Ligand gaed ion channels配体门控离子通道.pptVIP

Ligand gated ion channels Channel structure Heteropentamer 4-transmembrane pass subunits Neurotransmitter diversity Post synaptic potentials Excitatory Inhibitory Modulation Structure Pentameric Charged pore Cation/anion selective 4-pass monomer Cytoplasmic basket Receptor activation 2-5 ligands per channel Ion selectivity Inactivation Neurotransmitters Transmitter Inotropic receptor Structure Acetylcholine Excitatory (nicotinic) Na/K channel Glutamate Excitatory Na/Ca/K NMDA/AMPA Serotonin Excitatory Na/K Glycine Inhibitory Cl- GABA g-Aminobutyric acid Inhibitory Cl- Transmitter Metabotropic receptor Acetylcholine Muscarinic receptor Glutamate Metabotropic glutamate Serotonin Serotonin receptor GABA b-type GABA Dopamine Dopamine receptor Norepinepherine Adrenergic receptor Acetylcholine, serotonin receptors Ach, Nicotinic AChR K+/Na+ permeable ~30 pS ? 17e6 Na+/s @ 90mV Broadly distributed, including striated muscle 5-HT3, 5-hydroxytryptamine Na+/K+ Esp raphne nuclei Attention/cognitive function Depression (SSRIs) Glutamate receptors NMDA (N-methyl-D-aspartate) Na+/K+/Ca2+ Mg2+ dependent voltage gating AMPA (amino-3—hydroxy-5-methyl-4isoxazolepropionic acid) Quisqualate Modest, 12 pS conductance Some are Ca2+ permeable; excitotoxicity Kainate Low, 4 pS conductance Inhibitory neurotransmitters Structurally similar to excitatory 5 subunit Dual-ligand binding Chloride conductance Adult: inhibitory Developmental: excitatory Higher intracellular Cl- K+/Cl- co-transporter Upregulated late in development Exports Cl- to establish ~-120mV equilibrium potential GABAA receptor g-Aminobutyric Acid Cl- channel, 18 pS, 20 ms Major inhibitory receptor in CNS Anesthetic target (barbiturates) Channel agonists Increase conductivity Addiction Reduced expression of calmodulin kinase Glycine receptor Relatively little receptor diversity 4 alpha subunits, 1 beta Strychnine binding 90 pS Retina, spinal motor, spinal pain Phosphorylation reduces conductivity Zinc nM-uM zinc potentia