Neurotransmitters Flashcards
what are some properties of synaptic transmission?
- Rapid timescale:
- diversity
- adaptability
- plasticity: synapse changes with experience
- learning and memory
Features of a neurone
- Spine are protrusions from dendrites (information receptor)
- Soma: cell body. All the integration. Can modify all the integration
- axon: transmits action potential to the nerve terminal. Communication between cells-neurotransmitter release.
Where does integration of the signals coming down the dendrites occur?
In the soma
What is the width of a synaptic cleft?
20-100nm wide
Where is the action potential generated?
Axon hillock
Why are there lots of mitochondria in the axon terminal?
Energy is required to release neurotransmitter
Describe the process of neurotransmission
- Action potential comes along
- Activates calcium channels
- Calcium enters the nerve terminal
- Exocytosis of the neurotransmitter contained in the vesicle
- Diffuses across the synaptic cleft and binds to receptors on the postsynaptic neuron
How is a neurotransmitter removed from the synaptic cleft?
- This is done by transporters (for amino acid transmitters)
- These take amino acids back into the terminal
- Other transporters take it back into the synaptic cleft
What are the three classes of neurotransmitter? Give examples.
- Amino Acids e.g. glutamate, GABA, glycine
- Amines e.g. noradrenaline, dopamine
- Neuropeptides e.g. opioid peptides
What is the main inhibitory and excitatory neurotransmitter in the CNS
Excitatory- Glutamate
inhibitory- GABA
Describe the process of synaptic transmission.
The vesicles dock on the pre-synaptic membrane and await a signal before the contents of the vesicles are expelled into the synaptic cleft.
Where are the vesicles present in the presynaptic synapse?
- Some vesicles are docked in the active zone at the site of the synapse
- Others are floating in the terminal region
How are the vesicles docked stably?
- There is an interaction between the presynaptic membrane and the vesicle proteins which allows the vesicles to be docked stably
- Interaction allows a rapid response
- There are alpha-helical structure which interact together to form a super helix
- Net effect of this interaction = stable complex of the vesicle at the synapse full of neurotransmitter
What drives the release of the neurotransmitter into the synaptic cleft?
- Vesicle requires a signal for release and the signal is calcium
- High concentration of calcium channels at the sites of docking of the vesicles
- Calcium enters through these channels
- Causes a calcium dependent change in a calcium sensor protein on the vesicle
- Causes conformational change in the complex
- Drives release of neurotransmitter
State three toxins that target synaptic vesicle proteins and the effects that they have
Tetanus
- causes spastic paralysis
- has zinc-dependent endopeptidases that inhibit transmitter release
Botulinum
- causes flaccid paralysis
Alpha-latrotoxin (from black widow spider)
- prevents recycling of the vesicles and hence releases the transmitter to total depletion
What is required for transmitter release?
Docking - transmitter filled vesicles must be docked on the presynaptic membrane
Protein complex formation - between vesicle, membrane and cytoplasmic proteins - this allows vesicle docking and a rapid response to calcium entering the axon terminal
ATP and vesicle recycling
What are the two types of receptor and what is the most important difference in their properties?
- Ion channel receptor
- Fast (milli seconds) - G-protein coupled receptors
- Slow (sec/min)
What are examples of Ion channel receptors?
CNS
- Glutamate
- Gamma Amino Butyric Acid (GABA)
Neuromuscular Junction
- Acetylcholine at nicotinic receptors
What are examples of G-protein coupled receptors?
CNS and PNS
- Acetylcholine at muscarinic receptors
- Dopamine
- Noradrenaline
- 5-hydroxytryptamine
- Neuropeptides (e.g. enkephalin)
What is the effect of glutamate on the postsynaptic membrane?What is the effect of GABA on the postsynaptic membrane?
Glutamate is excitatory - causes influx of Na+
GABA in inhibitory - causes influx of Cl-
What are the two main types of glutamate receptors and their properties?
- AMPA Receptors
- Responsible for the majority of FAST excitatory synapses
- Rapid-acting
- Rapid onset, offset and desensitization - NMDA Receptors
- Slower acting (despite still being excitatory and fast)
- Requires two conditions for activation: - Depolarisation of membrane
- Glutamate must bind
- Lets in Ca2+
Where is glutamate formed?
Glutamate is a product of intermediary metabolism (e.g. glycolysis and TCA cycle)
- Formed from the transamination of alpha-ketoglutarate
How is an excitatory synapse mediated by glutamate?
- Interacted with the receptor and causes entry of sodium and calcium through the NMDA receptor
- Transporters on the presynaptic membrane and on glial cells causes the uptake of glutamate once it has fulfilled its role
What is the main transporter of glutamate and where is it found?
- Main transporter is EAAT2 (Excitatory Amino Acid Transporter 2)
- Found on glial cells and on the presynaptic membrane
