Synthesis, Storage, and Release of Neurotransmitters Flashcards
What is the process of synaptic transmission?
nt packaged in vesicle> docking> priming> exocytosis> endocytosis
What is an electrical synapse?
passive communication via direct electrical coupling of 2 cells through gap junctions
What is a chemical synapse?
communication through release and binding of molecules (NT)
What is the name of the pore forming proteins that connnect 2 cells?
connexins
Multiple connexins make a …
connexon
Two connexons make a ….
gap junction
What is the limitation of electrical synapses?
postsynaptic = presynaptic (identical signal, less plasticity)
What is the advantage of electrical synapses?
rapid signal transmission
What is the limitation of chemical synapses?
slower signal transmission
What is the advantage of electrical synapses?
postsynaptic signal varies from presynaptic signal
What are the 6 types of neurotransmitters?
- Ach
- amino acids
- purines
- biogenic amines
- gases (NO, CO)
- peptides
What are NT regulators?
BDNF and NGF
What are the 2 types of amino acid transmitters?
inhibitory and excitatory
What are the characteristics of inhibitory transmitters?
- GABA and glycine
- IPSPs, influx of Cl- or efflux of K+
What are drug examples of inhibitory transmitters?
- phenobarbital
- diazepam
- vigabatrin
What are the characteristics of excitatory transmitters?
- glutamate, aspartate, Ach, serotonin, histamine
- associated primarily with EPSPs
What are drug examples of excitatory transmitters?
- ketamine
- riluzole
- MSG
What are the 5 peptide NT?
- brain out
- opioid
- pituitary
- hypothalamic-releasing
- miscellaneous
What are the biogenic amines?
- catecholamines
- histamine
- serotonin
What is the life cycle of a NT?
synthesis -> packaging -> release -> binding -> inactivation
What is the rate limiting enzyme for the synthesis of catecholamines?
tyosine
In the synthesis of histamine and seratonin, what does a low 5HT cause?
- depression
- OCD
- ADHD
What occurs in the synthesis of small molecule transmitters?
- synthesis of enzymes in cell body, then transported to presynaptic nerve terminal
- slow axonal transport of enzymes
- synthesis and packing of nt
- release and diffusion of nt
- tranpsort of precurors into terminal
What occurs in the synthesis of peptide transmitters?
- synthesis of precursors/enzymes
- transport of enzymes and pre-peptides down microtubule tracks
- enzymes modify pre-peptides to produce peptide nt
- nt diffuses away and is degraded by proteolytic enzymes
The packaging of nt include what 2 vesicles?
clear-core and dens-core
What are clear-core vesicles?
- small molecule transmitter synthesized at presynaptic nerve terminal
- transmitters stored in endosomes which bud off small, clear-core vesicles
What are dense-core vesicles?
- large propeptide transmitters synthesized in cell body with enzymes packaged together in dense-core vesicles
- bud off from golgi and transported along axon
What does the vesicle docking complex include?
- vSNARE
- SNAPs
- tSNARE
What is a vSNARE?
- aka synaptobrevin
- botulism target
- many types of SNAREs
- vesicle docking with presynaptic membrane
What is a SNAP?
- soluble NSF attachment protein
- NSF cofactors
What is a tSNARE?
target membrane; AKA syntaxin
Docking and release of vesicles involves what 2 things?
vSNARE and tSNARE
What happens during fusion and release (exocytosis)?
- AP triggers increase in Ca+
- synaptotagmin acts as the Ca+ sensor and binds
- Ca+ bound synaptotagmin induces vesicular and plasma membrane fusion via interaction with SNAP-25
What are the 2 important proteins involved in endocytosis?
clathrin and dynamin
What is the role of clathrin?
coats membrane and begins process of endocytosis
What is the role of dynamin?
“molecular scissor” which pinches vesicle off membrane
What are the characteristics of clostridial neurotoxins?
- cleave SNAREs
- botulism toxim: blocks exocytosis of Ach vesicles
- multiple targets: synaptobrevin, syntaxin, SNAP-25
What are the 3 methods of inactivation?
- diffusion of transmitter from synaptic space
- cleaving the transmitter into inactive constituents
- reuptake of transmitter back into the presynaptic neuron via transporters
What is the neuromuscular junction?
- voluntary neuronal stimulus from CNS
- AP leads to alpha motor neuron stimulation
- Ach released at postsynaptic membrane in neuromuscular junction
What are endplate potentials?
- depolarizations of muscle fibers caused by Ach binding to postsynaptic membrane
- AP fires -> Ach released -> muscle depolarizes and contracts
What are the characteristics of nicotinic Ach receptors?
- ligand gated
- 2 Ach molecules bind to a single receptor
- receptor changes conformation to open an ion channel that is equally permeable to Na+ and K+
What is the make-up of nAch receptors?
functional receptor has 5 subunits where each winds around through plasma 4 times
What is the process of a neuromuscular junction?
- alpha motor neuron stimulation releases Ach
- activation of nAch receptor
- depolarizing end plate potential
- firing of skeletal muscle AP
What is Myasthenia Gravis?
- autoimmune disease where Abs targeted against nAch receptors on the postsynaptic membrane
- pathological effects of nAch receptor blockade
What are the symptoms of Myasthenia Gravis?
muscle weakness, fatigue, drooping of eyelids
What are the precursors, enzymes, and products for biogenic amines?
- tyrosine -> tyrosine hydroxylase -> dopamine
- norepinephrine ->phenethanolamine -> epinephrine
- histidine -> histidine decarboxylase -> histamine
- tryptophan -> tryptophan-5-hydroxylase -> 5-hydroxytryptophan -> acid decarbxylase -> serotonin
