Lecture 4: Neurotransmitters and Pharmacology Flashcards
What does information transfer across the synapse require?
Release of neurotransmitters and interaction with postsynaptic receptors
What are key features of synaptic transmission?
- rapid timescale
- diversity
- adaptability
- plasticity
- learning and memory
What do the spines on dendrites do?
Increase surface area for more synaptic connections
How does the way the information is being transferred change?
The transmission is electrical in the pre-synaptic neurone before becoming chemical neurotransmission when it passes across the synapse and then it returns to electrical transmission in the post-synaptic neurone
What are the 3 stages of synaptic transmission?
- Biosynthesis, packaging and release of neurotransmitter
- Receptor action
- Inactivation
What can neurotransmitters be?
- amino acids (e.g. glutamate, GABA)
- amines (noradrenaline, dopamine)
- neuropeptides (e.g. opioid peptides)
What is the most important excitatory neurotransmitter?
glutamate
What is the most important inhibitory neurotransmitter?
GABA
Which inhibitory neurotransmitter is present in the spinal cord?
glycine
What is considered a rapid effect or slower effect?
Rapid = us - ms slower = secs
What does neurotransmitter release rely on?
increase in intracellular Ca2+ (200um) - this occurs by opening of Ca2+ ion channels
What in the presynaptic neurone provides the source of neurotransmitter?
synaptic vesicles
Outline the steps that lead to neurotransmitter release.
- membrane depolarisation
- Ca2+ channels open
- Ca2+ influx
- Vesicle fusion
- Vesicle exocytosis
- Transmitter release
What is the process called from the Ca2+ channels opening to transmitter release?
Electrochemical transduction
What are the synaptic vesicles?
Vesicles docked in the synaptic zone filled with neurotransmitter
What are the proteins on synaptic vesicles called and what are they important for?
Vesicular proteins - important in docking/fusion process and exocytosis
What are vesicular proteins the target of?
Neurotoxins
What do Zn2+ endopeptidases inhibit?
transmitter release
What does Tetanus toxin C tetani cause?
paralysis (breaks down skeletal muscle)
What does botulinum toxin C botulinum cause?
flaccid paralysis (muscles lose functionality)
What does alpha latrotoxin (from black widow spider) do?
Stimulates ACh release and cholinergic transmission to depletion
Outline transmitter release requirements.
- calcium dependent
- transmitter-containing vesicles to be docked on presynaptic membrane
- protein complex formation between vesicle, membrane and cytoplasmic proteins to enable both vesicle docking and a rapid response to Ca2+ entry leading to membrane fusion and exocytosis
- ATP and vesicle recycling (lots of mitochondria)
How is neurotransmitter action defined?
By receptor kinetics
What 2 receptors could a neurotransmitter bind to?
- ion channel receptor
- G protein coupled receptor
What do ion channel receptors mediate?
- Fast response (msecs)
- mediate all fast excitatory and inhibitory transmission
What do G-protein coupled receptors mediate?
- slow response (secs/mins)
- effectors may be enzymes (adenyl cyclase, phospholipase C or channels e.g. Ca2+, K+)
What are some examples of ion channel receptors?
CNS: glutamate, GABA Neuromuscular junction (NMJ): ACh at nicotinic receptors
What are some examples of G-protein coupled receptors?
CNS and PNS: ACh at muscarinic receptors, dopamine (DA), noradrenaline (NA), serotonin (5HT) and neuropeptides (e.g. enkephalin)
What are ion channel-linked receptors?
multiple subunit combinations-distinct functional properties
What are some types of ion channel-linked receptors?
- nicotinic cholinergic receptors (nAChR)
- glutamate (GluR)
- GABA (GABAR)
- Glycine (GlyR) receptors
What ion causes hyperpolarisation?
Cl- (makes resting potential even more negative so it’s harder to activate/propagate an action potential)
What is an EPSP?
excitatory postsynaptic potential (excitatory neurotransmitter receptor)
What is an IPSP?
inhibitory postsynaptic potential (inhibitory neurotransmitter receptor)
What are the 2 different glutamate receptors?
- AMPA receptor
- NMDA receptor
What is the AMPA receptor for?
- majority of fast excitatory synapses
- rapid onset, offset and desensitisation
- Na+ influx
What is the NMDA receptor for?
- slow component of excitatory transmission
- serve as coincidence detectors which underlie learning mechanisms
- Ca2+/Na+
Outline what occurs at an excitatory CNS synapse.
1) glutamate synthesised from glucose via TCA cycle and transamination
2) Glutamate reversibly binds post-synaptic receptors (linked to ion channels)
3) Rapid uptake of glutamate by excitatory amino acid transporters (EAATs)
4) Glutamate enzymatically modified by glutamine synthetase to glutamine in glial cell
What can lead to seizures?
abnormal cell firing with excess glutamate in the synapse
How can you measure electrical activity in the brain?
Electroencephalography
What is epilepsy characterised by?
recurrent seizures due to abnormal neuronal excitability
Outline what occurs at an inhibitory CNS synapse.
- GABA formed by decarboxylation of glutamate by glutamic acid decarboxylase (GAD)
- GABA reversibly binds post-synaptic receptors (Linked to ion channels)
- rapid uptake of GABA transporters (GATs)
- GABA enzymatically modified by GABA-transaminase to succinate semialdehyde in glial cell
Which drugs facilitate GABA transmission?
- antiepileptic
- anxiolytic
- sedative
- muscle relaxant
