Flashcards in 7 Neurotransmission Deck (31):
Q: Draw a simple diagram of a neuron and label. (5) Describe simple functions.
A: spine: receives inputs
soma: involved in integration of signals
axon: action potential is generated at the AXON HILLOCK
nerve ending/terminal: lots of mitochondria in the axon terminal because energy is needed to release neurotransmitter
Q: What has high resistance?
Q: How wide is the synaptic cleft? How long does it take for the action potential to get from one cell to the next?
A: about 20 - 100 nm wide
about 2 ms
Q: Describe the mechanism of neurotransmission. (6)
A: 1. Action potential comes along (wave of depolarisation) and the calcium channel gets activated
2. Calcium enters the nerve terminal and you get exocytosis of the neurotransmitter
3. It diffuses across the gap and interacts with the receptors
4. You have to get rid of the transmitter - this is done (for the amino acid transmitters) by TRANSPORTERS
5. These take the amino acids back into the terminal and other transporters take it back into the synaptic vesicles
6. You then use sodium-potassium pumps to bring it back to resting membrane potential
Q: What are the 3 stages of synaptic transmission?
A: 1. biosynthesis, packaging and release of neurotransmitter into synapse
2. receptor action
Q: What are the 3 classes of neurotransmitter? Give examples (3,2,1).
A: Amino Acids (e.g. glutamate= widespread use and is vital, GABA, glycine= localised to brain stem and spinal cord)
Amines (e.g. noradrenaline, dopamine)
Neuropeptides (e.g. opioid peptides)
Q: How do neurotransmitters vary? (2) What's the result of a neurone receiving multiple transmitter influences?
A: (There's a lot of diversity in the transmitters and their receptors)
-They may cause rapid or slow effects
-They vary in abundance from mM to nM CNS tissue concentration
integrated to produce diverse functional responses
Q: What are the essential components to synaptic transmission? (4)
A: -restricted to specialised structures=synapse
-fast within ms
-calcium is essential= transmitter release requires a local increase in intracellular Ca2+
-synaptic vesicles provide source of NT
Q: What does the activation of NT release require?
A: -calcium (dependant)
-rapid (electro mechanical) transduction (200us) = mu seconds =10^-6
Q: How can rapid release of NT occur? (3)
A: 1. synaptic vesicles are filled with NT and docked in the synaptic zone 'primed' (some are floating in the terminal region) = interaction between synaptic vesicle and synaptic membrane proteins allows rapid response
2. Ca2+ entry activates a Ca2+ sensor in the protein complex -> calcium sensor protein on the vesicle making the complex undergo conformational change
3. leads to membrane fusion of vesicles and NT release into the synaptic cleft
Q: Why is vesicle docking stable? (2)
A: tails are present on vesicular pre synaptic membrane which can cross over -> form super alphahelical coils
The net effect of this interaction is a stable complex of the vesicle at the synapse full of neurotransmitter
Q: What are synaptic vesicular proteins targets for?
Q: What effect does tetanus have on synaptic vesicular proteins? What is the effect that botulinum has? What can inhibit NT release?
A: SPASTIC paralysis
Zn2+ dependent endopeptidases
Q: What effect does alpha latrotoxin have on synaptic vesicular proteins? Explain.
A: (from the black widow spider)
Alpha latrotoxin binds to the protein at the site of release and prevents the vesicle closing down and recycling and the transmitter is released to complete depletion
Q: What is neurotransmitter action defined by? Describe. (2) Speed?
A: receptor kinetics
Ion Channel Receptor = FAST (msecs)
- mediate ALL fast excitatory and inhibitory transmission
G protein coupled receptor = slow (secs/mins)
-effectors may be enzymes (eg adenyl cyclase, phospholipase C, cGMP--PDE) or channels (Ca2+, K+)
Q: Give examples of ion channel receptors. (3)
-Gamma Amino Butyric Acid (GABA)
-Acetylcholine at nicotinic receptors
Q: Give examples of G-protein coupled receptors. (4)
A: CNS and PNS
-Acetylcholine at muscarinic receptors
-Neuropeptides (e.g. enkephalin)
Q: What is the difference between glutamate and GABA receptors? Glycine?
A: Glutamate = EXCITATORY - allows influx of SODIUM (cell is depolarised)
GABA = Inhibitory - allows influx of CHLORIDE (cell is hyperpolarised)
glycine= allows influx of CHLORIDE
Q: What are the main types of Glutamate Receptor? (2) Difference?
A: -AMPA receptor
respond to different configurations of glutamate and are encoded by different gene
Q: Describe AMPA receptors. (3) How does Ca2+ affect it?
A: -Responsible for the majority of FAST excitatory synapses
-Rapid onset, offset and desensitisation
modifies the AMPA receptor potentiating the AMPA receptor response and activates protein synthesis which modifies synapse formation
Q: Describe NMDA receptors. Speed? Inputs? (2) Ca2+?
A: Slow component of excitatory mechanism
Needs TWO INPUTS for this receptor to become activated = membrane needs to be depolarised AND the glutamate must bind -> serves as a coincidence receptor
This also lets in calcium
Q: What is glutamate formed from? How does it affect glutamate receptors?
A: Glutamate is formed from intermediary metabolism (e.g. glycolysis and the Krebs' cycle - it is formed from the transamination of alpha-ketoglutarate)
It interacts with the receptor and causes the entry of sodium and calcium through the NMDA receptor
Q: What happens once glutamate has fulfilled its role? Main? found on? (2)
A: Transporters on the pre-synaptic membrane and on glial cells causes the uptake of glutamate once it has fulfilled its role
The main transporter is EAAT2 (Excitatory Amino Acid Transporter 2) which is found on glial cells and on the pre-synaptic membrane
Once in glial cells or in the neurones, glutamate is then inactivated by glutamine synthetase to make glutamine (you simply add an amino acid onto the glutamate at it becomes inactivated)
Q: What does abnormal cell firing associated with excess glutamate in the synapse lead to?
Q: What is epilepsy? Caused by? Treatment? (3)
A: One of the commonest neurological diseases worldwide= characterised by recurrent seizures
Caused by abnormal release of glutamate leading to hyperexcitability of cells
treatment is focused on damping down excitatory activity by facilitating inhibitory transmission
-new generation of drugs targeting the GABA synapse have proved beneficial
-30% are refractory (resistant) to treatment
Q: What is the main inhibitory neurotransmitter?
Q: How are GABA and glutamate similar?
A: have very similar structures - removal of carboxyl group in glutamate gives you GABA
Q: What is GABA synthesised by? How does it act on GABA receptors?
A: Glutamic Acid Decarboxylase (GAD) - this is a Vitamin B6 enzyme
binds to the receptor and allows the entry of chloride which hyperpolarises the cell
Q: What happens once GABA has fulfilled its role?
A: There are transporters on Glial cells and on the presynaptic neurone which takes up GABA - these are GABA Transporters (GAT)
Once GABA has been taken up by the glial cell, it can be inactivated by an enzyme called GABA transaminase giving Succinate semialdehyde - this can feed into the TCA cycle
Q: What is the structure of the GABA receptor? Domains? What can be achieved by exploiting the GABA receptor? (4)
A: pentameric organisation
are pharmacologically important
produce anti-epileptics, sedatives and muscle relaxants, anxiolytic (anti anxiety)