Neurobio Exam 2 Flashcards
How does information transfer occur at chemical synapses?
Electrical depolarization of the nerve terminal causes the release of chemicals that open postsynaptic ligand-gated ion channels which pass current, depolarizing the postsynaptic cell.
Dendritic spines are commonly a site for
excitatory synaptic transmission.
How does acetycholinesterase function at synapses that release acetylcholine?
It is a synaptic cleft enzyme that breaks down the transmitter acetylcholine.
How do transmitters act on the postsynaptic cell at direct chemical synapses?
They bind to ligand-gated ion channels to induce postsynaptic current flux.
Synaptic vesicles are concentrated in large numbers within nerve terminals. What is their function?
They store and release chemical transmitter molecules.
Why does the plant alkaloid nicotine cause skeletal muscle contraction?
Nicotine is an agonist at postsynaptic nicotinic acetylcholine receptors.
How does the technique called ionophoresis work?
Molecules inside a glass pipet can be expelled by electrical charge.
Molecules inside a glass pipet can be expelled by electrical charge.
They are highly concentrated directly under the presynaptic terminal at the NMJ.
What is the reversal potential for a channel?
The membrane potential at which the net current flux through a channel is zero, and on either side of which the net current flux moves in opposite directions
What is the principal excitatory transmitter in the CNS?
Glutamate
When comparing direct and indirect synaptic transmission, indirect synaptic transmission
is mediated by metabotropic receptors that activate intracellular second-messenger pathways
The G proteins that are coupled to metabotropic receptors are
heterotrimeric GTP binding proteins made up of α-, β-, and γ-subunits.
For G protein-coupled metabotropic receptors, GTP binds to the
α-subunit of the heterotrimer.
How is G protein-mediated signaling terminated?
Hydrolysis of GTP to GDP by the endogenous GTPase activity of the α-subunit leads to reassociation of the αβγ-complex, terminating the response.
The particular neurotransmitter present at a synapse
does not indicate the subtype of G protein or second messenger that will be coupled to the receptor
What would happen to metabotropic signaling in a cell if you added GTP-γ-s to the cell cytoplasm?
This would irreversibly activate all G protein-coupled metabotropic signaling.
What happens when PIP2 is cleaved by PLC?
This cleavage generates inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) that act as second messengers.
How many transmembrane domains do all G protein-coupled metabotropic receptors have?
All G protein-coupled metabotropic receptors has 7 transmembrane domains
Which of the following neurotransmitters is not stored in synaptic vesicles?
Endocannabinoids
The particular neurotransmitter present at a synapse
does not indicate the subtype of G protein or second messenger that will be coupled to the receptor.
What explains why there is a threshold depolarization of about 45 mV above resting membrane potential before any transmitter release occurs?
This is the magnitude of depolarization required to activate presynaptic voltage-gated calcium channels.
Which is both necessary and sufficient to trigger chemical transmitter release from a presynaptic nerve terminal?
An increase in presynaptic calcium concentration
If one would like to use the voltage clamp technique to record presynaptic calcium currents from a nerve terminal, why are tetrodotoxin (TTX) and tetraethylammonium (TEA) used?
TTX blocks sodium channels and TEA blocks potassium channels.
What is thought to significantly restrict the spread of calcium ions after they enter the nerve terminal through presynaptic calcium channels?
Calcium buffers and binding proteins (chelators)
What is the definition of a quantum of transmitter?
A multimolecular packet containing about 7000 transmitter molecules
What is the calcium sensor for synaptic vesicle exocytosis?
Synaptotagmin
What is kiss-and-run exocytosis?
Vesicle pore formation with the plasma membrane that is not followed by full vesicle fusion, but rather by closure of the pore
What is the synaptic delay at a synapse that uses chemical transmitters at room temperature?
0.5 miliseconds
What is a nanodomain of presynaptic calcium ions?
The collected intracellular calcium ions that form around the mouth of a single open calcium channel
What is the difference between an electrical synapse and a chemical synapse?
The electrical synapse sends current through connexons and the chemical synapse sends current through the synapctic cleft that is bridged through the release of NTs
What are two ways chemical transmission is possible?
through metabotropic receptors and ionotropic receptors
what are metabotropic receptors?
Also known as g-protein coupled receptors (GPCRs)
They are receptors about to g-proteins
they are composed of alpha, beta, and gamma subunits
what does the alpha do when it binds to a g-protein on a GPCR?
it exchanges GDP for GTP
what does the GCPR do at resting state?
it sits on the membrane and is coupled to a G protein with an alpha subunit bound to it
what activates a GPCR?
an agonist
what happens after a GPCR is activated?
the alpha doesn’t want GDP anymore and instead wants to bind to GTP
so the alpha subunit and the gamma-beta subunit disassociate and leave separatly to target protein
how does the GPCR cycle resets?
with GDP gone, the receptor needs alpha back to reset
How are the different G proteins classified?
through the different actions the do
what ultimately decides what classification of action happens when a GPCR is activated?
what G-protein the alpha subunit is able to bind to
What are the 4 G-proteins we talked about?
Gi, Go, Gs, Gq
What G-protein activates PIP?
Gq
What is the PI cycle?
Explain the mechanism of Gi protein when it is activated
causes inhibition through opening of K+ channels
It inhibits the Adenylate cyclase which in turn inhibits cyclic AMP which in turn excites potassium channels to open which in turn causes inhibition of the cell
the beta-gamma subunit binds directly to K+ channels and opens them.
Explain the mechanism of Go protein when it binds to the alpha subunit
it is neuron specific and acts on the presynapse
it binds to calcium channels to inhibit them, creating auto-inhibition to stop NTs release
it inhibits Ca channels (Cav2) which stops NTs release
The use of a chemical signal that communicates from the presynaptic cell back onto the same presynaptic cell is called
feedback inhibition
Explain the mechanism of Gs protein when it is activated
The alpha-subunit of Gs binds and activates adenylate cyclase which converts ATP into cyclic AMP which in turn acts as a second messenger to activate Kinase A which increases the phosphrylation of calcium channels, increasing their probability of opening, ultimately exciting the cell by releasing NTs
what is Kinase A protein
it depends on cAMP to activate and mediates the transfer of phosphate (from ATP) to a variety of enzymes and channels
what do Gi and Go proteins have in common?
they inhibit the cell it acts on
What is cyclic AMP (cAMP)?
work as second messengers
- works on Gs, Gq and Gi
what is Adenylyl cyclase?
an enzyme that converts ATP to cAMP
Explain the mechanism of Gq protein when it is activated
Gq activates phospholipase C which catalyzes the hydrolysis of PIP2 which produces 2 second messangers
- IP3 which leaves to release calcium ions from ER and contributes to various Calcium dependent processes
-DAG remains in the membrane and activates protein kinase C which phosphorylates calcium channels to increase chances of opening them
what channel does PIP2 regulate?
M-channels
what are M-channels
voltage gated K+ channel that regulate the excitability of many central and peripheral neurons
give an example of Go protein activity
Norepinephrine is released from neuron and it combines with the a2 receptor (an autoreceptor) which activated the Go protein
the gamma-bata subunits bind to calcium channels and inhibits them by decreasing calcium influx
what is rectification?
ions flow back to membrane potential (membrane allows outward current to flow more easily than inward current)
what is special about the cannabinoid receptor?
the 2ag receptor can auto-inhibit and also inhibit inhibition
describe some qualities of calcium
- is everywhere and does a variety of things
- presents differently at different concentration
- intercellular concentration is low (~10x lower than extracellular concentration)
- can be brought in through a bunch of different ways and channels
- can be ionotropic and metabotropic
- allows for NTs to release at synapses
what are the 4 processes of vessicular recycling pathways?
What is the kiss and run method?
walk through what happens at a synapse
what are 2 differences between metabotropic receptors and ionotropic receptors?
metabotropic receptors act through second messangers and work through g-proteins, also the work on a slower time frame
ionotropic receptors are ligand bound and act quickly
describe 4 features of chemical synapses that allows them to have more specialization than electrical synapses
they can be either excitatory or inhibitory and can be activated through direct or indirect transmission
what is reversal potential?
the voltage where the amount of sodium flowing in is equal to the amount of potassium flowing out
-similar to equilibrium potential
what do indirectly coupled protein act through?
g-proteins
how does glycine act as an inhibitor?
it makes Cl hyperpolarize signal which makes it harder to depolarize the cell and create an action potential
why are GPCRs important?
they’re practically everywhere and commonly found in neurons
important to study medicine
why are GPCRs a large part of studies in the medical field?
~1/3 of drugs bind to GPCRs
how many domains is a GPCR made of and why is that important?
7 domains, the odd number means that one end will be on the outside while the other will be on the inside
what is the end terminus do on GPCRs?
it forms the binding domain
what binds the G-protein on the GPCRs?
the intercellular loops
what does the tail do on GPCRs?
it can tune the phosphorylation
what is GEF
gynosine exchange factor
the exchange factor can switch which form it bound on or off when it binds to a ligand
What happens when an agonist binds to a GPCR?
it activates GEF which exchanged GDP for GTP and alpha subunit and gamma-beta subunit disassociate
what would happen to metabotropic signaling in a cell if pertussis toxin is added?
it would irreversibly inhibit Gi and Go signaling
what causes GPCRs to desensitize?
phosphorilation of the C-terminus (prime binding site located on the alpha-subunit) of the receptor
what is the C-terminus on a GPCR?
the prime binding site located on the alpha-subunit
what permits reassociation of subunits to GPCRs?
the alpha subunit has intrinsic GTPase activity that results in the hydrolysis of GTP back to GDP
what terminates the activity of G proteins?
when the alpha subunit and the gamma-beta subunits reassociate
