Synaptic tranmission (Sept 18) Flashcards
What are the three modes of synaptic transmission?
Vesicular
Non-vesicular
Retrograde Release
What is Non-Vesicular ATP release?
It is release of neurotransmitter that is not in vesicles. (but is still not permeable to the membrane, so leaves through ion channels). An example of this is release of ATP in taste buds.
Do taste cells have a direct neurological connection to the brain? If they do not how do they transmit an action potential?
No, binding of tastant’s to taste receptors leads to cutting of peptidylinositol by phospholipases. Which causes IP3 and DAG, IP3 causes release of intracellular calcium, which causes an pseudo-action potentials with VGSCs that causes VG(ATP)Cs to open which releases ATP into the synapse firing the post synaptic cell to fire a potential.
Why do motor end plats each have 100 - 300 synaptic vesicles?
To guarantee that they will always fire a potential.
Where was quantal exocytosis first discovered? Why?
At the neuromuscular junction. Because the prep is very hardy and the channel very consistant.
EPSP stands for what/is what?
Excitatory Post-Synaptic Potential. Depolarization of the cell (Na channels)
IPSP stands for what/is what?
Inhibitory Post-Synaptic Potential. Hyper polarization (Cl channels open).
What is a miniature end-plate potential?
MEPPs, are small depolarizations which result from the release of a single vesicle of neurotransmitter. at the neuromuscular junction.
What is an EPP?
End plate potential. It is an EPSP at the neuromuscular junction (it’s called this because of motor end plates)
What is a miniature excitatory post synaptic potential?
MEPSPs, are small depolarizations which result from the release of a single vesicle of neurotransmitter.
What is a... Agonist: Antagonist: -Competitive -Non-Competitive Inverse Agonist:
Agonist: ligand which activates a receptor
Antagonist: stops the receptor it binds to from being activated.
-Competitive: competes for binding site
-Non-Competitive: binds elsewhere
Inverse Agonist: Binds to receptor which is always in its active conformation to deactivate it
What is constitutive activity?
Continuous never ceasing activity.
What are the four possible fates of neurotransmitters?
Diffusion: diffuse out of synaptic cleft
Degradation: Broken down by enzymes (like achetylchoninesterase in the neuromuscular synapse.
Re-uptake: returned to the pre-synaptic cell, via specialized membrane transporter proteins.
Uptake: taken in by surrounding glial cells, via specialized transporter proteins
What type of specialized protein enables reuptake and uptake?
Membrane transporter proteins.
Could a neurotransmitter be excitatory at one synapse and inhibitory at another? How is this possible.
Yes. The neurotransmitter could be binding to a different type of transmitter at the other cell, one which allows influx of different type of ion than in the other cell.
I have a neurotransmitter which is causing an inhibitory at this synapse by opening Cl channels, might it be able to perform an excitatory response at a different synapse, opening let’s say Na?
Yes, neurotransmitters are non specific. Instead the response of the cell (which is dictated the types of receptors) is what matters.
What is the purpose and location of K+ leak channel?
Maintain resting potential, all animal cells.
What is the purpose and location of voltage gated Na+ channel?
Action potential, nerve cells.
What is the purpose and location of voltage gated K+ channel?
Return membrane to resting potential.
Is GAMA normally excitatory or inhibitory?
inhibitory. but it must be a cl- channel.
Ionotropic membrane proteins must contain?
An integral ion channel.
What 3 molecules are listed in the small molecules class of neurotransmitters?
ACh
ATP
NO (nitric oxide) (fat soluble)
What 4 molecules are listed in the small amines class of neurotransmitters?
Dopamine.
Serotonin
Epinephrine
Norepinephrine
What 4 molecules are listed in the amino class of neurotransmitters? Probably just pick amino acids…
GABA (gamma-amino-butyric acid)
glycine
glutamate
aspartate
What 6 molecules are listed in the neuropeptides class of neurotransmitters?
Somatostatin beta-endorphin arginine Vasopressin Insulin Glucagon Calcitonin
What 3 molecules are listed in the lipids class of neurotransmitters?
Sphingosine-1-phosphate
Anandamide
2-arachidonylglycerol (2-AG)
What are the three criteria to be a neurotransmitter?
1, Localized to presynaptic terminal
2, Secreted upon nerve stimulation
3, Exogenous application of substance must cause same response as endogenous substance.
What is iontophoresis?
bringing of ions into a junction via electrical current induced by a wire battery system.
What was this used to study?
It was used to exogenously supply acetyl choline to muscle synapses.
Why is there a 1-2 ms delay between the arrival of an AP at the presynaptic terminal and a postsynaptic response? What is the time of this delay most affected by?
This is caused by the time it takes to exocytose vesicles, for protein protein interactions to occur, for channels to open and neurotransmitter to diffuse. It is temperature dependent.
Why is the Neuromuscular junction (NMJ) the most studied synapse in the world?
Because it is hardy, has a huge response, and is easily seen (large).
What is the neurotransmitter which is used in the NMJ? How much in excess?
Acetylcholine. 3X as much as is needed.
What does Ach act as?
Excitatory response, from an agonist, at both the ionotropic and metabotropic level.
Why is there often so much folding in the postsynaptic cell at a neuromuscular terminal? (or really any synapse)
To maximize the surface area on which the neurotransmitter can act.
nAChR is what? In addition is it ionotropic, or is it metabotropic.
Nicotine acetyl choline receptor. These receptors normally bind acetylcholine but can also bind nicotine. They are ionotropic.
mAChR is what? In addition is it ionotropic, or is it metabotropic.
Muscuranic acetylcholine receptor. Muscarine is a poison in mushrooms, it binds to all 5 types of mAChRs. These are metabotropic.
Differentiate between nAChR and mAChR.
nAChR: ionotropic, nicotine can bind to it.
mAChR: metabotropic, there are 5 types. Muscarine binds to it.
What does Muscarine bind to?
mAChRs
nAChR has how many protein subunits?
5 total. 2 alpha, 1 beta, 1 gamma, 1 delta.
nAChR requires how many ACh to bind to it to become active.
2
nAChR allows which ions through?
It allows all cations?
How does nAChR select for all cations and only cations?
It utilizes negative charges strategically placed on both the cytosolic and extracellular side of the poor. These negative charges draw in cations, and repulse anions. The pore is large enough not to be cation selective so it lets all though.
What is the sarcolemma?
It is a membrane which wraps around muscle fibers/cells.
Name the six channels involved in a NMJ synaptic transmission.
VGSCs presynaptic (AP) VGCaCs Presynaptic nAChR postsynaptic VGSC postsynaptic in sarcolemma. VGCaCs in the T tubules Ca release channels (ryanodine receptors)
What is a ryanodine receptor? What is it mechanically linked to?
RyR1 receptors are linked to VGCaCs in the T tubules.
How many presynaptic neurons may connect to a central nervous system cell?
Up to 10,000 connections. Which is ridiculous. They presynaptic nerve terminals will be concentrated on the dendrites and soma.
Where in a nerve cell does an action potential originate?
In the initial segment (the axon hillock)
suprathreshold vs subthreshold
Above threshold, below threshold.
What is a presynaptic terminal called in a Central nerve cell?
A bouton (bottons).
If a nerve cell has many buttons, is one likely to cause an AP in the post synaptic cell?
No, it would likely be subthreshold.
If a nerve cell has few buttons, is one likely to cause an AP in the post synaptic cell?
quite possibly yes, one would likely cause suprathreshold depolarization.
Are central synapses plastic?
yes.
Which neurotransmitter is most abundant in the vertebrate brain?
Glutamate.
Glutamate binds to two receptors in the synapse, what are their names?
NMDA
AMPA
Which receptor NMDA or AMPA will bind glutamate when the neurotransmitter is released into the synapse?
NMDA and AMPA will both bind it!
How do NMDA and AMPA work?
NMDA receptors are VGCaCs with a Mg2+ block within them. AMPA is a Na+ receptor. Binding of glutamate to both NMDA and AMPA opens their pore systems, but NMDA is still blocked by Mg2+. Luckily, depolarization of the cell do to AMPA causes the cell to become more positive, pushing Mg2+ out, and allowing Ca 2_ to enter the cell.
What does release of Ca2+ via NMDA receptors (due to the action potential from AMPA receptors) do?
Increase in calcium causes long term changes. Like an increase in the number of AMPA receptors (increased sensitivity of the nerve cell.)
How do NMDA and AMPA relate to long term potentiation?
Addition of AMPA receptors caused by the AMPA Na potential triggered Ca2+ release from NMDA results in increased response, this builds up over time and is called long term potentiation.
Long-term depression
AMPA receptors will be removed if they are not being used (additionally all proteins have a half life).
