Neurotransmitters and Receptors Flashcards
What is a classical neurotransmitter?
Act quickly- produce fast EPSPs and IPSPs which last a few milliseconds
What are modulators?
Act slowly- modify the actions of classical transmitters- produce slow EPSPs and IPSPs which can last for several hundred milliseconds or even longer
What do modulators often act through?
G-protein coupled receptors
What are some examples of classical neurotransmitters?
Acetylcholine
Amino acid transmitters
What are the two groups classical neurotransmitters can be separated into according to their actions?
Excitatory transmitters- e.g. L-glutamte
Inhibitory transmitters- e.g. GABA (γ-aminobutyric acid)
What are some examples of modulators?
Monoamines (noradrenaline, dopamine, serotonin) and neuropeptides (e.g. substance P, enkephalin) are examples of modulators.
What is the criteria in order to determine if a substance is a neurotransmitter or modulator?
It must be synthesised in the presynaptic neuron - high concentrations of the
substance must also be present in axon terminals of the presynaptic neuron
It must be released from the presynaptic terminal
It must have an action on the postsynaptic membrane, i.e. it must activate
receptors
It must be inactivated
Where are transmitters stored?
In vesicles in the presynaptic membrane
Where are small molecule transmitters synthesised?
In axon terminals
How are transmitters formed?
Precursor molecules (e.g. choline is a precursor for acetylcholine) are converted to the transmitter by enzymatic action (in the case of acetylcholine the enzyme is choline acetyltransferase)
Where are neuropeptides synthesised?
In the cell body
How are neuropeptides formed?
Initially produced as large polypeptides and are enzymatically split into smaller peptide molecules
These are transported to the nerve terminals by anterograde axonal transport
What is essential for transmitter release?
Calcium ions
What happens when the presynaptic membrane depolarises?
Precedes release and voltage-gated calcium channels open
What do calcium ions do when they enter the presynaptic membrane?
Enter and initiate transmitter release
What happens if other cations are used e.g. magnesium ions?
Release is blocked
What are miniature endplate potentials (MEPPs)?
Tiny spontaneous potenitals
Can be recorded with micropipettes at the postsynaptic membrane of the neuromusclar junction
What happens to MEPP is one packet of transmitter is released?
A unitary MEPP (which always has the same amplitude) is observed
What happens if two packets of transmitter is released?
MEPP is twice the amplitude of the unitary MEPP …… and so on for three and four packets.
What does the evidence of packets of transmitter and it effect on MEPP show?
Release of transmitter is quantal, i.e. transmitters are released as uniform packets.
What does the contents of a single vesicle correspond to?
A quantum of transmitter
Where are autoreceptors?
Present at the presynaptic membrane
What are autoreceptors activated by?
The transmitter released from the same terminal
What can autoreceptors influence?
Release by regulating transmitter production
Where do transmitters activate receptors?
The postsynaptic membrane
What are the receptors on the postsynaptic membrane?
Protein molecules embedded in the membrane and have active sites in the extracellular space
What do neurotransmitters specifically bind to?
Active sites on receptors
What are the two classes of receptor?
Ionotropic
metabotropic (G-protein coupled)
What are ionotropic receptors?
Ion channels with active sites for neurotransmitters on them
What happens when a neurotransmitter binds to an active site on an ionotropic receptor?
The channel opens and ions pass through
What happens when the transmitter dissociates from the receptor on an ionotropic receptor?
The channel closes
How do ionotropic receptors act?
Quickly and are associated with fast transmission
E.g. nicotinic aceytlcholine receptor
What are metabotropic receptors?
Complex and not directly linked to ion channels
What do metabotropic receptors use?
“second messengers” (E.g. cyclic-AMP)
What do second messengers activate in metabotropic receptors?
Activates an effector system which opens the ion channel
What kind of receptors are metabotropic receptors?
Operate slowly, hence the slow action of neuromodulators
e.g. muscarinic acetylcholine receptor
What can second messengers trigger for metabotropic receptors?
Other events in addition to opening ion channels
These events are known as cascades and often result in long-term changes
Cascades are important in learning and memory
Why is precise timing important for synaptic action?
Transmitter action must be stopped quickly
What are the 3 mechanisms of inactivation?
Specific enzymes, e.g. acetylcholine is broken down by acetylcholine esterase
Specific uptake by neurons or glial cells, e.g. monoamines are taken up by neurons and recycled
Diffusion, e.g. peptides can diffuse for considerable distances