Studies on physiological significance of hyperpolarization-activated cation channels

超极化激活阳离子通道的生理意义研究

基本信息

批准号：
15590185
负责人：
ISHII Takahiro
金额：
$ 2.3万
依托单位：
Graduate School of Medicine, Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590185/
关键词：
hyperpolarization channel Ih HCN homologous recombination tetracycline 相同組替相同組換え

项目摘要

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels contribute to physiological functions such as regulating cell excitability, eliciting rhythmic activities and so on. Four subtypes (HCN1-4) have ever been identified. We previously cloned HCN4, which shows the slowest activation kinetics and the profound modulation by cAMP. To investigate the physiological roles of HCN4, we have generated a transgenic (Tg) mouse, in which tetracycline repressor protein (TetR) is expressed under the control of HCN4 promoter. This mouse was crossbred with another Tg mouse, in which GFP expression is regulated by TetR. Thus, generated Tg mouse expressed GFP in HCN4-expressing cells. We observed on this Tg mouse revealed that GFP fluorescence and HCN4 immunoreactivity (HCN4-IR) were colocalized in the cerebrum, the sino-atrial node, the taste buds and the retina, all of which were previously confirmed to express HCN4. The olfactory receptor neurons (ORN) expressed GFP, where only HCN current (Ih) had been formerly reported, however, its physiological roles remain unknown. HCN4-IR was detected in the olfactory knobs, the soma and the axon bundles of the ORN. We also found that HCN2 was expressed in the axon bundles of the ORN. Electrophysiological studies are in progress to analyze the physiological properties of HCN channels in the ORN.

超极化激活的循环核苷酸门控（HCN）通道有助于生理功能，例如调节细胞兴奋性，引起节奏活动等。已经确定了四个亚型（HCN1-4）。我们以前克隆了HCN4，它显示了最慢的激活动力学和cAMP的深刻调节。为了研究HCN4的生理作用，我们产生了一种转基因（TG）小鼠，其中四环素抑制剂蛋白（TERT）在HCN4启动子的控制下表达。该小鼠与另一种TG小鼠杂交，其中GFP表达受TER调节。因此，产生的TG小鼠在表达HCN4的细胞中表达GFP。我们在这款TG小鼠上观察到了GFP荧光和HCN4免疫反应性（HCN4-IR）在大脑，中央淋巴结，味蕾和视网膜中共定位，所有这些先前已证实所有这些。嗅觉受体神经元（ORN）表达GFP，但以前仅报道了HCN电流（IH），但其生理作用仍然未知。在ORN的嗅觉旋钮，SOMA和轴突束中检测到HCN4-IR。我们还发现HCN2在ORN的轴突束中表达。正在进行电生理研究，以分析ORN中HCN通道的生理特性。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Halothane Inhibits an Intermediate Conductance Ca^<2+>-activated K+ Channel by Acting at the Extracellular Side of Ionic Pore

氟烷通过作用于离子孔的细胞外侧抑制中间电导 Ca^<2>-激活的 K 通道

DOI：
发表时间：
2003
期刊：
Anesthesiology 99
影响因子：
0
作者：
Mitsuko Hashiguchi-Ikeda;Tsunehisa Namba;Takahiro M.Ishii;Taizo Hisano;Kazuhirko Fukuda
通讯作者：
Kazuhirko Fukuda

「研究成果報告書概要(欧文)」より

摘自《研究结果报告摘要（欧洲）》