Lecture 4 - Post synaptic events in synaptic transmission Flashcards
What are the two types of receptor that neurotransmitter released by the pre syaptic nerve terminal can interact with?
- ionotropic/ligand gated ion channels
- metabotropic/G-protein coupled receptors
What are the features of ionotropic and metabotropic receptors?
Ionotropic -fast -mediate changes in membrane protential Metabotropic -slow -can influence channel activity via second messengers (e.g. Ca2+, IP1, cAMP)
What did Nigel Unwin elucidate?
The first neurotransmitter receptor structure using cryo-EM
What does EPSP and IPSP stand for?
EPSP: excitatory post synaptic potential
IPSP: inhibitory “”””””””””””””””””””””””””””””””
What channel mediates depolarisation in the post synaptic nerve? (creates an EPSP)
Influx of sodium ions through a sodium channel
What channel mediates hyperpolarisation in the post synaptic nerve? (creates an IPSP)?
Influx of chloride ions through a chloride channel
What are the two different types of receptor in the post synaptic nerve terminal?
Ligand-gated ion channel (Ionotropic)
G protein coupled receptors (Metabotropic)
How does neurotransmitter release mediate the function of Ionotropic receptors in the post synaptic nerve terminal?
Neurotransmitter binds to extra polypeptides on the outside of the cell causing a conformational change in the channel causing it to open
-ions diffuse in along concentration gradient
How does neurotransmitter release mediate the function of Metabotropic receptors in the post synaptic nerve terminal?
- when the neurotransmitter binds to the receptor on the membrane it causes a conformational change leading to the activation of a protein complex coupled to the receptor in the intracellular side of the membrane (G-Protein)
- G protein unit bound to GTP moves along the intracellular membrane and can activate other intracellular signalling pathways e.g. the indirect opening of other ion channels to regulate the action potential (slow)
Where are Neurotransmitter receptors located and why?
- post synaptic membrane to generate an action potential
- presynaptic membrane to modulate neurotransmitter release
How did Nigel Unwin elucidate the Acetycholine receptor?
As membrane protein cannot easily be crystallised (need lipids surrounding)
- found tissue with a lot of Acetylcholine receptors (torpedo ray) snd imaged the tissue by electron microscopy
- as there were lots of receptors on the membrane he could average their structure and activity
What is the structure of the acetylcholine receptor?
5 subunits: -2α (ligand binding site) -β -γ -δ 4 transmembrane spanning domains
What is the function of the acetylcholine receptor at the skeletal muscle neuromuscular junction?
mediates muscle contraction
What is the function of the acetylcholine receptor in the CNS?
important in the prefrontal cortex in regulating transmission
What is the process of acetylcholine binding to its receptor?
- ACh molecules bind to the α subunits causing the receptor to undergo a conformational change
- the channel opens to allow cations to pass through (i.e. Na+/K+) due to the large pore size
What are the ionotropic and metabotropic receptors for ACh?
Ionotropic
-nicotinic acetycholine receptor (nAChR)
Metabotropic
-muscarinic acetycholine receptor
What are the Ionotropic glutamate receptors divided into?
- non NMDA receptors, AMPA & kainate
- NMDA receptor
What are the agonists for the AMPA receptor & the kainate ionotropic glutamate receptor, and what do they gate?
AMPA receptor: Alpha-amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid (AMPA) Kainate receptor: Kianic acid
Gate Na+/K+
How do the non-NMDA ionotropic glutamate receptors cause a fast EPSP?
via an increase in conductance to monovalent cations (Na+ and K+)1
What is the agonist for the NMDA receptor and what does ti gate/dependent on?
agonist:
NMDA (N-Methyl-D-Aspartate)
Ca2+ dependent, preference for gating Ca2+ (can act as a second messenger) but can gate other ions
When does the NMDA ionotropic glutamate receptor open?
in the presence of glutamate
-during depolarisation of the postsynaptic neuron
What are the kinetics of the NMDA and AMPA dependent EPSCs, and how have these been observed?
When glutamate is added
-EPSC spike and decay very fast up to around 50pA
(due to the very quick opening and closing of the AMPA receptor)
-EPSC increase and decrease (to around 25pA) very slowly
(due to the slow opening and closing of NMDA receptor, slow decay potentially also to do with signalling events e.g. activated by calcium influx)
Observe
Can observe the AMPA mediated ESPC without the NMDA mediated EPSC when in the presence of NMDAR agonists
And the same for NMDA receptors
What is the structure of SPINEs and where are they found?
- spine tail (connect to dendrite)
- spine head (containing the presynatpic density)
What do SPINEs function as?
-post synapses, contain AMPA and NMDA receptors
