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Today's presentation is on the
structure of the GABAA receptor.
For the central nervous
system to function
it has to have a
degree of excitation,
but that excitation
can't be unstructured.
And one of the most important
ways to control this
is by neurotransmitter GABA
activating GABAA receptors to cause
inhibition in the nervous system.
Before we look at the
structure of the receptor,
I'd just like to take you through
some elementary, basic introductory
features of GABAA
receptors and GABA itself.
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When you look at the
central nervous system,
GABA and GABAA receptors are
spread quite ubiquitously right
across the entire area of
the brain and spinal cord.
This is because they are
involved in two very important
physiological control
mechanisms that are called
synaptic inhibition
and tonic inhibition.
Synaptic inhibition involves
the pulsatile release
of relatively high concentrations
of GABA at inhibitory synapses,
whereas tonic inhibition is
really the assistant level
of low concentrations of GABA
activating GABA receptors which lie
outside the synapse, the so
called extra-synaptic domain.
Both of these aspects are important
for controlling the spiking, action
potential firing of
individual nerve cells.
There's another factor that's
important for GABAA receptors
and that's in development, during
early on in immature neurons where
by GABA can cause the
outgrowth of neurites
and the development of neurons.
So there are many important
physiological features
that are associated with
GABAA receptors and GABA.
Now when there's dysfunction,
this can involve a number
of different diseases
in the GABA system.
Some diseases can be directly
attributed to GABAA receptor
dysfunction, such as
anxiety and epilepsy.
And other diseases and
conditions are less direct,
and this could be depression,
Down's Syndrome, schizophrenia
for example, Alzheimer's
disease, and pain.
But nevertheless,
this slide shows you
that not just physiologically,
but pathologically, GABA has
important roles to play
in the nervous system.
Now because of this,
GABA receptors have
become natural targets for drugs.
Some are listed here
on the right hand side.
Barbiturates, Benzodiazepines,
general anesthetics, and there
are endogenous regulators of GABA
receptors called neurosteroids.
And it's no surprise then to
find that a number of drugs
are through to the
market and are involved
in the treatment of a
variety of diseases.
You'll notice that these
are dominated by epilepsy.
But there's also conditions whereby
GABAergic drugs could be used
for the treatment of
pain, and also more
recently for Alzheimer's disease.
So what does the natural
GABA receptor look like?
This we can see in the next slide.
