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0:00
Hello.
I'm Stephanie Schorge, and I am
at the Royal Society University
Research Fellow working
here in the Department
of clinical and
experimental epilepsy
at the UCL Institute of Neurology.
And I'm going to talk today
about some functional insights
we have from human
genetic channelopathies
and how we think they
are linked to disease.
0:21
So the aim of this lecture, to
begin with, is to first of all,
give you an overview
of what channelopathies
are without giving an entire list.
And then I'm going to give an
overview of how genes are made
into ion channels
in five easy steps.
And for each of
those steps I'm going
to illustrate with
a specific example
of a particular channelopathy
that I've carefully
cherry picked to
focus in on one step.
And there are many, many other
channelopathies that I won't
mention, but the ones
that I do mention
are going to be those that
I have tried to isolate
specifically to
highlight those steps.
0:52
So we're in the genomic era.
And that makes life
much, much easier
for people who link ion
channels to diseases.
And this means that at this point,
finding a mutation in an ion
channel is less about finding
the gene and more just about
sequencing ion channels.
And the reason that most ion
channel-related diseases have
a neurological component is not
because neurons have all the ion
channels, but just that neurons
have most of the ion channels.
All cells, all living
cells have ion channels,
and you can almost
define a living cell
by the presence of ion channels.
And neurons in particular not just
because they have ion channels,
but because just about every ion
channel you have is in some neuron
somewhere.
So if you have a mutation
in an ion channel genes,
there's a very high
probability it's going
to affect some neuron somewhere.
So in the original incarnation,
because people who study ion
channels frequently have
been biophysicists who
look at the functioning
of intact channels,
our first conception was to find
these mutations in ion channel
genes and to express those and
to look at the channelopathy
as a change in the function
of an intact channel
with one amino acid changed, or
one or two inserted or deleted.
However, since we've entered this
era of vast amounts of sequencing,
we realize that many
channelopathies, if not most
channelopathies, they don't
just disrupt a single nucleotide
and a single amino acid, but they
will change the product of the gene
before the mRNA, the protein, ever
gets made and into the membrane
where the channel
would normally work.
And as I'll try to link to
throughout this lecture,
the treatments that we have
for diseases associated
with channelopathies are just
beginning to recognize that we may
not be treating a
channel in the membrane.
We may be treating an RNA
before it becomes a channel.
