Receptors Flashcards
receptors required for action potential
ligand gated and voltage gated ion channels
Neuronal action potentials, after ACh binds to ligand gated ion channel what happens next?
Voltage gated Na+ channel opens THEN a voltage gated Cl-channel opens
an action potential starts with a _________ gated ion channel
Ligand gated ion channels
leads to action potential, positive ions go into the cell
Excitatory
Hyperpolarization, negative ions into the cells
Inhibitory
ligand binds to a receptor and activates it
agonist
ligand binds to receptor and prevents it from activating
antagonist
antagonist that acts on the main binding site
orthosteric antagonist
antagonist that acts on an accessory binding site
allosteric antagonist
antagonist that physically obstructs ion channel
pore blocker
pentamer
cys-loop receptors
tetramer
ionotropic glutamate receptors
cys-loop receptors
nicotinic ACh receptors
glycine receptors
5HT-3 Receptors (serotonin)
GABA-A receptors
ionotropic glutamate receptors
NMDA receptors
Kianate receptors
AMPA receptors
inhibitory cys-loop receptors
Glycine
GABA- A
excitatory cys-loop receptors
Nicotinic ACh Receptors
5HT-3 (Serotonin) Receptors
named fro the loop made by a disulfide bond
cys-loop receptors
physical gate of cys-loop receptors
the second transmembrane domain of the ALPHA subunit
causes ALPHA subunit to change conformation
agonist binding
drugs that act on nAChR
Nicotine
Varenicline (Chantix)
drugs that act on GABA-a
Ambien (Zolpidem), Barbituates, Benzodiazepines, Alcohol
T/F drugs have distinct binding sites that allow it to effect receptors in a unique way
True
drugs that act on NMDA receptors
Ketamine
drugs that act on AMPA receptors
Aniracetam (cognition enhancer)
nAChR subunits at neuromuscular junction
alpha, beta, gamma, delta
subunits at neuronal nAChR
alpha and beta
Receptor that pass Na, K, Ca
Has non-selective cation channels
composed of five subunits
ion passage depends on subunits
nAChR
drug that causes an UPREGULATION of receptors in response to chronic presence of drug
Nicotine - this is why it is hard to quit smoking
ACh binds to _________ subunit
ALPHA
not passing ion but ligand is bound
receptor in desensitized state
receptor cannot be activated because a ligand is bound
receptor in desensitized state
state of receptor when no ligand is bound
closed
when ligand is bound and ions are actively passing receptor is
open
two things that effect the propensity of a receptor to fall into a desensitized state
- what agonist is bound to the receptor
2. the subunit composition of the receptor
AMPA, Kainate, NMDA
Ionotropic glutamate receptors
only inotropic glutamate receptor that can pass calcium
NMDA
the 2nd transmembrane domain forms the ion pore
ionotropic glutamate receptors
each subunit has a binding site, but they are not all for glutamate
ionotropic glutamate receptors
ALL 4 binding sites of these receptors MUST be occupied for the channel to open
ionotropic glutamate receptors
what needs to be bound for NMDA receptors to open?
2 Glutamate, 2 Glycicne
What needs to be bound for AMPA receptors to open?
4 Glutamates
Gage at which cell can understand how often it is working
NMDA receptor activity
_________ receptors are blocked by a _________ ion. This block is _________ dependent.
NMDA
Mg++
voltage
in long term potentiation how does the NMDA receptor open?
Depolarization of the neuron relieves the Mg+ block and the receptor can open to pass ions
in long term potentiation after the NMDA receptor opens what ions are passed?
Ca++ and Na++ come into the cell
What specifically leads to more AMPA receptors being inserted onto the synapse?
NMDA receptors pass calcium which ACTIVATES Ca MKII (calcium calmodulin kinase II)
in long term potentiation there is also a __________ messenger that goes back to the __________ terminal
Retrograde, pre-synaptic
what does having more AMPA receptors on the surface mean?
It is a stronger synapse
What signals to the intercellular AMPA receptors to be inserted onto the pre-synaptic terminal?
Calcium Calmodulin Kinase II
Coincidence Receptors
NMDA Receptors
In long term potentiation first the _______ receptors are activated which then depolarize the neuron and causes the _______ to be relieved and activate the _________ receptors which then allow a __________ influx activating ___________ to signal to the neuron to insert __________ receptors on the surface of the neuron.
AMPA Magnesium Pore Blocker NMDA Ca++ and Na+ Calcium calmodulin kinase II AMPA
GPCR Class A
Adrenergic receptors
Muscarininc ACh receptors
GPCR class B
Parathyroid hormone receptor
GPCR class C
Metabatropic Glutamate receptors
GABA-b Receptors
Excitatory
Activate Adenylyl Cyclase
increase cAMP
G alpa sub S Receptors
Inhibitory
Inhibit Adenylyl Cyclase
Decrease cAMP
G alpha sub I Receptors
Excitatory
Activates Phospholipase C
Increase in IP3
Release on Ca++ from intracellular stores
G alpha sub Q Receptors
What is a primary factor in GPCR Desensitization?
B-Arrestin
what causes B-arrestin to bind to the receptor?
A ligand bound to the GPCR for a prolonged period of time
When B-arrestin binds it…
Tags the GPCR for internalization
An internalized GPCR by B-Arrestin contributes to…
Drug tolerance
The GPCR-B-Arrestin complex is brought inside the cell via an _________.
Endosome
Three things that an endosome can do with the GPCR-B-Arrestin complex
- Degrade the complex
- cause an activation of signaling cascades from inside the cell that are INDEPENDENT of G Protein signaling
- Return the complex to the cell surface
Time it take for B-arrestin to bind to GPCR
Seconds to minutes
Time it takes B-Arrestin to internalize a GPCR
Minutes
What is GRK? What does it do?
GPCR Kinase.
It adds a phosphate to the G-protein inside the cytoplasm.
This phosphate is what attracts B-Arrestin
What to drugs that target the GRK (G protein coupled receptor kinase) do?
They can optimize agonist binding
What is the main reason for the downstream effects of the cholera toxin?
Cholera toxin does not allow GTP to become a GDP resulting in A GPCR that is permanently on
What is the GPCR that is permanently on when the cholera toxin is present and what are the downstream effects?
G alpha S - causes cAMP to increase dramatically.
This activates Cl- pumps which then release more Cl- into the intestinal lumen
Na+, K+ and HCO3- ions follow
H2O follows the ions to balance the osmolarity
Increased H20 in lumen = really bad diarrhea!
