1998 Fiscal Year Annual Research Report

神経細胞内における内向き整流K_+チャネルの部位特異的発現の機能的意義と分子機構

Research Project

Project/Area Number	09044296
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) 堀尾嘉幸大阪大学, 医学部, 助教授 (30181530) CLAPHAM Davi ハーバード大学, 医学部, 教授
Keywords	内向き整流カリウムチャネル / 膜2回貫通型カリウムチャネル / G蛋白質 / G蛋白調整性カリウムチャネル / アンカリング蛋白 / 中枢神経
Research Abstract	神経細胞では、G蛋白質制御内向き整流カリウム(K_G)チャネルの活性化により遅延性の抑制性シナプス後膜電位が形成される。K_Gチャネルを構成する分子は、Kir3.1-3.4の4種類が報告されており、特に中枢神経系ではKir3.4を除く3種の顕著な発現が認められる。K_Gチャネルの特徴は単一サブユニットのチャネル活性は低いのに対して、Kir3.1をKir3.2やKir3.4と共発現させると相乗的な活性を示すことである。現在、Kir3.1とKir3.2のへテロ複合体は、神経型K_Gチャネルと考えられているが、中枢神経系ではKir3.1、Kir3.2スプライシング変異体が複数種存在し、機能の未同定なKir3.3の発現も認められている。KGチャネルのへテロ複合体を形成する特性から、様々なサブユニットの組み合わせからなる多様なKGチャネルが理論上存在することになる。しかし、K_Gチャネルの多様性と神経細胞の生理機能との連関は未解決である。本研究により以下の点が明らかとなった。1)ラット黒質ドーパミン神経K_Gチャネルは同一遺伝子産物の2種のスプライシング変異体(Kir3.2a.Kir3.2c)からなるホモ複合体である。各々の変異体はKir3.2aはチャネル活性発現に、Kir3.2cは樹状突起シナプス局在化に機能する。そのため、両者が複合体を形成することは、生理的な機能チャネルの発現に合目的である。さらに、2)ラット下垂体TSH産生細胞では、Kir3.1とKir3.4が分泌顆粒上に局在する。この2つのサブユニットからなるKGチャネルはTRH刺激によるTSHの放出に伴い、分泌顆粒から細胞膜上に移行し、この細胞の抑制機構を増強する。このKGチャネルが関与するネガティブフィードバック機構はホルモン分泌調節において新規の生理機構である。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] A.Inanobe: "Characterization of G-Protein-Gated K_+ channels comopsed of Kir3.2 subnits in dopaminergi cneurons of the subsiantia nlgra" The Journal of Neuroscience. 19(3). 1006-1017 (1999)
[Publications] M.Yamada: "G protein regulation of potassium ion channels" Pharmacological Reviews. 50(4). 723-757 (1998)
[Publications] C.Kondo: "Chimerns of Kir6.1 and Kir6.2 reveal structural elements involved in spontaneous opening and unitary conductance of the ATP-sensitive K_+ channels" Receptors and Channels. 6. 129-140 (1998)
[Publications] E.Satoh: "Intracellular aucleotide-mediated gating of SUR/Kir6.0 complex potassium channels expressed in a mammalian cell line and its modification by pinacidil" Journal of Physiology. 511.3. 663-674 (1998)
[Publications] A.Fujita: "Assignment of mouse cardiac two-pore back ground K_+ channel Gene(KcnK4)to the proximal region of mouse chromosome 5" Genomics. 54. 183-184 (1998)
[Publications] T.Mouri: "Assignment of mouse inwardly rectifying potassium channel Kenj16 to the distal region of mouse charomosome 11" Genomics. 54. 181-182 (1998)
[Publications] Corey S.: "Identification of native atrial G-protein-regulated inwardly rectifying K_+(GIRK4)channel homomultimers." J.Biol.Chem.273. 27499-27504 (1998)
[Publications] Krapivinsky G.: "Gbeta binding to GIRK4 subunit is critical for G protein-gated K_+ channel activation." J.Biol.Chem.273. 16946-16952 (1998)
[Publications] Krapivinsky G.: "A novel inward rectifier K_+ channel with unique pore properties" Neuron. 20. 995-1005 (1998)
[Publications] Krapivinsky G.: "plCln binds to a mammalian homolog of a yeast protein involved in regulation of cell morphology." J.Biol.Chem.273. 10811-10814 (1998)
[Publications] Corey S.: "Number and stoichiometry of subunits in the native atrial g-protein-gated K_+ channel, IKACh." J.Biol.Chem.273. 5271-5278 (1998)
[Publications] Hambrock A: "Mg2_+ and ATP dependence of kATP channel moudiator binding to teh recombinant sulphonylurea receptor,SUR2B" British Journal of Pharmacology. 125. 577-583 (1998)
[Publications] T.Shindo: "SUR2 subtype(A and B)-dependent differential activation of the cloned ATP-sensitive K_+ channels by pinacidil and nicorandil" British Journal of Pharmacology. 124. 985-991 (1998)
[Publications] Y.Okuyama: "The effect of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K_+ channel expressed in a mammalian cell line, HEK293T cells" Pflugers Arch-Eur J.Physiol.435. 595-603 (1998)
[Publications] Y.Tada: "Inwardly rectifying K_+ channel in retinal Muller cells : Comparison with the KAB-2/Kir4.1 channel expressed in HEK293T cells" Japanese Journal of Physiology. 48. 71-80 (1998)
[Publications] D.Kim: "Cloning and functional expression of a novel cardiac two-pore background K_+ channel(cTBAK-1)" Circulation Research. 82. 513-518 (1998)

1998 Fiscal Year Annual Research Report

神経細胞内における内向き整流K_+チャネルの部位特異的発現の機能的意義と分子機構

Principal Investigator

倉智 嘉久 大阪大学, 医学部, 教授 (30142011)

Research Products

[Publications] A.Inanobe: "Characterization of G-Protein-Gated K_+ channels comopsed of Kir3.2 subnits in dopaminergi cneurons of the subsiantia nlgra" The Journal of Neuroscience. 19(3). 1006-1017 (1999)

[Publications] M.Yamada: "G protein regulation of potassium ion channels" Pharmacological Reviews. 50(4). 723-757 (1998)

[Publications] C.Kondo: "Chimerns of Kir6.1 and Kir6.2 reveal structural elements involved in spontaneous opening and unitary conductance of the ATP-sensitive K_+ channels" Receptors and Channels. 6. 129-140 (1998)

[Publications] E.Satoh: "Intracellular aucleotide-mediated gating of SUR/Kir6.0 complex potassium channels expressed in a mammalian cell line and its modification by pinacidil" Journal of Physiology. 511.3. 663-674 (1998)

[Publications] A.Fujita: "Assignment of mouse cardiac two-pore back ground K_+ channel Gene(KcnK4)to the proximal region of mouse chromosome 5" Genomics. 54. 183-184 (1998)

[Publications] T.Mouri: "Assignment of mouse inwardly rectifying potassium channel Kenj16 to the distal region of mouse charomosome 11" Genomics. 54. 181-182 (1998)

[Publications] Corey S.: "Identification of native atrial G-protein-regulated inwardly rectifying K_+(GIRK4)channel homomultimers." J.Biol.Chem.273. 27499-27504 (1998)

[Publications] Krapivinsky G.: "Gbeta binding to GIRK4 subunit is critical for G protein-gated K_+ channel activation." J.Biol.Chem.273. 16946-16952 (1998)

[Publications] Krapivinsky G.: "A novel inward rectifier K_+ channel with unique pore properties" Neuron. 20. 995-1005 (1998)

[Publications] Krapivinsky G.: "plCln binds to a mammalian homolog of a yeast protein involved in regulation of cell morphology." J.Biol.Chem.273. 10811-10814 (1998)

[Publications] Corey S.: "Number and stoichiometry of subunits in the native atrial g-protein-gated K_+ channel, IKACh." J.Biol.Chem.273. 5271-5278 (1998)

[Publications] Hambrock A: "Mg2_+ and ATP dependence of kATP channel moudiator binding to teh recombinant sulphonylurea receptor,SUR2B" British Journal of Pharmacology. 125. 577-583 (1998)

[Publications] T.Shindo: "SUR2 subtype(A and B)-dependent differential activation of the cloned ATP-sensitive K_+ channels by pinacidil and nicorandil" British Journal of Pharmacology. 124. 985-991 (1998)

[Publications] Y.Okuyama: "The effect of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K_+ channel expressed in a mammalian cell line, HEK293T cells" Pflugers Arch-Eur J.Physiol.435. 595-603 (1998)

[Publications] Y.Tada: "Inwardly rectifying K_+ channel in retinal Muller cells : Comparison with the KAB-2/Kir4.1 channel expressed in HEK293T cells" Japanese Journal of Physiology. 48. 71-80 (1998)

[Publications] D.Kim: "Cloning and functional expression of a novel cardiac two-pore background K_+ channel(cTBAK-1)" Circulation Research. 82. 513-518 (1998)

倉智嘉久大阪大学, 医学部, 教授 (30142011)