Lecture 2: Synaptic Transmission and Plasticity Cont'd Flashcards Preview

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Flashcards in Lecture 2: Synaptic Transmission and Plasticity Cont'd Deck (63):
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2 classes of glutamate transporters: 1. 2.

1. iGluRs 2. mGluRs

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iGluRs

Glutamate-gated ion channels, glutamate-binding leads to channel opening

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mGluRs

A group of GPCRs. Glutamate binding activates G-protein signaling.

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3 subtypes of iGluRs 1. 2. 3.

1. AMPA-R (non-NMDA) 2.KA-R (non-NMDA) 3. NMDA-R

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KA-R stands for...

Kainic acid receptor

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Where is KA-R expressed?

Only in some synapses. Not very common in the brain.

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Subunits of AMPA-R

GluA1-4

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Subunits of KA-R

GluK1-3, GluK4-5

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Subunits of NMDA-R

GluN1, GluN2A, B, C, D, GluN3A, B

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GluA1-4 were previously known as _______.

GluR1-4

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GluK1-3 were previously known as _______.

GluR5, 6, 7

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GluK4-5 were previously known as _______.

KA1, 2

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GluN1 was previously known as _______.

NR1

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GluN2A, B, C, D were previously known as _______.

NR2A-D

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GluN3A, B were previously known as _______.

NR3A, B

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How many groups of mGluRs are there?

3

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Subunits of group 1 mGluRs: _______.

mGluR1, 5

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Subunits of group 2 mGluRs: _______.

mGluR2, 3

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Subunits of group 3 mGluRs: _______.

mGluR4, 6, 7, 8

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Most NMDA-Rs contain at least 1 _______/_______ subunit.

GluN1/NR1

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Activation of iGluRs leads to _______ entry, causing a rapid depolarization of postsynaptic membranes, known as _______.

Cation; EPSP

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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)

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The subunit of the iGluR determines its _______ and _______ properties.

Electrophysiological; pharmacological

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Which subunit forms the pore of the iGluR?

M2 (4 of them interact to form the pore)

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What subunit composition makes an NMDA-R permeable to calcium?

The ones that LACK GluR2.

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Why are NMDA-Rs always permeable to calcium?

Because they never contain GluR2.

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Can AMPA-Rs be permeable to calcium?

Yes, so long as they don't contain GluR2.

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iGluRs are permeable to ___ and ___, while some are permeable to ___.

Na+ (in), K+ (out), sometimes Ca++

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How many glutamate molecules must bind to an iGluR to cause it to open?

2

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Activation of iGluRs causes _______.

EPSP

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3 agonists for AMPA-3 1. 2. 3.

1. AMPA

2. Demonic acid

3. Quisqualic acid

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2 agonists fo NMDA-R 1. 2.

1. NMDA 2. Aspartate

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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

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AP-5

NMDAR antagonist. Competitive inhibition.

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MK-801

NMDAR antagonist. Open channel blocker.

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Ketamine

NMDAR antagonist. Anesthetic.

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Ifenprodil

NMDAR antagonist. Selective for NR2B.

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Ro25-6981

NMDAR antagonist. Selective for NR2B.

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NVP

NMDAR antagonist. Selective for NR2A.

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Antagonists of AMPAR: 1. 2. 3. 4.

1. CNQX 2. GYKI-52466 3. Kynurenic acid 4. NBQX

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CNQX

Antagonist of AMPAR + KA-R.

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GYKI-52466

Antagonist of AMPAR. Highly selective for AMPAR.

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Kynurenic acid

Antagonist of AMPAR. Endogenous and non-selective.

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NBQX

More selective for AMPAR.

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AMPA-R mediates a ______ component of the EPSP.

Fast

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NMDA-R mediates a ______ component of the EPSP.

Slow

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Which iGluR causes a low amplitude, long duration EPSP?

NMDA-R

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Which iGluR causes a high amplitude, short duration EPSP?

AMPA-R

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Which has a higher conductance: NMDA-R or AMPA-R?

AMPA-R

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Which receptor does the orange component represent? What about the brown component?

Q image thumb

Orange: AMPA-R

Brown: NMDA-R

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Why is the AMPA-R short duration?

Because it is easily  desentitized.

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Why is the NMDA-R long duration?

Because it has a higher affinity for glutamate.

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When the membrane potential is at -70 mV, ____ clogs the pore of the _____, preventing cation conductance, even when glutamate is bound.

Mg++; NMDA-R

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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.

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AMPA-R mediates the ______ and ______ amplitude of EPSPs.

Fast; large

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AMPA-R quickly ______ in respond to its ligand (agonist).

Desensitizes

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Most of AMPA-Rs are impermeable to calcium, but AMPA-Rs lacking ______ are permeable to calcium.

GluR2

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The NMDA-R is a ______, but the conductance is ______, not ______.

Ligand-gated ion channel; voltage-dependent; NOT voltage-gated.

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The gating of the NMDA-R is mediated by ______.

The dependence of the NMDA-R is mediated by ______.

Glutamate; voltage

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***KNOW THIS: What are the 4 unique features of the NMDA-R?

1.
2.
3.
4.

 

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.

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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.

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The NMDA-R requires coactivation by ______, and ______.

Glutamate; glycine/D-serine

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