ca2+]SR in iterative approaches to the main questions. Ca2+ signals deteriorate in disease, fatigue and aging. Fast Ca2+ signals fail in diseases like hypo-PP, MH susceptibility and central core and minicore, as well as in ageing muscle. Mid-range signaling is affected in fatigue and in an MH-like phenotype of mice lacking calsequestrin. Diseases of long term Ca2+ signals, which show striking parallels in muscle and the immune system, include SCID, a familial immune defect that combines loss of SOCE in lymphocytes and a myogenic myopathy. Our work will advance understanding of these deficits by evaluating roles of specific molecules and their interactions. While only fatigue will be specifically addressed in the present project, questions on the relationships among deficits of function, the intricate pathophysiology and the rational design of therapeutic corrections will be addressed better as we understand what controls stored calcium, and what the stored calcium controls.
期刊论文(26)
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科研奖励(0)
会议论文
DOI: 10.1085/jgp.200409105
发表时间: 2004
期刊: The Journal of general physiology
影响因子: --
作者: [Zhou,Jingsong, Launikonis,BradleyS, Ríos,Eduardo, Brum,Gustavo]
通讯作者: Brum,Gustavo
DOI: 10.1021/cb800258g
发表时间: 2009-03-20
期刊: ACS CHEMICAL BIOLOGY
影响因子: 4
作者: [Bannwarth, Michael, Correa, Ivan R., Jr., Sztretye, Monika, Pouvreau, Sandrine, Fellay, Cindy, Aebischer, Annina, Royer, Leandro, Ríos, Eduardo, Johnsson, Kai]
通讯作者: Johnsson, Kai
Life and death of a cardiac calcium spark.
心脏钙火花的生与死。
DOI: 10.1085/jgp.201311034
发表时间: 2013-09
期刊: The Journal of general physiology
影响因子: --
作者: [Stern MD, Ríos E, Maltsev VA]
通讯作者: Maltsev VA
On an early demonstration of the cell boundary theorem.
关于细胞边界定理的早期证明。
DOI: 10.1007/s12576-012-0245-4
发表时间: 2013
期刊: The journal of physiological sciences : JPS
影响因子: --
作者: [Ríos,Eduardo]
通讯作者: Ríos,Eduardo
10
    Dual Confocal Microscopic Scanner
    • 批准号:
      7389185
    • 项目类别:
    • 资助金额:
      $50.0万
    • 财政年份:
      2008
    • 负责人:
      Eduardo Rios
    • 依托单位:
    Skeletal Muscle. Ca Release Control Inside the Sarcoplasmic Reticulum.
    • 批准号:
      8268539
    • 项目类别:
    • 资助金额:
      $30.71万
    • 财政年份:
      2003
    • 负责人:
      Eduardo Rios
    • 依托单位:
    Skeletal Muscle. Ca2+ release control inside the SR
    • 批准号:
      6678047
    • 项目类别:
    • 资助金额:
      $33.74万
    • 财政年份:
      2003
    • 负责人:
      Eduardo Rios
    • 依托单位:
    Skeletal Muscle. Ca2+ release control inside the SR
    • 批准号:
      7256325
    • 项目类别:
    • 资助金额:
      $29.29万
    • 财政年份:
      2003
    • 负责人:
      Eduardo Rios
    • 依托单位:
    海外基金