What are the main categorie of NTs?
1. biogenic amines (ACh, monoamines, amino acids like GABA, Nucleotides like ATP and other htings like NO and CO)
2. neuropeptides (opioid peptides, pituitary peptides, tachykinins, glucagon, angiotensin 2, etc)
What are the differences between a classical small molecule NT and a peptide NT?
Different in synthesis and packaging...
Small molecule: enzymes made in cell body, send down by slow axonal transport, NT synthesized in the terminal, packaged in small vesicles, and released
Peptide: enzymes and peptide precursors are assembled in the cell body, sent down by microtubule tracks, in the terminal the enzyes modify the precursors to make the NT, packaged in larger, denser vesicles and released
What criteria are used for identifying an NT?
1. NT has to be present in the presynaptic terminal
2. has to be released upon stimulation
3. have to be reeptors for it on the post synaptic cells
4. if you apply the NT or an analog, there has to be a response
What is the metabolic pathway for glutamate biosynthesis?
1. In the terminal, glutamine is converted to glutamate by glutaminase
2. Glutamate is pacakged into a vesicle by VGLUT
3. Vesicle fuses and releases glutamate into the cleft
4. Glutamate acts on receptors or is taken up by nearby glia through the EATT transporter
5. In the glia, glutamate is converted back to glutamine by glutamine synthetase
6. Glutamine is transported back into the neuron temrinal through another EATT
What are the subtypes of glutamate receptors?
What are the key features of the NMDA receptor?
It is a glutamate receptor
It requires both glutamate and lysine to open - and it needs to be in a depolarized membrane
It allows Na+ and Ca+ to enter the cell, thus it is depolarizing and excitatory
Involved in long term potentiation of memory
How are glutamate receptors involved in ischemic cell damage?
In stroke, the brain will attempt to keep working and the neurons will fire and release their glutamate. THe issues is that the glutamate won't be taken back up and the receptors will open, allowing Ca2+ to rush into the cell catastrophically - this damages the nucleus and mitochondria vecuase it causes an increase in NO radicals and arachidonic acid, also thorugh osmotic pressure - the cell dies and lyses
What is an excitotoxin?
An NT that act as an excitatory NT in the brain. If something happens and too much is released/it's not taken up appropriate, this will be toxic to the cell
How is the NT glutamate inactivated?
It's taken up in the glia and converted to glutamine
What role do glutamate receptors play in human disease?
What neurodegenerative disorders involve glutamate receptor activation?
What is th emajor inhibitory NT in the brain?
GABA and glycine
What proteins do tetanus and botulinum affect?
the SNARes - proteins involved for docking and fusion or NT vesicles
THe toxins are Zn proteases, so they break them down
this means there's no release of inhibitory GABA
What does latrotoxin come from and what is its effect?
from the black widow spider
it allows NT vesicles to fuse and release without the usual calcium influx trigger = constant GABA release = paralysis
What receptors do endocannabinoids work on and how is this a special signalling pathway?
it's special because it's a RETROGRADE MESSENGER
it's synthesized in and released from the POSTSYNAPTIC terminal after Ca2+ influx and it diffuses backwards to work on the CB1 receptor on the PRESYNAPTIC terminal
this is coupled with a G-protein that increases calcium influx to cause depolarizaiton and more NT release