Lecture 8: Presynaptic Processes Flashcards
What are neurotransmitters? What are they released into?
chemical signals released from presynaptic nerve terminals into the synaptic cleft
How is a signal passed on from one neuron to the next?
release of one (or more) chemicals from the axon terminal -> these chemicals act on receptors of the target cell to temporarily change the properties of that cell i.e. change in membrane potential or conductance
What are the criteria that must be met in order for a chemical to be considered a neurotransmitter?
synthesis: must be produced within a neuron
storage: must be found within a neuron
release: must be released when the neuron is depolarised
receptor: must act on a post-synaptic receptor and cause a biological effect
inactivation: there must be a mechanism for inactivation (uptake / degradation)
if applied on a post-synaptic membrane, it should have the same effect as when released by a neuron
What are examples of classical (small molecule) neurotransmitters?
amino acids such as glutamate, GABA and glycine
monoamines such as noradrenaline, dopamine, adrenaline and serotonin
acetylcholine
What are examples of non-classical (large peptide) neurotransmitters?
peptides such as substance P, somatostatin, enkephalin and kisspeptin
gases such as nitric oxide and carbon monoxide
lipids such as anandamide
How are classical and non-classical neurotransmitters synthesised?
classical: uptake or enzymes
non-classical: protein synthesis
How long is the duration of action for classical and non-classical neurotransmitters?
classical: fast and short
non-classical: slow and long
What are the vesicles like for classical and non-classical neurotransmitters?
classical: small (filled by transporters)
non-classical: large (secreted proteins from RER)
What is the sequence of events involved in neurotransmission?
NT synthesised and stored -> AP -> depolarisation and opening of VGCC -> Ca2+ influx -> vesicles fuse with presynaptic membrane -> NT released via exocytosis -> NT binds receptors on postsynaptic membrane -> postsynaptic channels open -> postsynaptic current causes EPSP or IPSP -> reuptake and / or breakdown of NT
What do VGCCs couple?
couple membrane depolarisation to NT release
Ca2+ that enters binds to release proteins to cause vesicle fusion
What are the different types of VGCCs?
N-type (Cav2.2) - classical blocker: conotoxin (cone snails)
P/Q (Cav2.1) - classic toxin agatoxin (spiders)
How are neurotransmitters released and what is this known as?
NTs are released in packets and this is known as quantal release
Neurotransmitters are released in packets. What does this determine?
determines the minimum size of a postsynaptic potential (EPSP or IPSP in neurons)
What is an mEPP?
the change in the membrane potential of a muscle cell produced by a single quantum is called a miniature end-plate potential
What is a quantum?
the amount of neurotransmitter in 1 vesicle
How big is an mEPP? What implication does this have upon neurotransmitter release?
an mEPP is only about 1/100 the size of the end-plate potential (EPP) produced by electrical stimulation of the entire nerve innervating the muscle fibre
therefore, normal neurotransmission results from the release of many vesicles simultaneously
What is the relationship of synaptic vesicle exocytosis and quantal transmitter release?
there is a 1:1 ratio between the number of vesicles fusing and the number of quanta being released
What does low frequency stimulation lead to?
preferentially raises the Ca2+ concentration close to the membrane favouring the release of transmitter from small clear-core vesicles
What does high frequency stimulation lead to?
more general increase in Ca2+ concentration causing the release of neuropeptides from large dense core vesicles as well as small molecule neurotransmitters
What is the process of co-release?
both neurotransmitters are packaged into the same set of synaptic vesicles
when the presynaptic terminal is depolarized it causes the release of both neurotransmitters
What is the process of co-transmission?
requires transmitters to be packaged into distinct synaptic vesicles with differential release mediated by differential Ca2+ sensitivity
alternatively, co-transmission can rely on spatial segregation of vesicle populations to different boutons to different synaptic targets
What is the cytoplasmic surface of the vesicle membrane covered in?
densely covered in proteins which act at one or more steps in the synaptic vesicle cycle
What is the role of synapsin?
may keep vesicles tethered within the reserve pool by crosslinking vesicles to each other and to actin filaments in the cytoskeleton
What is the structure of a SNARE complex?
synaptobrevin (vesicular SNARE)
syntaxin (plasma membrane SNARE)
snap25 (plasma membrane snare)
synaptotagmin (vesicular Ca2+ binding protein)
What is a SNARE?
a SNAP receptor
What is the kiss-and-run model of synaptic vesicle recycling?
vesicles transiently fuse with the plasma membrane
after neurotransmitter release, the fusion pore is closed and the vesicles are recovered
What is the clathrin-mediated endocytosis model of synaptic vesicle recycling?
a synaptic vesicle fuses and collapses into the membrane
a new vesicle is formed in a region distant from the fusion site
What is the new model of synaptic vesicle recycling?
after a rapid internalization of the membrane via ultrafast endocytosis, the vesicle membrane is delivered to an endosome
clathrin-mediated regeneration of synaptic vesicles occurs at the endosome
