Synaptic Transmission: Pre-synaptic Flashcards
What are the six major classes of neurotransmitter receptors?
- Cholinergic
- Biogenic amines
- Amino acids - GABA, Glu, Asp, Gly
- Purinergic - ATP / adenosine
- Peptides
- Dissolved gases: NO / CO
What are the types of biogenic amines? How are they made?
- Adrenergic - includes dopamine, NE, E
- Serotonin
- Histamine
Made via hydroxylation or decarboxylation of amino acids
What is one possible etiology of Alzheimer’s intellectual deterioration?
Reduction in levels of choline acetyl-transferase, which makes ACh from Acetyl-CoA + Choline.
What amino acid is used to make nitric oxide?
Arginine
What is the catecholamine synthesis pathway?
True Love Does Not End
Tyrosine -> L-DOPA -> Dopamine -> NE -> E
What is serotonin made from?
Tryptophan
What is histamine made from?
Decarboxylation of Histamine
What is GABA made from? Why is this interesting?
Decarboxylation of glutamate. Interesting because glutamate is stimulatory and GABA is inhibitory.
What is the treatment for Parkinson’s and why does this work?
Give L-DOPA, this works because parkinson’s patients have low dopamine levels in brain, and Tyrosine hydroxylase is the rate-limiting step of catecholamine synthesis.
What cofactor is required for tyrosine hydroxylase (TH) action? What inhibits this binding?
Biopterin, inhibited by norepinephrine (feedback inhibition)
How do calcium or cAMP modify tyrosine hydroxylase activity? What additional effect can cAMP have?
Ca (via PKC) or cAMP activate a kinase which phosphorylates tyrosine hydroxylase, preventing the the norepinephrine interference of biopterin binding.
cAMP can also bind cyclic AMP response element binding protein (CREB) which binds the response element to induce additional transcription of TH
What amino acids normally surround neuropeptide precursors to mark for cleavage via endopeptidases?
Dibasic amino acids lysine-arginine
What amino acid is included at C terminal of neuropeptides and why?
glycine, as a precursor for amidation to prevent exopeptidases from degrading it.
What are enkephalins?
Opoid peptides of 6 amino acids, which are part of many different more complex opoids like beta-endorphin, dynorphines, and neoendorphin.
What are some precursors to enkephalins?
POMC, pro-enkephalin, pro-dynorphin, each with one or more copies of enkephalins.
What is an example of alternative mRNA splicing?
Either POMC for its many hormones, or Substance P, which comes from the same mRNA as substance K but is sliced at a different spot.
Can neurons contain more than one neurotransmitters?
Yes, and they often appear in specific combinations with different type (i.e. ACh neurotransmitter with VIP (peptide))
What do adrenergic vesicles contain?
Epi, norepi, chromogrannins to hold them and concentrate them, and dopamine beta-hydroxylase to make the epi
What are vSNARE and tSNARE and how do they associate / dissociate? Name the important proteins!
vSNARE = on vesicle = VAMP / synaptobrevin tSNARE = on target (membrane) = syntaxin / SNAP25
Associate spontaneously via calcium-dependent activation of synaptotagmin on vesicle surface, allowing vSNARE (i.e. synaptobrevin) to hydrophobically interact with tSNARE on membrane surface. ATP is expended to break this interaction
What normally prevents neurotransmitter vesicle fusion to the surface?
Various proteins block vesicle fusion until mediated via syntaptotagmin
What is the RIM protein?
It tethers the vesicle near the Ca channel to ensure high local calcium concentration to trip neurotransmitter release
How does botulinum toxin work?
Proteases that inhibit release at cholinergic endings by cleaving specific sequences on tSNARE and vSNARE. Can treat muscle spasms.
How does tetanus toxin work?
Reduces GABA and glycine synapses via vSNARE cleavage, which are inhibitory neurotransmitters.
What is the function of clathrin for neutotransmitters?
Endocytosis of clathrin-coated vesicles, which will fuse with membrane endosome sytem from which NT vesicles bud off
What is the “Kiss and run” vs classical pathway
Kiss and run is release of some NT in vesicle without full fusion. ATP is required to break the tSNARE/vSNARE interaction, and is carried out by the NSF protein.
What are the three main methods of neutrotransmitter signal termination?
- Diffusion away - as in metabolic hormones
- Enzymatic degradation in synaptic cleft (i.e. acetylcholinesterase)
- Reuptake - i.e. norepinephrine, serotonin
How is GABA reuptake strange?
GABA is reuptaken via glial cells
How was myasthenia gravis originally treated?
Via neostigmine - blocked acetylcholinesterase to make ACh last longer in synaptic cleft and stimulate the fewer ACh receptors (due to autoimmunity.)
What is an additional possible fate of neurotransmitters taken up by the presynaptic ending? What was one disease where this was important?
Further metabolization, as in dopamine’s conversation to HVA via monoamine oxidase and catechol-O-methyltransferase.
This is important in Parkinson’s because decreased HVA levels were a signal that Parkinson’s was a defect in dopamine levels.
Where is dopamine deficiency commonly found in Parkinson’s? What does this nuclei innervate?
Substantia nigra degrades. It gives extensive innervation to the striatum, an area of the forebrain basal ganglia involved in motor / rewards.
What area has the highest concentration of the cholinergic neurons? What deficiency occurs here?
Nucleus basalis of Meynert. These axons project to the neocortex, along with adjacent groups of cells which project to olfactory cortex and hippocampus. These pathways degrade in Alzheimer’s. NOTE: short axons to neostriatum (i.e. putamen, caudate, accumben do not degrade in Alzheimer’s).
Where do neurons synthesizing NE reside? What do they innervate?
In the pons and medulla, most prominently in the locus ceruleus (50% of NE neurons in the brain). innervate entire neocortex, cerebellum, spinal cord
Where in the brain is serotonin prominently found and what is its function?
Raphe nuclei, found all around the brainstem + midbrain. Function to make motor neurons more excitable and dampen pain.
Where are opioids in the highest concentration of the brain?
I.e. enkephalins, highest concentration in the globus pallidus of basal ganglia. The lateral part is almost completely knocked out in Huntington’s.
