Neurotransmitters Flashcards
What are receptors?
Membrane-spanning proteins comprising a number of subunits
What does ligand binding induce in a receptor?
A conformational change
What is the hypothesis for the binding of a neurotransmitter?
lock and key hypothesis
What does an agonist do?
can bind to, and activate the receptor. Generally has a similar structure to natural ligand
What does a partial agonist do?
binds and activates the receptor, but with reduced efficacy compared to agonist.
What does an antagonist do?
binds to, but cannot activate receptor; occupies the natural ligand site so it cannot bind
What does an allosteric modulator do?
binds the receptor at a different site to alter how receptor responds to ligand (can have positive or negative allosteric modulators)
Give features of the nicotinic acetylcholine receptor and how it depolarises
- ligand gated ion channel
- Membrane-spanning protein
- Ionotropic
- Five subunits (2a, B, gamma, epsilon, sigma) arranged to form a pore
- 2Ach binds 2a subunits to open channel
- Na+ (and K+) flow down their electrochemical gradient
- Membrane depolarises (epsp)
- There is a huge diversity of subunits and hence receptors
What are the things that something must have in order for it to be identified as a neurotransmitter?
- Must be synthesised by the neuron
- Must be present in synaptic terminal at sufficient concentrations
- Must be released on presynaptic stimulation
- Exogenous application to postsynaptic cell evokes a response
- Mechanism exists for its removal from synaptic cleft
What are the three main classes of neurotransmitters?
- Amino acids: e.g. glutamate; glycine’ y-aminobutyric acid (GABA) (synaptic vesicles, 50 nm)
- Amines: e.g. acetylcholine (Ach); dopamine; noradrenaline; serotonin (synaptic vesicles
- Peptides: e.g. enkephalin; substance P; neuropeptide Y (dense-core secretory granules, 100nm)
What is co-localisation?
Most synaptic terminals contain multiple neurotransmitters, usually one amino acid, one amine and a few peptides
What are the amino acid neurotransmitter functions?
Glutamate – excitatory
GABA – inhibitory
What are the amine neurotransmitter functions?
Acetylcholine – NMJ, brain
Dopamine – movement
Serotonin (5-HT) – sleep, appetite, arousal
What are the peptides neurotransmitter functions?
Enkephalin – opiate
Substance P – pain
What type of neurotransmitter is the speed of action fastest with and what type is it slowest with?
Speed of action fastest with amino acids and slowest with peptides
Where are most neurotransmitters synthesised?
in the terminal, not the cell body
What is the general synthesis of neurotransmitters?
- Enzymes and transporters in terminal
- Enzymes convert precursors in neurotransmitter in cytosol
- Transporters load neurotransmitter into vesicles
What are three ways in which neurotransmitter is removed from the synaptic cleft?
- Diffusion: e.g. small amines and amino acids (gets excreted
- Reuptake: specific neurotransmitter transporter proteins in terminal and glial membranes. E.g. Choline transporter (reuse transmitter)
- Enzymatic degradation in cleft – followed by uptake of precursors e.g. acetylcholinesterase (AChE) (reuse transmitter)
Give features of GPCR effector signalling
- Neurotransmitter activation of a GPCR at the postsynaptic membrane activates a specific G-protein
- GPCRs allow more possibilities in terms of cellular responses and can amplify responses
- G protein activation leads to ion channel gating; ion channel modulation; enzyme activation; activation of secondary paths
What do fast and slow excitation in postsynaptic cells do?
- Postsynaptic cell contains both nicotinic and muscarinic receptors
- As an action potential arrives in presynaptic cell acetylcholine is released
- First we see a Fast EPSP due to nicotinic receptor
- Then we see slow EPSP due to muscarinic receptor
- This first EPSP is not enough to take the cell to action potential threshold
- When presynaptic cell fires again in rapid succession the second EPSP will occur over the initial slow EPSP so action potential threshold will be reached
Give features of Glutamate
- excitatory
- four different types of receptor:
- AMPA receptor: requires glutamate to open and then allows Na+ influx
- NMDA receptor: requires glutamate PLUS depolarisation to open and then allows Ca2+ and Na+ influx. Needs magnesium to be pushed out to open
Kainate receptor: ionotropic Na/K channel
mGluR receptor (3 classes): metabotropic
What are the different types of GABA receptor and what are they a key target for?
GABAA – ionotropic, increase Cl-, fast inhibition
GABAB metabotropic, increase K+, Decrease Ca2+, inhibition ‘SLOW’
A key target for therapeutic drugs e.g. anticonvulsants, anti-anxiety – allosteric modulators
Are dopamine receptors metabotropic or ionotropic?
metabotropic
What are autoreceptors, what do they do and how?
- Autoreceptors are a type of presynaptic receptor
- Autoreceptors are receptors for the neurotransmitter released by the nerve terminal in whose membrane they reside, and when activated these receptors regulate the release of that neurotransmitter
- Usually this takes place in the form of inhibition i.e. negative feedback, but there are some instances when positive feedback is seen
- Though the presynaptic autoreceptor binds the same neurotransmitter as the postsynaptic receptor, it is often a different member of the same receptor family.
