S1: Central Neurotransmitters Flashcards
What are autoreceptors?
They are pre-synaptic receptors which are involved with controlling release of NT
They are inhibitory
Explain synaptic transmission
- AP travels down axon and arrives at synaptic bouton
- When it reaches synapse, VGCCs open Ca2+ ions enter the presynaptic terminal
- The Ca2+ ions cause the synaptic vesicles to fuse with synaptic membrane
- NT are released into synapse
- NTs activate postsynaptic receptors or ion channels
- Some NTs diffuse out of the synapse, some are taken up by reuptake sites, some are metabolised
What do vesicles contain NT have in their membranes?
- Pump and Exchangers are found in the vesicle membrane that pump neurotransmitters from the cytosol where they are synthesised into the vesicle
- Calcium sensitive proteins on membrane of vesicle waiting for AP to arrive
What is clathrin?
Clathrin is a protein that reforms the vesicles and recycles the important proteins in the vesicle membrane by endocytosis
- It itself then dissociates from the vesicle and is reused
What are the 2 main types of synaptic receptors?
- Ionotropic
- Ligand gated ion channels
- Fast synaptic transmission - Metabotropic
- GPCR : G protein coupled receptors (mostly)
- Slow signal modulation
How is synaptic transmission terminated?
Neurotransmitter is removed.
This can be by:
- Diffusion (all NT)
- Enzymatic Breakdown
- Specific re-uptake sites
How are post synaptic potentials determined?
By adding up EPSPs and IPSPs
List some different types of NT
- Excitatory amino acids e.g. glutamate
- Inhibitory amino acids e.g. GABA and glycine
- Monoaminese.g. dopamine, NA, 5-HT
- Neuropeptides e.g. Substace P, CCK
What is the molecular weight of small and large CNS neurotransmitters?
Small (MW < 500)
Large (MW > 500)
Where are small NT synthesised?
Small molecular weight NTs are synthesised and stored in nerve terminals
Where are peptide NT synthesised (large)?
Peptide NTs are synthesised in neuronal cell bodies and transported down the axon to the nerve terminals.
Give examples of small CNS transmitters
- Ach
- Monoamines (NA, DA, 5-HT)
- Histamine
- AAs (Glutamic acid, aspartic acid, GABA, glycine)
- Nucleotides and nucleosides (adenosine, ATP)
Give examples of small CNS transmitters
- Hormones
- Opioid peptides
Give an example of an excitatory amino acid NT
Glutamate
How is glutamate synthesised?
Glutamine—->Glutamate
Phosphate activated glutaminase
Where is glutamate synthesised?
In nerve terminals
How is glutamate transported into vesicles?
VGLUT (vesicular glutamate transporters)
What receptors does glutamate act on?
Ionotropic receptors that are mainly found post synaptically
Metabotropic receptors (mGlu 1 - 8)
What are the 3 groups of mGlu receptors and where are they found?
How are they grouped?
Group 1: mglu 1,5 are found post-synaptically
Group 2: mglu 2,3 are found pre-synaptically
Group 3: mglu 4,6,7,8 are found pre-synaptically
Receptor types are grouped based on receptor structure and physiological activity
How is the synaptic transmission of glutamate terminated?
This is via EAAT
Excitatory amino acid transporter
What disorders is glutamate probably involved in?
Glutamate is probably involved in schizophrenia (NMDA receptor hypofunction) , epilepsy, after stroke (through neurotoxicity, causing apoptosis) and maybe some types of depression.
Give 2 examples of an inhibitory amino acid NT
GABA and Glycine
How is GABA synthesised?
It is synthesised from glutamate!
Glutamate ----> GABA Glutamate decarboxylase (GAD) and vitamin B6 (co-factor)
It is synthesised in nerve terminals
How is glycine synthesised?
Serine ——-> Glycine
Serine Hydroxymethyltransferase
Threonine ———>Glycine
Theronine Aldolase
It is synthesised in nerve terminals
