Analysis of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function in adult heart using conditional transgenic mouse models
使用条件转基因小鼠模型分析成年心脏中超极化激活的环核苷酸门控(HCN)通道功能
基本信息
- 批准号:13327398
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Units
- 财政年份:2005
- 资助国家:德国
- 起止时间:2004-12-31 至 2011-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The sinoatrial node (SAN) is the physiological pacemaker of the heart and is predominantly responsible for autonomous heart beat generation. Heart rate control is achieved through control of SAN pacemaking by the autonomic nervous system, and sinus node dysfunction is a major cause for pacemaker implantation in humans. A major depolarizing current in SAN cells, If, has been proposed to act as the primary pacemaker under physiological conditions, but direct evidence for such a function is still missing, since loss-of-function mouse mutants lacking If die during embryonic stages of development. If is mediated by cAMP-binding HCN channels. To overcome the limitation of embryonic lethality in HCN knockout animals, we will use conditional transgenic mouse lines with functionally (dominant negative mutations) and reversibly (Tet-Off system) inactivated HCN pacemaker channels. With these mouse lines we plan to study the physiological and pathophysiological roles of HCN channels in cardiac pacemaking, autonomic control, conduction, contractility, and adaptation to increased workload in the adult heart.
窦房结是心脏的生理起搏器,主要负责自主心跳的产生。心率控制是通过自主神经系统控制窦房结起搏来实现的,而窦房结功能障碍是人类植入起搏器的主要原因。在生理条件下,SAN细胞中的一种主要的去极化电流IF被认为是主要的起搏器,但这种功能的直接证据仍然缺乏,因为缺乏功能缺失的小鼠突变体IF在胚胎发育阶段死亡。IF是由cAMP结合的HCN通道介导的。为了克服HCN基因敲除动物胚胎致死的局限性,我们将使用具有功能性(显性负突变)和可逆性(Tet-Off系统)灭活的HCN起搏通道的条件转基因小鼠系。利用这些小鼠系,我们计划研究HCN通道在成人心脏的心脏起搏、自主神经控制、传导、收缩和适应增加的负荷中的生理和病理生理学作用。
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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Professor Dr. Dirk Isbrandt其他文献
Professor Dr. Dirk Isbrandt的其他文献
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{{ truncateString('Professor Dr. Dirk Isbrandt', 18)}}的其他基金
Consequences of HCN/h pacemarker channel deficency for cortico-basal ganglia circuit function
HCN/h 起搏器通道缺陷对皮质基底节回路功能的影响
- 批准号:
257996791 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Clinical Research Units
High-resolution characterization of functional connectivity and behavior in healthy and transgenic mice from the neonatal period through adulthood
对健康转基因小鼠从新生儿期到成年期的功能连接和行为进行高分辨率表征
- 批准号:
239010391 - 财政年份:2013
- 资助金额:
-- - 项目类别:
Priority Programmes
Untersuchungen zur Pathophysiologie von Epilepsien des Neugeborenen- und Säuglingsalters in transgenen Mausmodellen
转基因小鼠模型新生儿和婴儿期癫痫病理生理学研究
- 批准号:
66045449 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Research Grants
Analyse von hippocampalen Oszillationen in KCNQ/M-Kanal-defizienten transgenen Mäusen
KCNQ/M通道缺陷转基因小鼠海马振荡分析
- 批准号:
37067352 - 财政年份:2007
- 资助金额:
-- - 项目类别:
Research Grants
Centralized data management and analysis facilities
集中数据管理和分析设施
- 批准号:
394775100 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Units
Transcriptomic and epigenetic profiles of basal ganglia-cortex networks in developmental epileptic encephalopathies
发育性癫痫脑病中基底节-皮质网络的转录组学和表观遗传学特征
- 批准号:
497785435 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
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