グルタミン酸による網膜双極性細胞におけるcGMP活性化された伝導性の抑制
Nature
|July 19, 1990
まとめ
グルタミン酸は,導電性を低下させることで網膜の脱極性双極性細胞 (DBCs) を高極化します. この反応には,光受容体の光伝導に似たGタンパク質媒介のプロセスがあり,周期的なGMP水解を増加させる.
科学分野:
- 神経科学は神経科学である.
- 網膜生理学 網膜生理学とは
- 分子シグナリング
背景:
- 網膜の脱極性双極性細胞 (DBCs) は,グルタミン酸によって独特にハイパーポラライズされています.
- グルタミン酸とAPBはDBC膜伝導性を低下させ,第2のメッセンジャーシステムが関与していることを示唆しています.
研究 の 目的:
- グルタミン酸がDBCに及ぼすハイパーポラライジング効果を媒介する第2のメッセンジャーシステムを明らかにする.
- DBCsにおけるグルタミン酸受容体活性化のメカニズムを調査する.
主な方法:
- 網膜のスライスで全細胞記録.
- グルタミン酸アナログ (APB) の応用と,サイクルGMP/GTPの細胞内応用.
- GTP-ガンマ-S,Gタンパク質阻害剤,およびフォスフォディエステラーゼ阻害剤の使用.
主要な成果:
- 細胞内サイクルGMPまたはGTPは,APBによって抑制された膜伝導性を活性化しました.
- APBは,GTP-gamma-S.による不可逆的な伝導性抑制を引き起こしました.
- Gタンパク質またはフォスフォディエステラーゼ阻害剤は,APB応答を低下させた.
結論:
- DBCグルタミン酸受容体は,Gタンパク質に依存する経路を通じて,周期的なGMP水解を増加させ,イオンチャネルを閉じる.
- このメカニズムは,光受容体におけるGタンパク質媒介の光伝導に非常に似ています.
関連する概念動画
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
G-Protein Gated Ion Channels
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Sensory organs,...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...


