1997 Fiscal Year Annual Research Report

膜2回貫通型カリウムチャネルの分子機能調節と生体機能異常

Research Project

Project/Area Number	07407006
Research Institution	Osaka University
Principal Investigator	倉智嘉久大阪大学, 医学部, 教授 (30142011)
Co-Investigator(Kenkyū-buntansha)	稲野辺厚大阪大学, 医学部, 助手 (00270851) 山田充彦大阪大学, 医学部, 助手 (10263237) 堀尾嘉幸大阪大学, 医学部, 助教授 (30181530)
Keywords	内向き整流K^+チャネル / 膜2回貫通型K^+チャネル / ATP感受性K^+チャネル / G蛋白質調節性K^+チャネル / スルフォニルユレア受容体 / アンカリング蛋白質
Research Abstract	本年度に本研究で得られた実績は以下のとおりである。 1.K_<ATP>チャネル関連:(1)血管平滑筋型K_<ATP>チャネルが、スルフォニールユレア受容体SUR2Bと2回膜貫通型K^+チャネルサブニットKir6.1の複合体として構成されることを、世界で初めて見いだした。またSUR2B/Kir6.1チャネルが、Kir6.2を含む心筋・膵臓型の古典的K_<ATP>チャネルとは全く異なる、細胞内ヌクレオチドによる調節、K^+チャネル開口薬による活性化を受けることを見いだした。(2)古典的K_<ATP>チャネルは細胞内ATP枯渇時に自然開口するが、血管平滑筋型K_<ATP>チャネルは自然開口しない。この機能的な差異の背景に存在する分子構造を、Kir6.1とKir6.2のキメラ蛋白質を用いて明らかにした。2.G蛋白質調節性K^+(K_G)チャネル関連:(1)黒質ドーパミンニューロンのK_Gチャネル分子が、GIRK2A、GIRK2C、PSD系列のアンカリング蛋白質の複合体として構成される可能性を見いだした。(2)下垂体前葉TSH分泌細胞で、GIRK1が分泌顆粒上に存在し、分泌に伴い細胞膜に移動して機能的なK_Gチャネルを構成する可能性を見いだした。3.その他の膜2回貫通型K^+チャネル関連:(1)PSD系列のアンカリング蛋白質が、網膜ミューラー細胞の内向き整流K^+チャネルK_<AB>-2と結合してチャネルのクラスタリングを起こし、また細胞膜上の機能的なK_<AB>-2チャネル数を増加させることを見いだした。(2)新しい膜2回貫通型K^+チャネルサブユニットの検索の過程で、心臓のcDNAライブラリーから新たな膜4回貫通型のK^+チャネルCTBAKをクローニングした。このチャネルは、心筋細胞の背景電流の構成に関与するらしく、細胞外pHで単一電流コンダクタンスの調節を受けることを見いだした。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Ito H.et al.: "Phosphorylation-independent inhibition by intracellular cyclic nucleotides of brain inwardly rectifying K^+ current expressed in Xenopus oocytes." FEBS Letters. 402. 12-16 (1997)
[Publications] Yamada M, et al.: "Sulfonylurea receptor 2B and Kir6.1 form a sulfonilurea-sensitive but ATP-insensitive K^+ channel." Journal of Physiology. 499. 715-720 (1997)
[Publications] Hirio Y, et al.: "Clustering and enhanced activity of an inwardly rectifying potassium channel,Kir4.1 by an anchoring protein. PSD-95/SAP 90 family." The Journal of Biological Chemistry. 272. 12885-12888 (1997)
[Publications] Hibino H, et al.: "An ATP-dependent inwardly rcctifying potassium channel,KAB-2(Kir4.1),in cochlear stria vascularis of inner ear : its specific subcellular localization and correlation with the formation of endocochlear potential." The Journal of Neuroscience. 17. 4711-4721 (1997)
[Publications] Morishige K, et al.: "Assignment of the murine inwardly rectifying potassium channel IRK3 gene (Kchj4) to the mouse Chromosome 15." Mammalian Genome. 8. 699-700 (1997)
[Publications] Takumi T, et al.: "A dye terminator method for automated DNA sequencing using four fluorescent dideoxynucleosides and thermal cycling." Analytical Sciences. 13. 735-739 (1997)
[Publications] Isomoto S.et al.: "Sur2 and Kcnj8 genes are tightly linked on the distal region of mouse chromosome." Mammalian Genome. 8. 790-791 (1997)
[Publications] Ishii M, et al.: "Expression and clustered distribution of an inwardly rectifying potassium channel,KAB-2/Kir4.1,on mam malian retinal muler cell membrane : Their Regulation by insulin and laminin signals." The Journal of Neuroscience. 17. 7725-7735 (1997)
[Publications] Tada Y, et al.: "Assignment of the glial inwardly rectifying potassium channel KAB-2/Kir4.1(Kcnj10) gene to the distal region of mouse chromosome 1." Genomics. 45. 629-630 (1997)
[Publications] Okuyama Y, et al.: "Properties of SUR2A/Kir6.2 ATP-sensitive K^+ channels expressed in a mammalian cell line,HEK 293T cells." Pfulers Archiv European Journal of Physiology. (in press). (1998)
[Publications] Kim DH, et al.: "Molecular cloning and functional expression of a novel weak inward rectifier K^+ channel with two pore domains predominantly expressed in heart." Circulation Research. (in press). (1998)
[Publications] Yakushigawa,H, et al.: "A novel junction-like membrane complex in the optic nerve astrocytes of the Japanese Macaqque with a possible relation to a potassium ion channel." Anatomical Record. (in press). (1998)

1997 Fiscal Year Annual Research Report

膜2回貫通型カリウムチャネルの分子機能調節と生体機能異常

Principal Investigator

倉智 嘉久 大阪大学, 医学部, 教授 (30142011)

Research Products

[Publications] Ito H.et al.: "Phosphorylation-independent inhibition by intracellular cyclic nucleotides of brain inwardly rectifying K^+ current expressed in Xenopus oocytes." FEBS Letters. 402. 12-16 (1997)

[Publications] Yamada M, et al.: "Sulfonylurea receptor 2B and Kir6.1 form a sulfonilurea-sensitive but ATP-insensitive K^+ channel." Journal of Physiology. 499. 715-720 (1997)

[Publications] Hirio Y, et al.: "Clustering and enhanced activity of an inwardly rectifying potassium channel,Kir4.1 by an anchoring protein. PSD-95/SAP 90 family." The Journal of Biological Chemistry. 272. 12885-12888 (1997)

[Publications] Hibino H, et al.: "An ATP-dependent inwardly rcctifying potassium channel,KAB-2(Kir4.1),in cochlear stria vascularis of inner ear : its specific subcellular localization and correlation with the formation of endocochlear potential." The Journal of Neuroscience. 17. 4711-4721 (1997)

[Publications] Morishige K, et al.: "Assignment of the murine inwardly rectifying potassium channel IRK3 gene (Kchj4) to the mouse Chromosome 15." Mammalian Genome. 8. 699-700 (1997)

[Publications] Takumi T, et al.: "A dye terminator method for automated DNA sequencing using four fluorescent dideoxynucleosides and thermal cycling." Analytical Sciences. 13. 735-739 (1997)

[Publications] Isomoto S.et al.: "Sur2 and Kcnj8 genes are tightly linked on the distal region of mouse chromosome." Mammalian Genome. 8. 790-791 (1997)

[Publications] Ishii M, et al.: "Expression and clustered distribution of an inwardly rectifying potassium channel,KAB-2/Kir4.1,on mam malian retinal muler cell membrane : Their Regulation by insulin and laminin signals." The Journal of Neuroscience. 17. 7725-7735 (1997)

[Publications] Tada Y, et al.: "Assignment of the glial inwardly rectifying potassium channel KAB-2/Kir4.1(Kcnj10) gene to the distal region of mouse chromosome 1." Genomics. 45. 629-630 (1997)

[Publications] Okuyama Y, et al.: "Properties of SUR2A/Kir6.2 ATP-sensitive K^+ channels expressed in a mammalian cell line,HEK 293T cells." Pfulers Archiv European Journal of Physiology. (in press). (1998)

[Publications] Kim DH, et al.: "Molecular cloning and functional expression of a novel weak inward rectifier K^+ channel with two pore domains predominantly expressed in heart." Circulation Research. (in press). (1998)

[Publications] Yakushigawa,H, et al.: "A novel junction-like membrane complex in the optic nerve astrocytes of the Japanese Macaqque with a possible relation to a potassium ion channel." Anatomical Record. (in press). (1998)

倉智嘉久大阪大学, 医学部, 教授 (30142011)