5- neurotransmitters Flashcards Preview

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Flashcards in 5- neurotransmitters Deck (10):

What are the 3 classes of neurotransmitter

Amino Acids (e.g. glutamate, GABA, glycine) Amines (e.g. noradrenaline, dopamine) Neuropeptides (e.g. opioid peptides)
• They may cause rapid or slow effects
• They vary in abundance from mM to nM


Describe the rapid release of neurotransmitter

There are a large number of protein in the axon terminal
• Some vesicles are docked in the active zone at the site of the synapse
• Other vesicles are floating in the terminal region
• There is an interaction between the presynaptic membrane and the vesicle proteins allowing the vesicle to be docked stably
• There are alpha helical structure which interact together to form a super helix
• The net effect of this interaction is a stable complex of the vesicle at the
synapse full of neurotransmitter
• The vesicle needs a signal to be release and the signal is CALCIUM
• At these sits of docking of the vesicles you find a high concentration of calcium channels
• Calcium enters through the channel and causes a calcium dependent change in a calcium sensor protein on the vesicle making the complex undergo
conformational change
• This drives the release of transmitter into the synaptic cleft


Describe 3 neurotoxins that target vesicular proteins

Tetanus = SPASTIC paralysis
• It has zinc dependent endopeptidases that inhibit transmitter release
• Botulinum = FLACID paralysis
• Alpha Latrotoxin from the black widow spider also targets vesicle proteins
• 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


How do ion channel receptors and g coupled receptors differ

Ion Channel Receptor = FAST
• G protein coupled receptor = slow
• Ion channel receptors mediate ALL fast excitatory and inhibitory transmission


Give examples of ion channel receptors

Acetylcholine at nicotinic receptors
Glutamate = EXCITATORY - allows influx of SODIUM
• GABA = Inhibitory - allows influx of CHLORIDE
• TWO main types of Glutamate Receptor:
AMPA Receptors
• Responsible for the majority of FAST excitatory synapses
• Rapid onset, offset and desensitisation
NMDA Receptors
• Slow component of excitatory mechanism
• Needs TWO INPUTS for this receptor to become activated


Give examples of g coupled receptors

Acetylcholine at muscarinic receptors
• Dopamine
• Noradrenaline
• 5-hydroxytryptamine
• Neuropeptides (e.g. enkephalin)


Describe An excitatory synapse mediated by Glutamate

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
• 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)
• Abnormal cell firing leads to seizures associated with excess glutamate in the synapse


Describe an inhibitory synapse mediated by GABA

GABA is the main inhibitory neurotransmitter
• GABA and glutamate have very similar structures - removal of carboxyl group
in glutamate gives you GABA
• GABA is synthesised by Glutamic Acid Decarboxylase (GAD) - this is a Vitamin
B6 enzyme
• GABA binds to the receptor and allows the entry of chloride which
hyperpolarises the cell
• 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


What is epilepsy

One of the commonest neurological diseases worldwide
• Caused by abnormal release of glutamate leading to hyperexcitability of cells
• 30% are refractory to treatment


How do anti epileptics work

Epilepsy treatment is focussed on damping down excitatory activity by facilitating inhibitory transmission
• By exploiting the GABA receptor you can produce anti-epileptics, sedatives and muscle relaxants
• There is a binding site for benzodiazepines (e.g. diazepam)
• There is a binding site for barbiturates (used for treatment of epilepsy) - this alters the frequency of channel opening