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My name is Vladimir Parpura.
I will talk about various mechanisms
of glutamate release from astrocytes,
a subtype of glial cell
in the nervous system.
Neuroglia was first time
described in 1856 by the German
neuropathologist Rudolf Virchow
as a putty that binds nervous
elements together, somewhat like
cement that binds the bricks.
The Spanish neuroanatomist Santiago
Ramon Y Cajal proposed that neuroglia,
shown in dark brown in his drawing,
have a more active role in the brain,
since their position at
the interface between blood vessels,
shown in A, and neurons, shown in C and D.
We know today that the gold
sublimate stain that he used
targeted intermediate filaments
that consist mainly of
glial fibrillary acidic
protein abbreviated as GFAP,
which is used today as
an astrocytic marker.
This slide shows an image of purified
cultures of astrocytes stained
using indirect immunocytochemistry with
an antibody against GFAP, shown in red.
The cell nuclei shown in
blue are stained using DAPI.
Such cells in culture were
instrumental in describing various
mechanisms utilized by astrocytes for
the release of the major
excitatory transmitter glutamate
as summarized in the next slide.
There are six known mechanisms of
glutamate release from astrocytes,
shown clockwise in the order
of their discoveries,
along with original references.
1, swelling induced opening of
volume regulated anion channels.
2, reverse operation of excitatory
amino acid transporters.
3, calcium dependent exocytosis.
4, the cysteine glutamate exchanger.
5, connexin hemichannels.
And 6, the purinergic P2X7 receptors.
I'll discuss each of these mechanisms,
although not in order
of their discoveries.
I will start the discussion of glutamate
release through plasma membrane
transporters, such as the reversal
of uptake by excitatory amino acid
transporters, and exchange by
the cysteine glutamate antiporter.
Then I will follow up by
a more detailed discussion
of glutamate release through
calcium dependent exocytosis.
And finally I will discuss glutamate
release through channels on the cell
surface, such as anion channel
opening induced by cell swelling,
released ionotropic purinergic receptors,
and by unpaired connexin.