2 classes of glutamate transporters: 1. 2.
1. iGluRs 2. mGluRs
Glutamate-gated ion channels, glutamate-binding leads to channel opening
A group of GPCRs. Glutamate binding activates G-protein signaling.
3 subtypes of iGluRs 1. 2. 3.
1. AMPA-R (non-NMDA) 2.KA-R (non-NMDA) 3. NMDA-R
KA-R stands for...
Kainic acid receptor
Where is KA-R expressed?
Only in some synapses. Not very common in the brain.
Subunits of AMPA-R
Subunits of KA-R
Subunits of NMDA-R
GluN1, GluN2A, B, C, D, GluN3A, B
GluA1-4 were previously known as _______.
GluK1-3 were previously known as _______.
GluR5, 6, 7
GluK4-5 were previously known as _______.
GluN1 was previously known as _______.
GluN2A, B, C, D were previously known as _______.
GluN3A, B were previously known as _______.
How many groups of mGluRs are there?
Subunits of group 1 mGluRs: _______.
Subunits of group 2 mGluRs: _______.
Subunits of group 3 mGluRs: _______.
mGluR4, 6, 7, 8
Most NMDA-Rs contain at least 1 _______/_______ subunit.
Activation of iGluRs leads to _______ entry, causing a rapid depolarization of postsynaptic membranes, known as _______.
How many subunits can be found in each iGluR? How many transmembrane domains are found in each subunit?
4 (tetrameric); 4 TM domains (16 in total)
The subunit of the iGluR determines its _______ and _______ properties.
Which subunit forms the pore of the iGluR?
M2 (4 of them interact to form the pore)
What subunit composition makes an NMDA-R permeable to calcium?
The ones that LACK GluR2.
Why are NMDA-Rs always permeable to calcium?
Because they never contain GluR2.
Can AMPA-Rs be permeable to calcium?
Yes, so long as they don't contain GluR2.
iGluRs are permeable to ___ and ___, while some are permeable to ___.
Na+ (in), K+ (out), sometimes Ca++
How many glutamate molecules must bind to an iGluR to cause it to open?
Activation of iGluRs causes _______.
3 agonists for AMPA-3 1. 2. 3.
2. Demonic acid
3. Quisqualic acid
2 agonists fo NMDA-R 1. 2.
1. NMDA 2. Aspartate
Antagonists for NMDA-R 1. 2. 3. 4. 5. 6.
1. AP-5 2. MK-801 3. Ketamine 4. Ifenprodil 5. Ro25-6981 6. NVP
NMDAR antagonist. Competitive inhibition.
NMDAR antagonist. Open channel blocker.
NMDAR antagonist. Anesthetic.
NMDAR antagonist. Selective for NR2B.
NMDAR antagonist. Selective for NR2B.
NMDAR antagonist. Selective for NR2A.
Antagonists of AMPAR: 1. 2. 3. 4.
1. CNQX 2. GYKI-52466 3. Kynurenic acid 4. NBQX
Antagonist of AMPAR + KA-R.
Antagonist of AMPAR. Highly selective for AMPAR.
Antagonist of AMPAR. Endogenous and non-selective.
More selective for AMPAR.
AMPA-R mediates a ______ component of the EPSP.
NMDA-R mediates a ______ component of the EPSP.
Which iGluR causes a low amplitude, long duration EPSP?
Which iGluR causes a high amplitude, short duration EPSP?
Which has a higher conductance: NMDA-R or AMPA-R?
Which receptor does the orange component represent? What about the brown component?
Why is the AMPA-R short duration?
Because it is easily desentitized.
Why is the NMDA-R long duration?
Because it has a higher affinity for glutamate.
When the membrane potential is at -70 mV, ____ clogs the pore of the _____, preventing cation conductance, even when glutamate is bound.
When does Mg++ clog the pore of the NMDA-R?
When the membrane potential is at -70 mV. By the time it depolarizes to -40 mV magnesium no longer attracts the membrane as much, allowing Na+ and Ca++ to pass through.
AMPA-R mediates the ______ and ______ amplitude of EPSPs.
AMPA-R quickly ______ in respond to its ligand (agonist).
Most of AMPA-Rs are impermeable to calcium, but AMPA-Rs lacking ______ are permeable to calcium.
The NMDA-R is a ______, but the conductance is ______, not ______.
Ligand-gated ion channel; voltage-dependent; NOT voltage-gated.
The gating of the NMDA-R is mediated by ______.
The dependence of the NMDA-R is mediated by ______.
***KNOW THIS: What are the 4 unique features of the NMDA-R?
1. It requires co-activation by two ligands: glutamate and glycine/D-serine
2. Its activation is both ligand-gated and voltage-dependent (channel pore is blocked by Mg2+ at VR) - But it is NOT a voltage-gated channel!!!
3. It is highly permeable to Ca2+ . Ca2+ flux through NMDA-Rs is thought to play a critical role in synaptic plasticity, a cellular mechanism of learning and memory.
4. It is subject to modulations by various drugs.
What is the most important feature of the NMDA-R?
It is highly permeable to calcium, which forms the basis for learning and memory via synaptic plasticity.
The NMDA-R requires coactivation by ______, and ______.