Calcium signaling in airway smooth muscle in lung slices
肺切片气道平滑肌中的钙信号传导
基本信息
- 批准号:7272686
- 负责人:
- 金额:$ 30.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-09-01 至 2008-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAgonistAsthmaCalciumCalcium SignalingCaliberCharacteristicsConfocal MicroscopyDataEventFrequenciesIn SituLungMaintenanceMeasuresMediatingMuscle ContractionPreparationPropertyRangeRelaxationRestSignal TransductionSliceSmooth Muscle MyocytesStructureTestingTherapeuticairway hyperresponsivenessbaseinsightmouse modelrespiratory smooth muscleresponse
项目摘要
DESCRIPTION (provided by applicant): A characteristic of asthma is airway hyper-reactivity, a response acutely mediated by smooth muscle cell (SMC) contraction. SMC contractility is initiated by increases in intracellular calcium concentration ([Ca2+]i) but the mechanisms of Ca2+ signaling in airway SMCs and how these relate to changes in airway caliber are poorly understood. To address this problem, we have developed a unique lung slice preparation that retains many properties of the lung structure, and in which the Ca2+ signaling of the SMCs and the associated airway contraction or relaxation can be measured simultaneously with confocal microscopy. Our data shows that airway SMCs display a graded range of IP3-based Ca2+ signaling that consists of elemental Ca2+ signals, intracellular Ca2+ oscillations and Ca2+ waves and that these signals correlate with the establishment of resting airway tone as well as the initiation and maintenance of SMC and airway contraction.
Consequently, we hypothesize that the frequency of the Ca2+ signals in SMCs serves to regulate Ca2+ airway caliber. To test this idea, we plan to determine: 1) the Ca signaling mechanisms responsible for the Ca2+ establishment of resting airway tone by investigating the elemental Ca signaling and mechanism of spontaneous Ca2+ oscillations and contractions of airway SMCs, 2) if airway caliber is regulated by frequency-modulation (FM) mediated by Ca2+ oscillations, and 3) how Ca2+ signaling and contraction is altered in airway SMCs of mouse models for hyper-reactivity and asthma. By understanding the graded mechanisms of elemental Ca2+ signaling and Ca2+ oscillations in lung SMCs and how these events regulate SMC contractility and relate to airway caliber, we can gain the necessary insight needed to approach a therapeutic strategy for modulating airway hyper-reactivity.
描述(由申请人提供):哮喘的特征是气道高反应性,这种反应是由平滑肌细胞(SMC)收缩急性介导的。 SMC收缩性是通过细胞内钙浓度的增加([Ca2+] i)引发的,但是气道SMC中Ca2+信号的机制以及这些与气道口径变化的关系较少。 为了解决这个问题,我们开发了一种独特的肺切片制剂,该制剂保留了肺结构的许多特性,其中SMC的Ca2+信号传导以及相关的气道收缩或松弛可以通过共斑显微镜同时测量。 我们的数据表明,气道SMC显示了一系列基于IP3的CA2+信号范围,该信号由元素Ca2+信号,细胞内CA2+振荡和Ca2+波组成,并且这些信号与建立休息的呼吸道音调以及SMC和SMC和空中捕获的启动和维护。
因此,我们假设SMC中Ca2+信号的频率用于调节Ca2+气道口径。 要测试这个想法,我们计划确定:1)通过研究元素CA信号和自发CA2+振荡的机制和气道SMC的收缩的机制,负责CA2+建立静止气道音调的CA信号传导机制,2)小鼠模型的高反应性和哮喘。通过了解肺SMC中元素Ca2+信号传导和Ca2+振荡的分级机制,以及这些事件如何调节SMC收缩性并与气道口径相关,我们可以获得对调节气道高反应性调节治疗策略所需的必要见解。
项目成果
期刊论文数量(17)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
High-speed digital imaging of ependymal cilia in the murine brain.
- DOI:10.1016/s0091-679x(08)91013-x
- 发表时间:2009
- 期刊:
- 影响因子:0
- 作者:Lechtreck, Karl-Ferdinand;Sanderson, Michael J.;Witman, George B.
- 通讯作者:Witman, George B.
Ca(2+) oscillations regulate contraction of intrapulmonary smooth muscle cells.
- DOI:10.1007/978-1-60761-500-2_5
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:M. Sanderson;Y. Bai;J. Perez-Zoghbi
- 通讯作者:M. Sanderson;Y. Bai;J. Perez-Zoghbi
The frequency of calcium oscillations induced by 5-HT, ACH, and KCl determine the contraction of smooth muscle cells of intrapulmonary bronchioles.
- DOI:10.1085/jgp.200409216
- 发表时间:2005-06
- 期刊:
- 影响因子:3.8
- 作者:Perez, Jose F;Sanderson, Michael J
- 通讯作者:Sanderson, Michael J
Airway smooth muscle relaxation results from a reduction in the frequency of Ca2+ oscillations induced by a cAMP-mediated inhibition of the IP3 receptor.
- DOI:10.1186/1465-9921-7-34
- 发表时间:2006-02-23
- 期刊:
- 影响因子:5.8
- 作者:Bai, Y;Sanderson, MJ
- 通讯作者:Sanderson, MJ
Nitric oxide induces airway smooth muscle cell relaxation by decreasing the frequency of agonist-induced Ca2+ oscillations.
- DOI:10.1085/jgp.200910365
- 发表时间:2010-03
- 期刊:
- 影响因子:0
- 作者:Perez-Zoghbi JF;Bai Y;Sanderson MJ
- 通讯作者:Sanderson MJ
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MICHAEL J. SANDERSON其他文献
MICHAEL J. SANDERSON的其他文献
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{{ truncateString('MICHAEL J. SANDERSON', 18)}}的其他基金
Airway Hyper-responsiveness: from molecule to organ
气道高反应性:从分子到器官
- 批准号:
7474034 - 财政年份:2007
- 资助金额:
$ 30.15万 - 项目类别:
Airway Hyper-responsiveness: from molecule to organ
气道高反应性:从分子到器官
- 批准号:
7624173 - 财政年份:2007
- 资助金额:
$ 30.15万 - 项目类别:
Airway Hyper-responsiveness: from molecule to organ
气道高反应性:从分子到器官
- 批准号:
7291449 - 财政年份:2007
- 资助金额:
$ 30.15万 - 项目类别:
Calcium signaling in airway smooth muscle in lung slices
肺切片气道平滑肌中的钙信号传导
- 批准号:
6561385 - 财政年份:2003
- 资助金额:
$ 30.15万 - 项目类别:
Calcium signaling in airway smooth muscle in lung slices
肺切片气道平滑肌中的钙信号传导
- 批准号:
6734239 - 财政年份:2003
- 资助金额:
$ 30.15万 - 项目类别:
Calcium signaling in airway smooth muscle in lung slices
肺切片气道平滑肌中的钙信号传导
- 批准号:
7118660 - 财政年份:2003
- 资助金额:
$ 30.15万 - 项目类别:
Calcium signaling in airway smooth muscle in lung slices
肺切片气道平滑肌中的钙信号传导
- 批准号:
6938623 - 财政年份:2003
- 资助金额:
$ 30.15万 - 项目类别:
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