Molecular dissection of inwardly rectifying KィイD1+ィエD1 channel, Kir4.1/KィイD2abィエD2-2, of glial cells.

神经胶质细胞内向整流 KiD1+D1 通道 Kir4.1/KD2abD2-2 的分子解剖。

• 批准号: 10470023
• 负责人: HORIO Yoshiyuki
• 金额: $ 8.32万
• 依托单位: Sapporo Medical University (1999)Osaka University (1998)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470023/
• 关键词: potassium; channel; glia; water channel; retina; cochlea; stomach; gastric acid; 内向き整流性カリウムチャネル; カリウム; PDZドメイン; 壁細胞; グリア細胞; バリウム; 胃酸

(3) Kir4.1 was expressed in satellite cells of cochlea ganglia. Because Kir4.1 prominently localized in myelin sheaths of satellite cells, Kir4.1 may participate in KィイD1+ィエD1 spatial buffering action of cochlea ganglia.We found that inwardly rectifying potassium channel, Kir4.1/KィイD2abィエD2-2, was expressed in glial cell. To investigate further the distribution and function of Kir4.1, we examined various tissues and obtained following results.(1) Using immunoelectron microscopic technique, we found that Kir4.1 co-localized with water channel, AQP4, in the membranes of retinal Muller glial cells adjacent to basal membranes. Previously, water transport has been considered to couple KィイD1+ィエD1 transport. Thus, Kir401 and AQP4 may regulate water content of neural tissues.(2) Kir4.1 was found in retinal pigment epithelial cells, suggesting Kir4.1 participates in extracellular KィイD1+ィエD1 homeostasis of rod outer segments.(4) Kir4.1 was expressed in gastric parietal cells. BaィイD12+aィエD1, an inhibitor of inwardly rectifying KィイD1+ィエD1 channel, suppressed acid secretion of isolated rat parietal cells, but inhibitors of voltage sensitive and CaィイD12+ィエD1-activated KィイD1+ィエD1 channels did not. Immunoelectron microscopic examination indicated that Kir4.1 localized in apical membranes but not in tubulovesicles and basolateral membranes of parietal cells. These results indicated that Kir4.1 may participate in acid secretion of stomach. Kir4.1 may export KィイD1+ィエD1 ions into gastric lumen which are imported into parietal cells by HィイD1+ィエD1. KィイD1+ィエD1-ATPase.

(3)Kir4.1在耳蜗神经节的卫星细胞中表达。由于Kir4.1主要定位于卫星细胞的髓鞘中，因此Kir4.1可能参与了耳蜗神经节的钾离子通道（K + D1）+钾离子通道（K + D1）的空间缓冲作用。为了进一步研究Kir4.1的分布和功能，我们检查了各种组织，并获得了以下结果。(1)利用免疫电镜技术，我们发现Kir4.1与水通道（AQP 4）共定位于视网膜Muller胶质细胞基底膜附近的膜上。以前，水的运输被认为是耦合K D1+ K D1的运输。因此，Kir 401和AQP 4可能调节神经组织的含水量。(2)Kir4.1在视网膜色素上皮细胞中表达，提示Kir4.1参与了视杆细胞外段细胞外K + D1+ D1的动态平衡。(4)Kir4.1主要表达于胃壁细胞。内向整流钾通道抑制剂Ba ~（2+）D_1 + Ca ~（2+）D_1抑制离体大鼠壁细胞的酸分泌，但电压敏感性钾通道抑制剂和Ca ~（2+）D_1 + Ca ~（2+）D_1激活的钾通道抑制剂则无此作用。免疫电镜观察显示Kir4.1定位于壁细胞顶膜，而不定位于壁细胞小管囊泡和基底外侧膜。这些结果表明Kir4.1可能参与胃酸分泌。Kir4.1可将K + D1+ K2 + D1离子输出到胃腔，而K + D1+ K2 + D1离子则通过H + D1+ K2 + D1输入壁细胞。KイD1+ D1-ATP酶。

项目成果

Repunte VP et al.: "Extracellular links in Kir subunits control the unitary conductance of SUR/Kir6.0 ion channels"EMBO J.. 18. 3317-3324 (1999)

Repunte VP 等人：“Kir 亚基中的细胞外连接控制 SUR/Kir6.0 离子通道的单一电导”EMBO J.. 18. 3317-3324 (1999)

Horio Y. et al.: "Current Topics in Membranes. Vol46, Potassium Channels : Molecular Structure, Function, and Diseases"Academic press. 492 (1999)

Horio Y.等人：“膜的当前主题。第46卷，钾通道：分子结构、功能和疾病”学术出版社。

HAMBROCK,A., LOFLER-WALZ,C., KLOOR,D., DELABAR,U., HORIO,Y., KURACHI,Y. QUAST,U.: "KATP channel modulator binding to sulfonylurea receptors SUR2A and SUR2B: Opposite effects of MgADP."Mol. Pharmacol. 55. 832-840 (1999)

HAMBROCK,A.、LOFLER-WALZ,C.、KLOOR,D.、DELABAR,U.、HORIO,Y.、KURACHI,Y.

MOURI,T., KITTAKA,N., HORIO,Y., COPELAND,NG., JENKINS,NA., KURACHI,Y.: "Assignment of mouse inwardly rectifying potassium channel Kcnj16 to the distal region of mouse chromosome 11."Genomics. 54. 181-182 (1998)

MOURI,T.、KITTAKA,N.、HORIO,Y.、COPELAND,NG.、JENKINS,NA.、KURACHI,Y.：“将小鼠内向整流钾通道 Kcnj16 分配到小鼠 11 号染色体的远端区域。”基因组学

Inanobe A et al.: "Splicing variants of Kir3.2 are assembled but play distinct functional roles in the G protein-gated K+ channel of the substantia nigra." J.Neurosci.19. 1006-1017 (1998)

Inanobe A 等人：“Kir3.2 的剪接变体被组装起来，但在黑质的 G 蛋白门控 K 通道中发挥着独特的功能作用。”