21 – The Nervous System I: Synapses Flashcards
Na+ ions
Na+ ions diffuse outward trigger neighboring Na+ channels open
Inactivation of V-gated Na+ channels by channel inactivation segment
plug the sodium in the shortly opened Na channel
gives directionality of action potential
Depolarization of axon terminal
trigger neurotransmitter release
Signaling in brain depend on…, therefore neurotransmitters…
…diffusion
Neurotransmitter diffuse across synaptic cleft
why is synaptic cleft so narrow
If we want that diffusion to be fast & effective at triggering the post synaptic cell
need to keep the distance very small which is why the synaptic cleft is narrow
why are Neurotransmitters small chemical compounds
Molecules that do the diffusing very small, because their diffusion coefficient depends upon their size and small, species diffuse much faster than large species,
Neurotransmitters packaged in…. by…
in synaptic vesicle by H+ gradient
as action potential reaches the Axon terminal, there will be
opening of voltage gated calcium channels & Influx of Ca2+ that triggers the release of the neurotransmitters & exocytosis of synaptic vesicles.
Binding of neurotransmitters
example:
depolarization of target cell
Specifically binding of acetylcholine
Neuroreceptors 2
o Ligand-gated
-neurotransmitter simply binds to the channel, causing it to open.
o GPCR
how you actually get neurotransmitters to be present in a high concentration inside of a vesicle.
the class of molecule that does the packaging: and what does it do?
V-class H+ pump
-Use energy of ATP hydrolysis to push proton up their chemical gradient
Neurotransmitters packaged in synaptic vesicles by H+ gradient
V-class H+ pump acidify the inside of the synaptic vesicle, pushing protons in
on other side of the synaptic vesicle = proton neurotransmitter Anti Porter A:
Molecule that takes a proton and lets it flow out while at the same time taking a neurotransmitter and making it flow In
In order for synaptic transmission to be Fast:
need synaptic vesicles to be ready to fuse with the membrane and undergo endocytosis as fast as possible after the action potential reaches the synaptic cleft.
-Synaptic vesicles docked directly on the membrane of the pre synaptic cell by SNARE complexes
–No time to wait for Ca2+ to flow in
what is SNARE complexes
bundles of actin helices that hold 2 plasma membrane in close proximity
by holding synaptic vesicle very close=enabling it to rapidly fuse.
snare complexes are target of a well known botulinum toxin - major component of BOTOX
how does BOTOX work?
BOTOX undocks synaptic vesicles & prevents acetylcholine release
Target SNARE complex & degrade them
when the your brain sends a signal to contract your facial muscles, those synaptic vesicles cant fuse with the PM= they cant release their neurotransmitter = unable to contract the muscles.
which is what then causes all of your facial muscle muscles to relax.
Which is then what reduces wrinkles because there’s just a general relaxation of all of the of the facial muscles
influx of calcium as the Axon terminal depolarizes is going to have to affect snare complexes: Ca2+ influx does what?
Ca2+ binds to Synaptotagmin-displaces Complexin = membrane fusion & neurotransmitter release
what is the Ca2+ sensor?
Synaptotagmin
Trigger fusion of synaptic vesicles occur by …
“kiss & run” mechanism
=fuse briefly & retract back up
Na+ symporters
reuptake of neurotransmitters
-Use free energy of Na+ moving down its concentration gradient into the cell
-Couples the -∆G with +∆G of moving neurotransmitter back into the cell
the pulling back up of that synaptic.
vesicle after it’s partial or complete fusion relies on:
Recycling synaptic vesicles require
GTPase Dynamin
-Relies on GTPase
-Partial/complete fusion by Dynamin
-Oligomerize into a coil/helix around neck of vesicles: in response to GTP binding, Helix has a change in its pitch that causes it to squeeze the vesicle and pinches it off.
Dynamin -Shibire mutation & the flies recovery.
Mutation in Dynamin in fruit flies - paralyzed
Ability to recycle synaptic vesicles slowly decreases when temperature increases = paralyzed
ability to recycle their synaptic vesicles is going to slowly go away.
recovery:
-protein domains refold
-The dynamin becomes active again.
-The neurons begin recycling their synaptic vesicles.
-The dynein becomes function.
-pull the synaptic vesicles back up&slowly refill synaptic vesicles and now flies are healthy again.
reason that you have so many synaptic vesicles in synaptic Cleft
Only 10% of vesicles are docked at a memebrane at a given time
-to Allow your cells to do multiple repeated rounds of firing.
allow the neuron to accomplish multiple firings while in the process of rebuilding its synaptic vesicles.
full vesicle cycle summary:
- import of neurotransmitter by the V class H Pump
- Use of H+ gradient to drive the import of neurotransmitter into the vesicles.
- move those vesicles Down towards the synaptic Cleft & docked by Snare complexes( target of the botulinum toxin.
- Calcium influx Causes synaptotagmin to bind calcium.
- synaptotagmin displaces complexin, the snares do their snapping = conformational change.
- The vesicle fuses = release of neurotransmitter into the synaptic cleft
- formation of a coat and a dynamin at bottom, pulling vesicle back up into the Axon terminal.
- Reuptake of neurotransmitters accomplished by Na symporters.
9.Recover and refill of uncoated vesicle and prepare for another round.
