PSYC 455 Lecture Notes - Lecture 10: Glutamate Transporter, Glutaminase, Glutamatergic
26 Apr 2018
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PSYC 455
Lecture 10 – Excitatory Amino Acids
• Excitatory Amino Acids
1. Neurotransmitter that acts on an excitatory amino acid receptor:
a. Include:
- Aspartate (Asp)
- Cystate.
- Homocystate
- Glutamate (Glu):
i. Most abundant neurotransmitter (i.e. primary excitatory input) in the
brain along with its inhibitory cousin, GABA.
• Glutamate
1. Synthesis and Termination:
a. Production:
- Produced de novo/from scratch:
i. Synthesized from glucose (from the CREB cycle) or from glutamine
(a.k.a. glutaminase)
b. Transportation:
- Once it is synthesized at the terminal, Glu is transported to the vesicles via
VGluT (Vesicular Glutamate Transporters):
i. How this works:
We have a large concentration of Protons (H+) inside the vesicle:
Caused by another transporter on the Glu vesicle (i.e. the
Proton antiporter):
1) Uses ATP to transport protons into the vesicles (i.e.
creating a concentration gradient)
Glu is brought into the vesicle via the concentration gradient (i.e.
for every 1 proton/H+ that leaves the vesicle, it powers VGluT to
take in 1 Glu neurotransmitter into the vesicle):
Basically:
1) As the protons want to flow out of the vesicle, they
activate the VGluT, bringing Glu into the vesicle.
c. Release:
- The vesicles fuse with the pre-synaptic membrane of the Glutamatergic
neuron and release Glu into the synapse:
i. What happens when there is too much Glu in the synapse:
Causes excitotoxicity (i.e. an excessive release of Glu and an over
excitation of the surrounding neurons; causing neuron death due
to over excitation):
Mother Nature’s safet ets for this system:
1) The BBB
2) The glia cells (Astrocytes) found wrapped around the
synapse who have their own EAATs:
a) Steps:
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PSYC 455
Lecture 10 – Excitatory Amino Acids
The excessive Glu will be taken up by these
astrocytes (kind of like a buffer).
The astrocytes will convert the glutamate into
glutamine (i.e. a storage system of excessive
glutamate).
Glutamine will then get carried back to the neuron
by a System A transporter
d. Termination:
- Excitatory Amino Acid Transporter (EAAT) reuptakes Glu back into the cell:
i. EAAT is powered by a sodium concentration gradient
• EAA Receptors
1. G-Protein Coupled (Metabotropic) Receptor:
a. mGluR (metabotropic Glutamate Receptor):
- Three groups:
i. Group 1 (Gq receptors):
mGluR1 and mGluR5
ii. Group 2 (Gi or Go; inhibit or have no effect on adenylyl cyclase):
mGluR2 and mGluR3
iii. Group 3 (Gi or Go; inhibit or have no effect on adenylyl cyclase):
mGluR4 to mGluR8
b. AP4:
- Possibly an mGluR subtype (i.e. mGluR8)
2. Ligand-Gated Ion Channels:
a. NMDA (N-Methyl-D-Aspartate) Receptors:
- High density in the hippocampus and cortex:
i. Receptor is critical for learning
- Pentameter with 5 subunits made up of a combination of NR1, NR2, NR3
subunits (these subunits have many subtypes of their own, so many
combinations are possible):
i. Binding sites:
Magnesium:
Inside the channel:
1) When the Mg channel is open, NMDA is permeable to:
a) K+
b) Ca2+
c) Na+
Voltage gated:
1) Recall:
a) The inside of a neuron at rest is -65mV.
2) Mg+ has a + charge:
a) So, when the neuron is at rest (i.e. more negative), it
causes Mg+ to go and get stuck in its receptor causing
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Document Summary
Lecture 10 excitatory amino acids: excitatory amino acids, neurotransmitter that acts on an excitatory amino acid receptor, include: Most abundant neurotransmitter (i. e. primary excitatory input) in the brain along with its inhibitory cousin, gaba: glutamate, synthesis and termination, production: Synthesized from glucose (from the creb cycle) or from glutamine (a. k. a. glutaminase: transportation: Once it is synthesized at the terminal, glu is transported to the vesicles via. We have a large concentration of protons (h+) inside the vesicle: Caused by another transporter on the glu vesicle (i. e. the. Proton antiporter): uses atp to transport protons into the vesicles (i. e. creating a concentration gradient) Glu is brought into the vesicle via the concentration gradient (i. e. for every 1 proton/h+ that leaves the vesicle, it powers vglut to take in 1 glu neurotransmitter into the vesicle): Basically: as the protons want to flow out of the vesicle, they activate the vglut, bringing glu into the vesicle, release:
