Term
| How are neurotransmitters released? |
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Definition
| neurotransmitters are packaged into vesicles & released as quanta |
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Term
| Why did people consider the hypothesis that neurotransmitters are released through a channel? |
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Definition
| ACh is a positive ion...people thought ACh would go through an ACh channel & outside of the cell; thought calcium would enter into the cell, attach to an intracellular receptor on the ACh channel, then open the channel for ACh to move out |
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Term
| is neurotransmitter released through a channel: results of experiments testing that movement of ACh would change the voltage (because it is a positive ion) |
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Definition
| they recorded from the presynaptic neuron & looked for when mEPPs occurred to see if there was a change in membrane potential...there was not! |
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Term
| is neurotransmitter released through a channel: results of experiments testing driving force is dependent on membrane potential |
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Definition
| experiments shows that changing presynaptic membrane had no effect on postsynaptic mEPPs |
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Term
| is neurotransmitter released through a channel: results of experiments testing quantity of ACh dependent on ACh concentration gradient |
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Definition
| introduced acetocholinesterase which should delete ACh & decrease mEPPs...again, this did not happen |
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Term
| is neurotransmitter released through a channel: results of experiments testing should be able to record an ACh channel current |
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Definition
| no change in presynaptic current |
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Term
| conclusion of experiments testing if neurotransmitter is released through a channel |
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Definition
| ACh channels existing & being important for neurotransmitter release was refuted |
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Term
| big breakthrough in imaging evidence for vesicular release |
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Definition
| the use of the electron microscope |
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Term
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Definition
| you can separate a synapse (like peeling apart the presynaptic side from the postsynaptic side |
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Term
| Why don't you see vesicular release using electron microscopy/flash-freeze fracturing? |
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Definition
| cell dies in the phase of fixing it |
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Term
| ______ can "store charge" |
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Definition
|
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Term
| 2 ways capacitors increase capacitance |
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Definition
1. bigger surface area
2. thinner space between plates (smaller dielectric) |
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Term
| Do neuron membranes work as good or bad capacitors? |
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Definition
|
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Term
| 3 ways to think of the neuron as a circuit |
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Definition
1. membrane is like the capacitor
2. resting membrane potential is like the battery
3. ion channels are like the resistors |
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Term
| Why does adding the omega figure to the membrane increase its capacitance? |
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Definition
| it is like increasing the surface area of the membrane |
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Term
| What cells were used to study capacitance as a measure of vesicle fusion? |
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Definition
| mast cell that releases very large vesicles |
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Term
| Increase of capacitance indicates what in terms of vesicular release? |
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Definition
| fusion of vesicle membrane to plasma membrane of the cell (exocytosis) |
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Term
| Decrease of capacitance indicates what in terms of vesicular release? |
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Definition
|
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Term
| What did experiments prove in terms of vesicular release? |
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Definition
| you really are adding plasma membrane to the cell |
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|
Term
| Capacitance is measured in ______ |
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Definition
|
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Term
| Testing of what theory led to the discover of synapsin? |
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Definition
| they knew calcium needed to come into the terminal to cause a release --> hypothesis that calcium phosphorylated proteins to allow this to happen |
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Term
| control situation of presynaptic cell stimulation |
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Definition
| get an EPSP after stimulation |
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Term
| result of stimulation after input of phosphorylated synapsin into electrode |
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Definition
| no change from the control situation --> phosphorylated version of synapsin isn't important to vesicle release |
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|
Term
| result of stimulation after input of just synapsin (dephosphorylated) |
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Definition
| much smaller EPSP from control --> dephosphorylated synapsin inhibited vesicular release |
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Term
| result of stimulation after input of CaMKII (cam kinase two...calcium kinase) |
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Definition
| much larger EPSP from control --> phosphorylated the synapsin that's already in the terminal |
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Term
| conclusion of experiments testing synapsin phosphorylation state |
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Definition
| synapsin regulates the availability of vesicles for release |
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|
Term
| RRP (readily releasable pool) |
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Definition
| the vesicles that are sitting right on the membrane; "docked vesicles" |
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Term
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Definition
| not what is released immediately, but feeds into RRP |
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Term
| The reserve pool contains about _______% of vesicles in the presynaptic neuron |
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Definition
|
|
Term
| What shuttles vesicles back & forth between the different pools? |
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Definition
|
|
Term
| ______ plays a really key role in vesicle trafficking |
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Definition
|
|
Term
| Is there a consistent amount of vesicles in a presynaptic terminal? |
|
Definition
| no! varies depending on type of cell/part of brain/body |
|
|
Term
|
Definition
1. actin
2. presynaptic vesicles |
|
|
Term
| Are synaptic vesicles covered by a lot or very few proteins? |
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Definition
|
|
Term
|
Definition
1. VAMP (synaptobrevin)
2. Rab-3
3. synaptotagmin |
|
|
Term
| 4 synaptic membrane proteins |
|
Definition
1. SNAP25
2. syntaxin
3. nSec1 (Munc18)
4. calcium channel |
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|
Term
|
Definition
1. cytoskeleton
2. exocyst |
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|
Term
| 2 proteins that tether vesicle to presynaptic membrane |
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Definition
|
|
Term
| ______ sits on syntaxin as a blocker |
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Definition
|
|
Term
| Where does the calcium channel sit? |
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Definition
|
|
Term
| _______ sits on vesicle & has calcium binding sites |
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Definition
|
|
Term
|
Definition
|
|
Term
| You need ______ calcium ions to bind for vesicle release |
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Definition
|
|
Term
| Calcium ions bind via ______ binding |
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Definition
|
|
Term
| 6 steps in vesicle fusion |
|
Definition
1. transportation
2. prior to docking
3. docked
4. primed
5. depolarization causes calcium entry
6. fusion |
|
|
Term
| 2 parts in transportation step of vesicle fusion |
|
Definition
1. cytoskeleton holds vesicles until they're ready to go
2. exocyst shuttles vesicles to the plasma membrane |
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|
Term
| Prior to docking, ______ temporarily tethers vesicle to membrane |
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Definition
|
|
Term
| ______ goes away so syntaxin is able to tether so the vesicle can dock |
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Definition
|
|
Term
| 3 things that associate to dock the vesicle so that it is primed |
|
Definition
1. SNAP25
2. syntaxin
3. VAMP |
|
|
Term
| Calcium entry due to depolarization --> ______? |
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Definition
| calcium comes in & binds to synaptotagmin to release it & the CORE complex |
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|
Term
| Synaptotagmin gets released due to _______ |
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Definition
|
|
Term
| What step of vesicle release includes synapsin? |
|
Definition
|
|
Term
|
Definition
1. SNAP25
2. syntaxin
3. VAMP |
|
|
Term
| ______ acts as a clamp to hold proteins all together waiting for the calcium |
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Definition
|
|
Term
| _______ must bind to synaptotagmin for fusion to happen |
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Definition
|
|
Term
| another name for synaptobrevin |
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Definition
|
|
Term
| Synaptotagmin has ______ calcium binding domains |
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Definition
|
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Term
|
Definition
| calcium domains pulling on the membrane |
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|
Term
| fusion pore transition state |
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Definition
|
|
Term
| _______ must be overcome for membranes to fuse |
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Definition
|
|
Term
|
Definition
| laser beam comes through microscope & where the laser beam focuses attracts colloidal particles & will hold the particle in place |
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Term
| Why did scientists use the optical tweezer? |
|
Definition
| to measure the force required (in pico-newtons) to break binding between synaptic membrane & vesicle membrane |
|
|
Term
|
Definition
| discovering if certain proteins will bind go other proteins |
|
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Term
|
Definition
| generate protein fragments that mimic the binding site of one protein & this will block the one protein from binding to the other protein |
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|
Term
| mutations & knock-out experiments |
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Definition
| once you've learned that a protein is critical, you wanna find out which part of the protein is actually important |
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Term
|
Definition
| cleave proteins at very specific points & can see the effect |
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|
Term
| The ______ site on the calcium channel competes off binding of calcium channels with syntaxin |
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Definition
|
|
Term
| peptide fragment experiment testing the synprint peptides competing off calcium channel binding |
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Definition
| put peptides into the presynaptic neuron & record voltage from presynaptic neuron...the peptides end up binding on the syntaxin so the calcium channels can't associate how they normally do --> much decreased EPSP |
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|
Term
| How can you regain the original EPSP in the presence of synprint peptides? |
|
Definition
| if you increase calcium in the extracellular fluid |
|
|
Term
| nSec1 being on syntaxin --> ? |
|
Definition
| syntaxin is bent & cannot work with the other SNARE proteins |
|
|
Term
|
Definition
| abnormal neurotransmitter release (slow release with repeated stimulation) |
|
|
Term
| mutating nSec1 so it cannot interact with Rab-3 --> ? |
|
Definition
| you cannot get vesicle release |
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|
Term
| The _____ domain of synaptotagmin is highly conserved |
|
Definition
|
|
Term
| The _______ of synaptotagmin is where it embeds into vesicular membrane |
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Definition
|
|
Term
| difference between C2A & C2B on synaptotagmin |
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Definition
C2A: binds 3 calcium
C2B: binds 2 calcium |
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|
Term
| took out synaptotagmin molecule (deleted from genome) --> ? |
|
Definition
|
|
Term
| difference in response of cells with/without synaptotagmin |
|
Definition
control (with synaptotagmin): get an EPSC
knock-out cells: get vesicular release but not smooth because they are a series of non-coherent minis |
|
|
Term
| 2 reasons you can get any release despite lack of synaptotagmin |
|
Definition
1. DOC2 protein causes vesicular release but not nice & smooth like synaptotagmin
2. brain & body are very adaptable to knock-out genes (compensate for lack of synaptotagmin) |
|
|
Term
| deleting an amino acid in the C2B domain --> ? |
|
Definition
| less vesicle release at normal calcium levels |
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|
Term
| loss of entire C2B domain --> ? |
|
Definition
|
|
Term
| taken out synaptotagmin entirely --> ? |
|
Definition
|
|
Term
| How does the human mutation in synaptotagmin C2B domain cause LEMS-like pre-synaptic NMJ dysfunction? |
|
Definition
| synaptic release gets better over time with exercise due to calcium accumulating in presynaptic terminal |
|
|
Term
| Honey can breed the ______ disease |
|
Definition
|
|
Term
| 3 things associated with botulism |
|
Definition
1. canned food
2. honey
3. home canning |
|
|
Term
| 2 things affected by botulism |
|
Definition
1. NMJ
2. vesicular release |
|
|
Term
| Can botulism be used clinically/cosmetically? |
|
Definition
|
|
Term
| Why do people who get Botox have to keep going back? |
|
Definition
| the proteins cleaved will regrow eventually |
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|
Term
| Botox can be used to treat ______ |
|
Definition
|
|
Term
|
Definition
| a toxin made under anaerobic conditions (like botulism) |
|
|
Term
| Why is tetanus so deadly? |
|
Definition
| once it's in, it will cross transynaptically to the CNS |
|
|
Term
| What protein is affected by tetanus? |
|
Definition
|
|
Term
| Is there a vaccine for tetanus? |
|
Definition
| yes! expires after about 10 years |
|
|
Term
|
Definition
| lockjaw (characteristic symptoms of tetanus) |
|
|
Term
| Why is botulinum toxin H so deadly? |
|
Definition
| it can kill hella people really fast |
|
|
Term
| Why was the discovery of botulinum toxin H not originally published? |
|
Definition
| they were scared of bioterrorism |
|
|
Term
| What strain of botulinum is the most similar to botulinum H? |
|
Definition
| botulinum A (so those antibodies worked for it) |
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