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Block 3: Unit 1
Ionotropic Receptors
71
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Undergraduate 4
11/08/2016

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Term
A neurotransmitter is inhibitory or excitatory depending on ______
Definition
the type of receptor to which it binds
Term
Can a given neurotransmitter have different effects?
Definition
yes! (because it can bind to different kinds of receptors)
Term
Do some receptors have channels?
Definition
yes! (so people use the terms interchangeably sometimes)
Term
What is another name for ionotropic channels?
Definition
ligand-gated channels
Term
Can metabotropic receptors bind a neurotransmitter like ionotropic channels?
Definition
yes! (sometimes can work with the same ones such as ACh)
Term
Can you have ionotropic or metabotropic receptors that are presynaptic too?
Definition
yes!
Term
Do ionotropic or metabotropic receptors tend to be much closer to where neurotransmitter is released?
Definition
ionotropic
Term
Do ionotropic or metabotropic receptors tend to be more outside of the synaptic cleft?
Definition
metabotropic
Term
Difference between ionotropic vs metabotropic receptors: speed of effects
Definition
ionotropic = rapid effects

metabotropic = slow effects
Term
Difference between ionotropic vs metabotropic receptors: speed of termination of effects
Definition
ionotropic = rapid termination of effects

metabotropic = slow termination of effects
Term
Difference between ionotropic vs metabotropic receptors: relationship between action & response
Definition
ionotropic = 1:1 relationship between action & response

metabotropic = >1:1 amplification of response
Term
Difference between ionotropic vs metabotropic receptors: range of effects
Definition
ionotropic = range of effects limited by receptor

metabotropic = diverse possible effects from a single transmitter
Term
What does nAChR stand for?
Definition
"nicotinic acetylcholine receptors"
Term
______ is also a ligand for the nAChR family of ACh receptors
Definition
nicotine
Term
Why do scientists use the torpedo fish that kill their prey by stunning them to study nAChRs?
Definition
underside has tons & tons of ACh receptors...super dense --> allows scientists to really study these receptors (easier to purify for them because they're so dense)
Term
In nAChRs, the ACh binding site is ______
Definition
extracellular
Term
nAChRs have a "gate" that ______ when ligand binds
Definition
opens
Term
2 different main types of nAChRs
Definition
1. nicotinic receptors found on muscles
2. nicotinic receptors found on neurons
Term
Is the extracellular domain where neurotransmitter binds on muscle nAChRs complicated or simple?
Definition
complicated
Term
Is the intracellular domain of muscle nAChRs as complicated as the extracellular domain?
Definition
no!
Term
2 ions mainly passed by muscle nAChRs
Definition
1. sodium
2. potassium
Term
The resting membrane potential of muscle nAChRs is reliant on both _____ & ______
Definition
sodium & potassium (but it isn't quite the average between the two because there is unequal conductance for each ion)
Term
4 different types of subunits of muscle nAChRs
Definition
1. two alpha
2. one beta
3. one delta
4. one gamma
Term
Muscle nAChRs require at least two ______ subunits
Definition
alpha
Term
different subunit makeup of muscle nAChRs --> ?
Definition
different functions of the proteins
Term
Each neuronal nAChR has ______ TMRs
Definition
4
Term
______ is the domain that forms inside of the pore of neuronal nAChRs
Definition
M2
Term
homomeric neuronal nAChRs
Definition
all five subunits are the same
Term
heteromeric neuronal nAChRs
Definition
not all five subunits are the same
Term
Difference in nomenclature between neuronal nAChR subunits & domains
Definition
subunits = the ones with the Greek letters

domains = M1 - M4 (within each subunit)
Term
What are you looking for when you look at a dissociation constant graph for muscle & neuronal nAChRs?
Definition
graph looking at how much concentration you need of ACh to bind 50% of your receptors
Term
Why do muscle nAChRs need a higher concentration of ACh than neuronal nAChRs to activate muscle?
Definition
they have a lower affinity
Term
Will neuronal nAChRs have a higher or lower dissociation constant than muscle?
Definition
lower
Term
agonist
Definition
a compound that elicits the same biological effect(s) as the natural ligand when it binds to a receptor
Term
antagonist
Definition
a compound that attenuates the effect of an agonist when bound to a receptor
Term
competitive antagonist
Definition
binds to the same site as the agonist, but does not activate the receptor
Term
non-competitive antagonist
Definition
binds to the receptor at a different site from the agonist, but prevents activation of the receptor
Term
reversible antagonist
Definition
binds non-covalently to the receptor, so can come off the receptor by "washing off"
Term
irreversible antagonist
Definition
binds covalently to the receptor, so cannot be displaced by either competing ligands or "washing off"
Term
What does it mean that the binding of a ligand is probabilistic?
Definition
the binding frequency depends on the concentration of the ligand
Term
4 main symptoms of the myasthenia gravis disease
Definition
1. compromises specific groups of striated muscle
2. oculomotor disturbances & oropharyngeal muscle weakness (limb weakness in about 10% of patients)
3. course of the disease is variable, but generally progressive
4. severity of symptoms fluctuates throughout the day (strength decreases with exercise)
Term
What is the most common primary disorder of the neuromuscular junction?
Definition
myasthenia gravis
Term
What type of disease is myasthenia gravis?
Definition
an autoimmune disease of the NMJ
Term
3 main treatments for myasthenia gravis disease
Definition
1. cholinesterase inhibitors (the goal is to increase the amount of transmitter in the cleft)
2. Thymectomy (long term treatment to reduce production of anti-ACh receptor antibodies)
3. plasma exchange (short term treatment to reduce antibodies for those who have a sudden worsening of symptoms or to improve recovery from other procedures such as surgery)
Term
difference between non-NMDA & NMDA ionotropic glutamate receptors: agonist
Definition
non-NMDA = AMPA & kainate

NMDA = NMDA
Term
difference between non-NMDA & NMDA ionotropic glutamate receptors: conductance
Definition
non-NMDA = low conductance

NMDA = high conductance
Term
difference between non-NMDA & NMDA ionotropic glutamate receptors: ion permeability
Definition
non-NMDA = sodium, potassium (some calcium)

NMDA = sodium, potassium, calcium
Term
difference between non-NMDA & NMDA ionotropic glutamate receptors: gating speed
Definition
non-NMDA = fast gating speed (like voltage-gated)

NMDA = slow gating speed
Term
difference between non-NMDA & NMDA ionotropic glutamate receptors: magnesium block
Definition
non-NMDA = no magnesium block

NMDA = magnesium block
Term
classes of ionotropic glutamate receptors are differentiated by ______
Definition
the type of ligand they bind
Term
In order for NMDA channel to have current, ______ must be present & bind (no matter what!)
Definition
glutamate
Term
______ can bind to a site inside of the NMDA channel & block the channel
Definition
magnesium
Term
How does magnesium get pushed out of the NMDA pocket?
Definition
once membrane potential depolarizes pretty high (~ -20)
Term
Differences in the IV plot of NMDA receptors based on if magnesium is present or not
Definition
if there is no magnesium present = you get basically a normal linear IV plot

if magnesium is present = at hyperpolarized potentials there is virtually no current; once you reach a sufficient membrane potential, the current becomes pretty linear & normal looking
Term
coincidence detector for NMDA receptors
Definition
you need both glutamate present/bound & a depolarized enough membrane potential
Term
______ that flows through NMDA receptor channels is a big deal
Definition
calcium
Term
excitotoxicity
Definition
cells get too excited & cell dies
Term
Ionotropic GABA & glycine receptors have mostly ______ reactions
Definition
inhibitory
Term
Both GABA & glycine receptors have ______ subunits
Definition
5
Term
______ receptors have a glycine binding site & pass chloride
Definition
glycine
Term
2 main categories of GABA receptors
Definition
1. GABA "A" (the ionotropic ones)
2. GABA "B" (the metabotropic ones)
Term
BZs
Definition
drugs that act on GABA "A"; bind to a different site than where GABA binds

*you need GABA to trigger opening even if BZ is bound*
Term
GABA receptors pass _____ in
Definition
chloride
Term
Cell resting at a more positive membrane potential than chloride equilibrium potential: influx of chloride will cause _____
Definition
IPSP
Term
Why can you really see the difference of the effect of chloride influx at various resting membrane potentials?
Definition
chloride reversal potential is about equal to the resting membrane potential
Term
Cell resting at a more negative membrane potential than chloride equilibrium potential: influx of chloride will cause _____
Definition
EPSP
Term
"Blunting" inhibition
Definition
chloride having an effect on resting membrane potential draws membrane potential down lower than when just sodium & potassium were in play
Term
shunting inhibition
Definition
1. having chloride channels increases conductance (reduces resistance)

2. if current is the same, then voltage has to go down (V = I*R)

3. results in a smaller EPSP
Term
GABA "A" receptors are hyperpolarizing if Ecl ? Vrest
Definition
Ecl < Vrest
Term
GABA "A" receptors have a shunting effect if Ecl ? Vrest
Definition
Vrest < Ecl < action potential threshold
Term
GABA "A" receptors have an excitatory effect if Ecl ? action potential threshold
Definition
Ecl > action potential threshold
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