Neurotransmitters Flashcards
who proved the basis of chemical transmission?
describe his experiment
Otto Lewi in 1992
he took an isolated frogs’s heart with its vagus nerve connected
if he electrically stimulated the vague nerve
-> could alter the contraction of the heart
made a cut through the vague nerve to break the electrical connectivity to the heart muscle
removed the bathing solution surrounding the original
-> showed that the solution could mimic the electrical excitability seen when the nerve was connected
what was Loewi postulating?
what was the soluble molecule in the solution surrounding the heart in Loewi’s experiment?
the electrical stimulation of the heart was releasing some sort of messenger that was driving the contraction
acetylcholine
what are neurotransmitters?
what are the 2 fundamentally important synapses?
endogenous chemicals
which transmit signals from a neurone to a target cell
across a synapse
axodendritic
neuromuscular
what are the 3 stages leading to post-synaptic signal?
- presynaptic action potential
- depolarisation of synaptic terminal
- release of chemical transmitter
- postsynaptic signal
what are the major neurotransmitters of the mammalian brain?
what are the synapses that use these called?
glutamate
(glutamatergic)
GABA
(GABAergic)
ACh
(Cholinergic)
Noradrenaline
(Noradrenergic)
Dopamine
(Dopaminergic)
5HT (serotonin)
(Serotonergic)
what is the composition of ACh?
what is required for this to form?
an ester of acetic acid and choline
blood supply to brain, brings choline
what are the 3 amino acid neurotransmitters?
are they inhibitory or excitatory?
which NT is a glutamate derivative?
which purine is a NT?
glutamate
(excitatory)
aspartate
(excitatory)
glycine
(inhibitory)
GABA
ATP
which amino acid are catecholamine NTs synthesised from?
what are these NTs?
tyrosine
dopamine
noradrenaline
adrenaline
which indoleamine is an NT?
which amino acid is this synthesised from?
which imidazoleamine is an NT?
serotonin
tryptophan
histamine
what criteria define a ‘classical’ NT?
- synthesis
- regulated synthetic machinery in the nerve terminal - storage
- in secretory vesicles - release
- regulated release into the synaptic space - reception
- presence of receptors - removal
- a means for terminating the action
describe the life cycle of a typical NT
- synthesis of NT at nerve terminal
- packing of NT into small vesicles
- action potential depolarises membrane -> Ca2+ influx
- > triggers fusion and release of vesicles - NT interacts with postsynaptic receptors
- clearance system
e. g. uptake via transport system into a glial cell
what are autoreceptors?
receptors in the presynaptic membrane of the nerve terminal
bind the release signal molecule
to regulate further NT release
describe the synthesis and vesicular packaging of glutamate
what type of gradient does this require?
glutamine
-> glutamate
using glutaminase
VGluT
(vesicular glutamate transporter)
actively transports glutamate into the vesicles
proton gradient
how is ACh synthesised?
from acetic acid and choline
via choline acetyl transferase (ChAT)
describe what happens at a cholinergic synapse
ACh is synthesised + packaged into vesicles
vesicles fuse with membrane + release ACh into synapse
binds to nicotinic or muscarinic postsynaptic receptors
signal is propagated until ACh is terminated via enzymatic degradation by AChE
(acetylcholinesterase)
what does AChE produce?
where is it located?
what happens to choline?
why?
acetate and choline
lipid-anchored to presynaptic membrane
taken back up by a transporter
it is a limiting resource
- relies on delivery via blood from diet
- so makes sense to recycle it
what is AChE a primary drug target for?
treating Alzheimer’s disease
inhibition of AChE
- > maintains ACh levels
- > prolongs cholinergic signalling
what cognitive process are glutamatergic synapses responsible for?
memory
describe glutamate synthesis
how is this packaged into vesicles?
when do these vesicles fuse with the membrane?
glutaminase converts glutamine into glutamate
via the VGluT
when the membrane is depolarised
which post-synaptic receptor sub-types does glutamate interact with?
AMPA receptors
NMDA receptors
mGlu receptors
what are AMPAR and NMDAR both classed as?
which ions interact with the receptors?
glutamate-gated ion channels
AMPA = sodium NMDA = sodium + calcium
where did the AMPA and NMDA nomenclature come from?
NMDA and AMPA are chemical analogs of glutamate
- they don’t exist in the mammalian nervous system
- but are synthetic chemicals that can distinguish between the 2 receptor sub-types
what is the basic structure of mGlu?
what is is responsible for?
7 transmembrane spanning receptor
slower signalling
- metabolic processes
how is glutamate taken up by astrocytes (glial cells)?
what happens to glutamate in the glial cell?
EAATs
(excitatory amino acid transporters)
glutamate converted to glutamine
via glutamine synthatase
