Lec 15 Flashcards
Which of the 2 main types of glutamate ionotropic glutamate receptor is rarely permeable to Ca2+ ?
AMPA
Which of the 2 main types of glutamate ionotropic glutamate receptor is slower and highly permeant to Ca2+?
NMDA
Which of the 2 main types of glutamate ionotropic glutamate receptor mediates the great majority of fast excitatory transmission in the CNS?
AMPA
Which of the 2 main types of glutamate ionotropic glutamate receptor is important in neuronal plasticity?
NMDA
In either temporal or spatial summation, actions potentials from EPSPs are initiated in what region of the neuron?
axon hillock or initial segment
benzodiazepines and barbiturates affect which ligand channel?
GABAa
Which ligand receptor subunit has its M2 enter and exit the membrane region rather than passing through it?
glutamate
How many binding regions are located on a glutamate ionotropic receptor?
4
what 2 subunits can be reversed in a Nicotinic Ach receptor?
B and y.
Where are the binding regions for ACh located on a AChR?
on the alpha subunits
In a subunit within a ionotropic glutamate receptor , which transmembrane region (M1,M2,M3,or M4) is thought to enter and exit the membrane region rather than pass through?
M2 doesn’t pass through. (glutamate subunit = 3 passes)
How many binding regions are located on a glycine receptor ?
2 (a, B)
Defects in Glycine receptors can lead what disease?
startle disease (hyperekplexia)
What is defined as “an potential that is equal to the sum of multiple EPSP or IPSPs that are received at a postsynaptic NEURON at the same time in order to reach threshold and exhibit and action potential (or inhibit an AP in the case of IPSP)”
spatial summation
When studying ionotropic post synaptic glutamate receptors, if the postsynaptic membrane has a very low membrane potential which channel will open?
AMPA because it is independent of postsynaptic membrane potential NMDA will not for opposite reason.
In either Temporal or spatial summation, action potentials from EPSPs can only occur when the summed potential …
rises above the threshold.
EPSP’s are mediated by what type of anion or cation channels?
cation channels
EPPs (such as ACh release and binding to a postsynaptic membrane) are strongest at what location?
closer to the motor endplate or the presynaptic terminal.
How many TM regions are there in an ionotropic glutamate receptor?
4 subunits x 3TM per unit = 12 TM
Which of the 2 main types of glutamate ionotropic glutamate receptor is permeable to K+ and Na+ ?
AMPA and NMDA (both)
Oligopentamer channels/receptors came from a common ancestor . Over time, the structures split into two different catagories called:
Anion selective and Cation selective ligand gated channels
What drug will cause an increase in the Cl- conductance of an open GABAa channel ?
benzodiazepine
What type of ligand receptor contains binding region on its a only?
AChR
What are the 3 types of ionotropic glutamate receptors?
- AMPA-type subunits (GluR 1-4) 2. NMDA-type subunits (NMDAR 1, 2A-2D) 3. Kiante-type subunits (GluR 5&6 and KA1&2)
How many AMPA-type subunits are there in a glutamate ionotropic receptor?
4
What is the radial spacing of the subunits on an AChR? (in degrees)
72º
What are the 2 more important ligand gated anion channels?
Glycine and GABAa
GABAa channels can have their inhibitory effects increased by the addition of what substances?
barbiturates or benzodiazepines
How many subunits are in a glutamate ionotropic receptor?
4
What are the AMPA-type subunits in a glutamate ionotropic receptor?
GluR1, GluR2, GluR3, GluR4
at a NMJ or motor end plate, How is it possible to determine the selectivity or type of channel present on the postsynaptic membrane?
by voltage clamping the postsynaptic membrane and treating it with curare to create subthreshold responses and prevent APs, and recording the voltage-current relationship. By locating the reversal potential or nernst potential (where I=0), we an distinguish what type of channel is present.
What substance blocks GlyR?
strychnine
When studying ionotropic post synaptic glutamate receptors, if the postsynaptic membrane has a higher potential (-40mV) will Ca2+ flow into the postsynaptic membrane?
yes, due to the activation of NMDA as well as AMPA.
Which ligand channel comes from a different evolutionary line than the other ligand gated channels?
glutamate
Where is ACh synthesized?
cytoplasm
How long ago did the oligopentamer ligand gated channels first appear?
800 million years ago
What terminates the action of ACh in the synaptic cleft?
AChE - acetylcholinesterase
EPPs (such as ACh release and binding to a postsynaptic membrane) have a smaller delay when they are at what location?
closer to the motor endplate or the presynaptic terminal.
How many binding regions are located on a GABAa receptor?
3 (a1, B1,y2)
How many TM regions does the most ancient ligand channel have?
4 subunits x 3TM per unit = 12 TMs total (glutamate)
What are the 2 cation ligand receptors?
GABAaR and GlyR
By strictly adding benzodiazepine to a GABAa channel, without the presence of GABA, what will happen to the Cl- current?
The Cl- current will be unchanged without the presence of GABA.
What drug will cause an increase in the frequency of GABAa channel opening?
benzodiazepines (valium)
How many NMDA-type subunits are there in a glutamate ionotropic receptor?
5 (1, 2A, 2B, 2C, 2D )
by activated Glycine or GABAa channel , what type of ion current will increase?
Cl- they are inhibitory because they restore membrane potential.
When studying ionotropic post synaptic glutamate receptors , an EPSP is the sum of what 2 currents?
1.the rapid component AMPA current 2.the slow component NMDA current
What is defined as “an potential that is equal to the sum of multiple EPSP or IPSPs that are received at a postsynaptic NEURON at consecutive time intervals in order to reach threshold and exhibit an action potential (or inhibit an AP in the case of IPSP)”
temporal summation
List the ionotropic receptors that consist of 4 subunits (tetramers):
- glutamate
IPSPs are mediated by what type of channels? anion or cation?
anion channels
During a I-V plot, you find that the reversal potential is 0 mV. What type of current or channel is present?
a nonselective cation channel in a NMJ. (nicotinic ACh receptor)
What would you predict the reversal potential (or nernst potential) of a current that does not differentiate between Na and K ions?
0 mV. such channels are called nonselective cation channels.
Strychnine blocks ligand gated channels located where in the body?
CNS –> spinal cord and brainstem.
If in an experiment the IPSP is not present at a certain voltage (-70mV) , that voltage is equal to…
the reversal potential of that channel. identifying it as a Cl channel due to its Ecl. (Cl-)
Glycine and GABAa ligand gated channels both function to open what kind of ion channel?
Cl- channels (causing inhibition)
How many TM regions exist in a complete Nicotinic Ach receptor ?
5subunits x 4TM per unit = 20TM
In Gprotein coupled reception: What happens after the inward rectifier K+ channels are activated?
Depolarization of the cell occurs due to an influx of K+
By strictly adding barbiturates to a GABAa channel, without the presence of GABA, what will happen to the Cl- current?
The Cl- current will be unchanged without the presence of GABA.
Where are GlyR found?
CNS —> spinal cord, brainstem
When studying ionotropic post synaptic glutamate receptors, which receptor is independent of postsynaptic membrane potential?
AMPA
What type of ligand channel is considered to be the most ancient?
Glutamate
Which of the 2 main types of glutamate ionotropic glutamate receptor has slower kinetics?
NMDA
When studying ionotropic post synaptic glutamate receptors, if the postsynaptic membrane has a very low membrane potential will there be a fast or slow depolarization?
fast depolarization due to AMPA activation and little activation of NMDA.
which ligand receptor is responsible for inhibition in the PNS?
Glycine
If in an experiment the EPSP is not present at a certain voltage(0mV), that voltage is equal to …
the reversal potential of that ligand gated cation channel.(Ecation) equally permeable to K and Na
What type of ligand receptor contains binding regions on its a1, B1, and y2 subunits?
GABAa
each subunit in a voltage-gated ion channel consists of how many helical segments?
6
What is the order of the subunits of an AChR starting with its first a-subunit moving counterclockwise?
a,B,a,y,g OR a,y,a,B,g (B and y can be switched, this is in counterclockwise rotation)
Where are the receptor sites located within a Nicotinic Ach receptor?
the alpha subunits
Which type of ligand receptor has only 3TM regoins per subunit?
glutamate
EPPs (such as ACh release and binding to a postsynaptic membrane) are weakest at what location?
a further distance from the motor endplate or the presynaptic terminal.
How many subunits are located on the most ancient ligand channel?
4subunits (glutamate)
In Gprotein coupled reception: what follows the release of the subunits of the G-protein?
activation of inward rectifier K+ channel by the By (beta-gamma) subunit
EPPs (such as ACh release and binding to a postsynaptic membrane) have a greater delay when they are at what location?
a further distance from the motor endplate or the presynaptic terminal.
What are the 2 main types of ionotropic glutamate receptors?
- AMPA 2. NMDA
List the ligand gated channels that consist of 5 subunits (pentamers):
- ACh 2. GABAa 3. glycine 4. serotonin (5-HT)
When studying ionotropic post synaptic glutamate receptors, which channel is blocked by Mg2+ until it is displaced by a higher potential in the post synaptic membrane?
NMDA
What drug will cause an increase in the duration of a GABAa channel opening?
barbiturates
If a reversal potential in a postsynaptic membrane of a NMJ were to be equal to 0, what could you conclude?
The nicotinic ACh receptor has a poor selectivity for Na+ and K+
In Gprotein coupled reception: what follows the activation a Muscarinic ACh receptor?
release of a-GTP and By (beta-gamma) from the heterotrimeric G protein.
What 2 ligand gated channels are associated with inhibition or IPSPs?
Glycine and GABAa
A mGluR1 has how many membrane spanning regions?
7 - because it is coupled with a gprotein and is metabotropic.
What 2 ligand gated channels are associated in openning Cl- channels?
Glycine and GABAa
What are the NMDA-type subunits in a glutamate ionotropic receptor?
NMDAR1, NMDAR2A, NMDAR2B, NMDAR2C, NMDAR2D )
At neuronal synapses (unlike NMJ) synaptic potentials are usually either _______ or ______
excitatory or inhibitory
Which of the 2 main types of glutamate ionotropic glutamate receptor is permeable to Ca2+ (always) ?
NMDA
The activation of action potentials in the CNS usually depends on _____ or _____ of multiple subthreshold EPSPs and IPSPs.
integration or summation
What are the 2 types of neurotransmitter receptor molecules ?
Ionotropic(ie ligand gated channels) Metabotropic (ie. Gprotein coupled receptors)
Where did the oligotetramer ligand gated channel come from?
descendent of early K+ channels /transporters
When studying ionotropic post synaptic glutamate receptors, if the postsynaptic membrane has a very low membrane potential which channel will not open?
NMDA because the potential isn’t high enough to displace Mg2+
nonselective cation channels can be permeable to what 2 types of cations?
monovalent (+1) or divalent (+2)
each subunit of an AChR consists of how many TM regions?
4
When studying ionotropic post synaptic glutamate receptors, if the postsynaptic potential is very negative (around -80mV) what happens to the measured currents through each channel?
If post synaptic potential is low (around -80mV) 1. the NT (glutamate) binds to the AMPA receptor and depolarize the cell. 2. there is little to no contribution of current from the NMDA receptor because the potential is too low to displace Mg2+ blocking it.
how many subunits are within a Nicotinic Ach receptor?
5 subunits . (2a, B, y, g) heteroligmer Pentamer
When studying ionotropic post synaptic glutamate receptors, if the postsynaptic membrane has a lower potential (-80mV) will Ca2+ flow into the postsynaptic membrane?
no, because the postsynaptic potential is too low to active NMDA glutamate receptors. Only AMPA will be activated.
What type of ligand receptor contains binding region on its a and B only?
glycine
Why are EPPs weaker at a greater distance from the motor endplate?
ACh (or any NT) is terminated by a present enzyme that quickly destroys the NT before it can reach the terminal.
What is the result of ACh binding to the postsynaptic membrane ?
it causes an excitatory postsynaptic potential that decays with distance from its site of action. (last chapter)
When studying ionotropic post synaptic glutamate receptors which receptor is dependent on the postsynaptic membrane potential?
NMDA
In Gprotein coupled reception: what would happen following the Depolarization of a cardiac Muscle cell ?
it would lead to a decrease in heart rate.
Which ligand receptor is responsible for inhibition in the CNS?
GABAa
which receptor channel is the most important inhibitory receptors in the brain?
GABAa mediate the effects of barbiturates and benzodiazepenes (valium)
In Gprotein coupled reception: What NT activates a Muscarinic ACh receptor?
ACh (duh)
How many binding regions are located on a Nicotinic Ach receptor?
2
Which of the 2 main types of glutamate ionotropic glutamate receptor has faster kinetics?
AMPA
In either temporal or spatial summation, What can be seen in the nodes of Ranvier throughout the axon of the neuron?
Only “spikes” or action potentials of Summed EPSPs that reached threshold.
What are the 2 anion ligand receptors?
5-HT3R(seratonin) and nAChR
Between Glycine and GABAa, which type of channel has a greater single channel current?
Glycine
What is a AChR called?
Nicotinic Ach receptor
AMPA is the glutamate receptor that mediates the great majority of fast excitatory transmission in which Nervous system?
CNS
