T1L6 chemicals in the brain Flashcards
vesicular release
- action potential causes Ca2+ to flow into cell
- Ca2+ activates CaMKII (phosphorylates synapsin)
- this releases vesicle from cytoskeleton
- SNARE complex binds the vesicle to the membrane of the active site using synaptotagmin
- vesicle then recovered by endocytosis, is refilled and reused
synapsin
holds vesicle to cytoskeleton. phosphorylated by CaMKII
CaMKII
calcium calmodulin activated kinase II
- phosphoyates synasin
SNARE
fuses vesicle to membrane of active site
- synaptotagmin
clostridal toxins
eg tetanus toxin, botox
- cleavage of snare complex
- no exocytosis so no neurotransmitter release
tetanus toxin
- inhibits release of glycine and GABA at inhibitory neurons, resulting in disinhibition of cholinergic neurons – so permenantly contracting muscle
botox
- acts on neuromuscular junction. muscle becomes permanently relaxed
- botulinum toxin
4 categories of neurotransmitter
amino acids monoamines acetylcholine ( synthesized in presynaptic terminal, stored in synaptic vesicles, released in response to LOCAL ca2+) - fast
neuropeptides
(synthesized in the cell soma and transported to the terminal, stored in secretory granules, released in response to GLOBAL ca2+)
- slow
low frequency impulses
activate fast transmitters eg glutamate
- local ca2+ increase
don’t activate slow transmitters eg neuropeptide
high frequency impulses
activate both types of neurotransmitter
- global ca2+ increase
amino acid transmitters
1) excitatory
- slightly depolarises postsynaptic cells membrane
- glutamate (Glu)
2) inhibitory
- slightly hyperpolarises the postsynaptic cells membrane
- GABA (brain)
- glycine (gly)
diffuse modulatory systems
- eg serotonergic system
function in:
- mood
- sleep
- pain
- emotion
- appetite
glutamate (glu)
- synthesized in presynaptic terminal from kerbs cycle and from glutamine converted by glutaminase to glutamate
- loaded and stored in vesicular glutamate transporters
- reuptake by excitatory amino acid transporters (EAATS)
- EXCITATION
GABA
- synthesized from glutamate in a reaction catalysed by glutamic acid decarboxylase (GAD)
- cleared from synapse by reuptake using transporters
regulation of amino acid neurotransmitter release
too much Glu/ too little GABA»_space; hyperexcitability and epilepsy exotoxicity
cerebral ischaemia:
- metabolic events that maintain electrochemical balance are destroyed
- reverse NA/K gradient
- transporters release glutamate by reverse operation
- cell death
GHB
- date rape
- GABA metabolite that can be converted back to gaba
- unconsciousness and coma
MONOAMINES 2 categories
catecholamines:
- (dopamine, adrenaline, noradrenaline)
- loaded into vesicles by vesicular monoamine transporters (VMATs)
- released by ca2+ dependant exocytosis
idolamines:
- (serotonin)
- stored in vesicles
catecholamine synthesis - dopamine and adrenaline
pic slide 28
idolamine synthesis - serotonin
pic slide 33
ACETYLCHOLINE
eg acetylcholine
- choline acetyltransferase converts choline + acetylcoa to acetylcholine
- choline transported back into presynaptic terminal after release; converted bac into acetylcholine
- amount of choline is rate limiting step
NEUROPEPTIDES
- synthesized in cell soma and transported to terminal
- stored in secretory granules
- released in response to GLOBAL ^Ca2+
- they are short polypeptide chains 3 to 36 aa
- over 100 described
- slow transmission
- released following the secretory pathway– different to small molecules
- vesicle membrane recycled but not reused
- signal terminated by neuropeptides diffusing away from synapse and degredation by proteases
- effect is longer duration
neuropeptide vs small molecule synapse comparison
pic s41
soluble gases as neurotransmitters
eg no/co
- no made in postsynaptic neuron by nitric oxide synthase
- not stored and rapidly diffuses
- diffuses between cells
- converted to inactive compound
- useful for coordinating multiple cells in small region
endocannabinoids
- small lipids
- reduce gaba at inhibitory terminals
