9) Neurotransmitters and receptors

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Describe Chemical signalling by neurotransmitters
Transmitter is released into synaptic cleft -> diffuses and binds to receptor-> upon binding there are some informational changes to a receptor -> activation of a response
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What is excitation/ inhibition?
Excitation = firing of action potential/ movement of membrane potential over neuron towards firing. Inhibition = opposite
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How does A proton gradient drives vesicle filling
Vesicular proton pump uses energy of ATP to create the gradient of H+ and electric charge gradient Cationic transmitters such as monoamines and ACh depend on ΔpH whereas glutamate uses primarily the electrical component (ΔΨ).
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How can vesicle transporters be detected?
by e.g. immunostaining Also indicative of synapses, for places where neurotransmitters are stored and released
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How to indentify a neurotransmitter ?
Present in presynaptic terminal with: synthesis machinery & specialized vesicular transporter. Released upon presynaptic stimulation. When added to extracellular fluid should mimic effects of presynaptic stimulation.Mechanism for removal of a neurotr
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Describe Neurotransmitter synthesis
Occurs in the neuronal cell body & synapse.Specific to neuron types i.e. neurons of certain type are only able to make specific kinds of neurotransmitters-specialization.Neurons can change the neurotransmitters they synthesize=developmental switch
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Why do Transmitters have different speed of action?
Action of transmitter is determined by its receptor
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Temporal characteristics (speed and duration of action) of neurotransmitter depend on what?
kinetics of receptor: binding of ligand (transmitter), activation of receptor, desensitization of receptor
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What is desensitisation?
even at constant presence of transmitter, receptor is not active but stays transmitter-bound To be active again, receptor should be un-bound first
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Operating range of transmitter concentration depends on what?
affinity of the receptor, that is often described by the EC50 value higher EC50 means lower affinity transmitter is most efficient in concentrations ~ (0.1 ÷ 5)x EC50 receptor is saturated above (5 ÷ 10)xEC50
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Describe neurotransmitter receptors
transmembrane spanning proteins - some have an ion channel
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How are receptors held in place?
by scaffolding proteins: Receptors undergo dynamic bi-directional trafficking to the cell surface and back to the cytoplasm (internalisation by endocytosis)
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What are the different types of receptors?
Ionotropic: direct gating of channel by ligand Metabotropic: ion channel separate is from receptor receptor communicates to channel via intracellular messenger molecules ( G-proteins) G-Protein Coupled Receptors ( GPCRs)
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Ligand gated channels are made from what?
homologous building blocks which form an aqueous pore down their centre
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Key property of Metabotropic Receptors?
They are G protein Coupled (GTP-binding regulatory protein, a heterotrimer that disassembles when activated)
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Types of acetylcholine receptors?
nictoinic and muscarinic
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Structure of the nicotinic ACh receptor
Hetero-pentamer of four related subunits (αβγδ). Each subunit has a transmembrane α-helix (the M2 helix). The five M2 helices combine to form the pore. Each α-subunit contains an acetylcholine binding site. Binding of acetylcholine ‘opens’ the recep
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Opening of the nicotinic acetylcholine receptor?
bulky, hydrophobic Leu side chains of M2 helices close the channel->binding of 2 ACh molecules causes twisting of the M2 helices -> M2 helices now have smaller, polar residues lining the channel
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How does Nicotinic-acetylcholine receptor select ions ?
according to size and charge
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How/why do different tissues express variations of the ACH receptor?
Each subunit has diff genes (α-subunit may be encoded by 7 genes).Further diversity is achieved by RNA splicing.The different receptors can have different properties:Ligand binding characteristics, Channel conductance, Faster or slower kinetics,
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What are Muscarinic acetylcholine receptors?
GPCRs
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What are the gluatmate receptors>
AMPA, NMDA, metabotropic
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Role of serotonin neurones?
project to many areas of the brain-> Control of Appetite Sleep Mood Hallucinations Pain perception Vomiting
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What is dopamine?
Involved in reward and reinforcement Control of movement
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What is noradrenaline?
Wide spread activating system Affects sleep, attention and feeding behaviour
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Dopamine/noradrenaline Receptors?
ALL GPCRs (metabotropic) But many subtypes
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How does A proton gradient drives vesicle filling

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Card 4

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How can vesicle transporters be detected?

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Card 5

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How to indentify a neurotransmitter ?

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