OCB03-2008 Neurotransmitters 1: Glutamate, GABA & Acetylcholine Flashcards
What is the firing of an action potential determined by?
The number of excitatory and inhibitory synaptic inputs
The strength of the individual inputs
How do synaptic neurons inhibit neurons?
Hyperpolarisation
How do synaptic neurons excite neurons?
Depolarisation
what is glutamate?
A major excitatory neurotransmitter in the CNS
What are the glutamatergic pathways involved in?
Involved in portico-cortical pathways
Pathways between the cortex and thalamus
Involed in pathways between the cortex and striatum
What physical processes are glutamate involved in?
Emotions, memory and cognition
What psychiatric conditions are glutamate associated with?
Depression
Anxiety
Drug addiction
Schizophrenia
How does glutamate access the brain?
It does not cross the BBB so the brain cannot supply glutamate via circulation
Instead is is synthesised by the metabolism of glucose and from glutamine synthesised in astrocytes
How does glutamate work as a neurotransmitter?
Glutamine enters the presynaptic neurone where it is converted into the glutamate via glutaminase
Influx of Ca2+ causes the synaptic vesicles to fuse with the membrane and release glutamate
Glutamate binds to post synaptic receptors and diffuses out of the synaptic cleft and binds to glutamate transporter on the astrocyte
Glutamate is converted back to glutamine via glutamate synthase
Glutamine exits the astrocyte via the glutamine transporter init the ECS
What are the 2 types of glutamate receptor?
Ionotropic and Metabatrophic
What are the glutamate ionotropihic subtypes?
NMDA
AMPA
Kainate
What type of channel is Metabotropic?
GPCR
What is AMPA and Kainate transmission like?
Fast synaptic current with fast decay
Influx Na+ ions cause depolarisation
What is a blockage of AMPA receptors likely to cause?
Inhibitory effect on CNS
What is NMDA transmission like?
Slower onset and slower decay
Higher affinity for glutamate
What is a blockage of NMDA likely to cause?
Effects on behaviour and memory
Why does NMDA have a slower response?
It has a higher affinity for glutamate
Mg2+ blocks the channel at less than -50mV
Depolarisation of AMPA removes Mg2+ block
Why does NMDA continuously active after glutamate concentration is 0?
NMDA has a high affinity for glutamate
How to pre-synaptic glutamate metabatropic receptors work?
Inhibits Ca voltage gated channels so there is less calcium influx into the pre-synaptic terminal and so reduces the amount of neurotransmitter released form other terminals
How to post-synaptic glutamate metabatropic receptors work?
Modifies the activity of K+ channels so changes the number if action potentials
Modulating the excitability of a neurone
What is the consequence of excess glutamate?
Excitotoxicity and ischaemic cell death
What is GABA?
Major inhibitory neurotransmitter
What diseases are associated with loss of GABA?
Epilepsy
Huntington’s disease
Uncontrollable movements
How is GABA formed?
Formed from glutamate by acton of glutamic acid decarboxylase
How does GABA work as a neurotransmitter?
GABA is transported into synaptic vesicles then released during an action potential
It diffuses across the synaptic cleft and interacts with receptors
It diffuses back into the astrocyte via GABA transporters
What are the two GABA receptors?
Ionotrophic GABAA receptors
Metabotropic GABAB receptors
Where are GABAA receptors found?
Post-synaptically
Where are GABAB receptors found?
Pre and post synaptically
How do GABAA mediate inhibition?
They allow chloride ions to flow into the cell which:
Hyperpolarises the neuron
Inhibits depolarisation
What can block of GABAA cause?
Convulsions (involuntary contraction of muscles)
What drugs enhance opening on GABAA chloride channels?
ethanol
Benzodiazepines
GA
How do GABAB receptors work?
Coupled to Gi so when activated inhibits adenylate cyclase
Which GABA receptors is longer-lasting?
GABAB
What does presynaptic inhibition cause?
Inhibiton of voltage-gated Ca2+ channels which decreases transmitter release
What does post-synaptic inhibition cause?
Increased opening of K+ channels which reduced firing of action potentials
How is acetylcholine formed?
Acetyl and choline combine via choline acetyltransferase to form acetylcholine
How is acetylcholine broken down?
It is hydrolysed by acetylcholinesterase and choline is taken up pre-synaptically
What receptors do ACh act on?
Nicotinic and muscarinic
What subunits make up the nicotinic receptor?
2 alpha
3 beta
Which subunit of nicotinic receptor does acetylcholine bind to?
alpha
What occurs when ACh binds to a nicotinic receptor?
Causes a conformational change and increased permeability to Na+, K+ and Ca2+
K flows out and Na and Ca flow in
What is the presynaptic effect of ACh binding to the nicotinic receptor?
Neurotransmitter release
What is the postsynaptic effect of ACh binding to the nicotinic receptor?
fast excitation and depolarisation
How do M1, M3 and M5 work?
They are linked to phospholipase C activation which controls calcium release
How do M2 and M4 work?
Inhibits adenylate cyclase
