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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.

超极化激活的环核苷酸门控（HCN）通道具有调节细胞兴奋性、引发节律性活动等生理功能。目前已鉴定出四种亚型（HCN1-4）。我们先前克隆的HCN4显示出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，我们构建了四环素抑制蛋白（TetR）在HCN4启动子控制下表达的转基因（Tg）小鼠。该小鼠与另一只Tg小鼠杂交，其中GFP表达受TetR调节。因此，生成的Tg小鼠在表达hcn4的细胞中表达GFP。我们在这只Tg小鼠上观察发现，GFP荧光和HCN4免疫反应性（HCN4- ir）共定位于大脑、窦房结、味蕾和视网膜，这些都是先前证实表达HCN4的部位。嗅觉受体神经元（ORN）表达GFP，此前仅报道过HCN电流（Ih），但其生理作用尚不清楚。在ORN的嗅觉旋钮、体细胞和轴突束中检测到HCN4-IR。我们还发现HCN2在ORN的轴突束中表达。电生理研究正在进行中，以分析在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）

A novel Ca2+ indicator protein using FRET and calpain-sensitive linker.

DOI：
10.1016/j.bbrc.2005.08.089
发表时间：
2005-10
期刊：
Biochemical and biophysical research communications
影响因子：
3.1
作者：
Kenji Takatsuka;T. Ishii;H. Ohmori
通讯作者：
Kenji Takatsuka;T. Ishii;H. Ohmori

「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）》

DOI：
发表时间：
2006
期刊：
Seibutsu Butsuri 46(1)
影响因子：
0
作者：
Yasushi Shigeri;Keiko Shimamoto
通讯作者：
Keiko Shimamoto

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

Hyperpolarization-activated cyclicnucleotide gated cation channels regulate auditory coincidence detection in nucleus laminaris of the chick.

超极化激活的环核苷酸门控阳离子通道调节雏鸡层状核中的听觉重合检测。