Its functional significance and molecular mechanism

其功能意义及分子机制

基本信息

批准号：
09044296
负责人：
KURACHI Yoshihisa
金额：
$ 7.68万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Activation of neuronal G protein-gated inwardly rectifying K+^+ (K_G) channels causes the formation of slow inhibitory postsynaptic potentials. Current opinion suggests that neuronal K_G channels are heterotetramers of Kir3.1 and Kir3.2, however there are several splicing variants of Kir3.1 and Kir3.2, and another subunit of Kir3.3 in the brain. Theoretically there might be so many diverse K_G channel assemblies composed of these subunits, however little knowledges are available for such diversification and physiological function of neuronal K_G channels. In substantia nigra (SN), K_G channel was an assembly of Kir3.2a and Kir3.2c. In this assembly, the former subunit is primarily responsible for formation of a functional K_G channel, and the latter controls subucellular localization of the K_G channel. Therefore, Kir3.2 splicing variants play distinct roles in the heteromeric assembly of the K_G channel in dopaminergic neurons of SN.When we studied about the distribution of K_G channels in the anterior pituitary lobe that we found K_G channel subunits Kir3.1 and Kir3.4 to be localized upon the membranes of intracellular dense core vesicles which contained TSH.TRH treatment provoked the translocation of these subunits to the plasma membrane and markedly enhanced K_G currents stimulated by dopamine and somatostatin. These data indicates a novel mechanism for the rapid insertion of functional ion channels into the plasma membrane, which could form a new type of negtive feedback control loop for hormone secretion in the endocrine system.

神经元G蛋白的激活向内门控的K+^+（K_G）通道的激活导致抑制性突触后潜能的形成。当前的意见表明，神经元K_G通道是Kir3.1和Kir3.2的异驱动器，但是Kir3.1和Kir3.2有几种剪接变体，而大脑中Kir3.3的另一个亚基。从理论上讲，可能有许多由这些亚基组成的不同的K_G通道组件，但是对于神经元K_G通道的这种多样化和生理功能，几乎没有知识。在黑质尼格拉（SN）中，K_G频道是Kir3.2a和Kir3.2c的组装。在此组件中，以前的亚基主要负责形成功能性K_G通道，后者控制K_G通道的亚核细胞定位。因此，kir3.2剪接变体在SN的多巴胺能神经元的杂体组装中起着不同的作用。当我们研究垂体前叶中K_G通道的分布时这些亚基易位到质膜，并显着增强了多巴胺和生长抑素刺激的K_G电流。这些数据表明了将功能离子通道快速插入到质膜中的新型机制，该机制可能形成一种新型的否定反馈控制回路，用于内分泌系统中的激素分泌。