8. Neurotransmitters Flashcards
5 key features for effective synaptic transmission
Rapid timescale Diversity Adaptability Plasticity Learning and memory
Where is the signal received?
At dendritic spines
Where does integration of the signals coming down the dendrites occur?
Soma
What is the width of a synaptic cleft? What does this represent and what is the consequence of this?
20-100 nm
Represents high resistance to transfer of electrical charge
This is why chemical transmission is required
Why are there many mitochondria in the presynaptic nerve terminal?
Neurotransmission is a highly energy dependent process
3 steps of synaptic transmission
- Biosynthesis, packaging and release of neurotransmitter
- Receptor action
- Inactivation
What are the 3 classes of neurotransmitter? Give an example of each
Amino acids e.g. gamma amino butyric acid (GABA)
Amines e.g. noradrenaline
Neuropeptides e.g. Opioid peptides
Diversity of neurotransmitters
May mediate rapid (μs - ms) or slower effects (ms)
Vary in abundance from mM to nM CNS tissue concentrations
Which type of neurotransmitter is most prevalent in the CNS? Give 2 examples
Amino acid neurotransmitters
Glutamate: key excitatory transmitter
GABA: Key inhibitory transmitter
Describe the activation of a CNS synapse
AP depolarises cell, causes Na+ influx
AP triggers Ca2+ entry required for neurotransmitter release
Neurotransmitter vesicle fuses with membrane
Neurotransmitter is released by exocytosis
Neurotransmitter acts on receptor
Neurotransmitter removed to stop action on synapse by transporter
What are the 4 essential components to synaptic transmission?
Restricted to specialised structures: the SYNAPSE Fast ~ within ms (200 μs) Calcium: transmitter release requires an increase in intracellular Ca2+ (200 μM) Synaptic vesicles (SVs) provide the source of neurotransmitter
How can rapid release occur?
Synaptic vesicles filled with neurotransmitter and docked in the synaptic zone, strong association with proteins, form a complex “primed”: ready for action
Ca2+ entry activates a Ca2+ sensor in the protein-vesicle complex, changing conformation: promotes fusion with membrane and opening of a pore to release transmitter
Interaction between synaptic vesicle and synaptic membrane proteins allows rapid response
List 3 neurotoxins that target vesicular proteins
Tetanus toxin: Paralysis (zinc dependent endopeptidases inhibit transmitter release)
Botulinum toxin: Flaccid paralysis
Alpha Latrotoxin: prevents recycling of the vesicles and hence releases the transmitter to total depletion
What does transmitter release require?
Transmitter containing vesicles to be docked on the 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
What are the 2 types of receptor and what is the most important difference in their properties?
Ion Channel Receptor: FAST (u-msec)
G-protein linked receptor: SLOW (s-minutes)
What may the effectors of G-protein linked receptors be?
Enzymes or channels
What is the effect of glutamate on the post-synaptic membrane?
Glutamate is excitatory: causes influx of Na+
What is the effect of GABA on the post-synaptic membrane?
GABA is inhibitory: causes influx of Cl-
What are the 2 main types of glutamate receptor? State some properties.
AMPA: rapid acting: causes depolarisation, only operates on cell that’s already been depolarised, majority of fast excitatory synapses, rapid onset, offset and desensitisation
NMDA: slower acting (despite still being excitatory and fast), serve as coincidence detectors which underlie learning mechanism, requires 2 conditions for activation = depolarisation of membrane + glutamate binding, NMDA lets in Na+ and Ca2+
Where is glutamate formed?
Glutamate is a product of intermediary metabolism
e.g. glycolysis and TCA cycle
Which transporter actively takes glutamate up into glial cells on the pre-synaptic membrane?
Excitatory Amino Acid Transporter (EAAT)
How is glutamate inactivated in the glial cells?
Glutamate is converted to glutamine by GLUTAMINE SYNTHETASE
What causes epileptic seizures?
Increased release of glutamate, causing hyperexcitability
What is epilepsy characterised by?
Recurrent seizures due to abnormal neuronal excitability
