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Chapter6 Ligand-gated Channels of Fast Chemical Synapses

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Presentation on theme: "Chapter6 Ligand-gated Channels of Fast Chemical Synapses"— Presentation transcript:

1 Chapter6 Ligand-gated Channels of Fast Chemical Synapses
Receptor-operated channels ①Ligand-gated channel (ionotropic) → fast chemical synapse ②Metabotropic channel → slow cell signal Ligand-gated channel Metabotropic channel

2 Ligand-gated channels
Metabotropic channels Ligand-gated channels nAchR NMDAR, AMPA & KAR GABAAR P2X 5-HT3 Metabotropic channels GIRK ATP-sensitive K channel (Ik,ATP) CNG channel(cyclic nucleotide-gated ch.) BK channel (Ca2+ activated K+ channel) ANO1 (Ca2+ activated Cl- channel) Some TRP channels

3 Ligand-gated channels
nAchR, GABAA-R, Glycine R, 5-HT3R Pentamer AMPA-R, NMDA-R, KA-R Tetramer P2X channels

4 nAchR cloning strategy (Shoshaku Numa, Kyoto U)
The first of ①Patch clamped Neher& Sakmann 1973 (1996; 노벨상) ② Purified ③ Sequenced ④ Cloned ⑤ Reconstitution in lipid bilayer ⑥ Heterologous Expression nAchR cloning strategy (Shoshaku Numa, Kyoto U) Structural homology of Torpedo californica acetylcholine receptor subunits Noda et al., Nature (1983a, b, c). Electric ray; rich in nAchR Purified a-bungarotoxin-bound protein Sequencing the N-terminal peptide Synthesis of oligo nucleotide (degenerate) Fishing out mRNAs of nAchR by hybridization

5 nAchR: Fast transmission in neuromuscular junction
End plate potential or current: inactivation

6 Miniature End Plate Potential (MEPP)
Poison Distribution: quantal releas NMDAR & AMPAR NMDAR; Ca2+-permeable AMPAR; Ca2+-impermeable most of fast synaptic transmission: AMPAR NMDAR. ∵ Mg2+ block → voltage dependent cf. Glutamate; major excitatory NT Once depolarized → Removal of Mg2+ block → NMDA-R activation → Na+, Ca2+ influx → synaptic plasticity such as Long term potentiation (LTP)or LTD Priming effect: Molecular basis of Learning & Memory

7

8 GABAaR Sedatives Anesthetics

9

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