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6.2 The Na+ gating current
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来自 Peking University 的课程
Advanced Neurobiology I
236 个评分
从本节课中
Ion channels, membrane potential and synaptic transmission
Let's continue with the ion channels, membrane potential and synaptic transmission.
与讲师见面
Yan ZhangProfessor
School of Life Sciences, Peking University
Yulong LiResearch Fellow
School of Life Sciences, Peking University
Where you have a large abundance of sodium, potassium channels.
For example, if you want to measure the sodium gating currents, how do you do it?
First, you block all other ion channels because you only
want to measure the current mediated by the gating particle movements.
And so, you block potassium channels, blah, blah, blah, meaning other channels.
And then, actually, you also block the [INAUDIBLE] channels.
Because, your prediction will be, well, if you block this port,
If you are still in the right electrical field,
these skating particles in the electrical field, they are still going to move.
But because they block the sodium channels, then this will be good.
You have less background currents, so you are able to,
more precisely, measure the gating currents.
So, here is the result.
[COUGH] So, you can measure the gating of sodium
in the presence of TTX and blocking all the rest of other ion channels and
you'll see there's this Current changes.
Okay, this is a gating current.
And if you are not using the TTX, what you observe is
that you have this gating trapped current, but then,
the immediate opening of the sodium channel will
allow the sodium influx, so then you have this compound.
You have both of the gating current and
this water gated through the channel opened, mediated the current influx.
And this arrangement, actually, is not bad, because the direction of
the gating current is different than the direction of the sodium currents.
But the not blocking the sodium current.
And if we are starting the potassium channel changing current.
If we are in the same direction, then there is almost no way for
you to separate the current mediator by opening of those iron channel or
the current due to the movement of this charged particles.
And, so, these measurements, you actually can do mutagenesis from them.
More precisely, you can mutate those grating particles
that you can postulate the or and then,
you're prediction would be well, then that would be less current if they move.
And your prediction will also be that because of the, so
this is one of the example of the Shaker potassium channel.
You can block the potassium channel and you can measure the gating current.
And you can find that during the depolarization,
the gating current is from one direction.
And I'll tell you, going back to the resting condition,
the gating particle also move back.
So, the iron channel that has this confirmation that you will
move at certain wattage, and
then move back once you moving the wattage back to the original state.
But if you look here, as you can see that the moving speed might be different.
So, for example, moving towards this end tends to be faster
than moving back to the resting state.
And then if you are really the opening of the ion channel
which is shown g is in conductance under a different voltages.
You found that the wattage channels will open at different wattages so
you can measure to this conductance.
So this indicates that there is a sodium current or
potassium current going through this ion channel in the wattage dependent manner.
But if you superimpose the gating current measurement,
what he found is he also has the water dependency, but
it moved faster or the curve is left shifted.
What does that mean?
This indicates that the gated particle already moved
even before to the opening of the ion channel.
For example, this ion channel open can be described by this G.
About -50 millivolt this ion channel are start to open.
So you can see this is a certain current.
But what you found actually, the ion channel itself
are already start to undergo conformational changes.
Starting probably from minus 75 million volts,
it already starts to change its confirmation.
We sort of change a lot of confirmation.
Here, you have a large gating current.
Okay, gating current measurement indicates how
much the confirmation of change happening.
How much is the charged particle are moving in the electrical field?
If they move the largest distance, you will create the largest current.
So, in this case, you can understand well,
after this gating particle in this S4 region that are moving a lot.
You already created for example about 50% of the grating particle
movements you start to have the opening of this ion channel.
So this plot indicates that it is this voltage sensor that first moves.
They first move and then subsequently dragging the pore to open.
Because the voltage dependency is left shifted.
Any questions so far?
[COUGH] And this is the experiment that, again,
some of our students suggest that indeed, for
example, MacKeenen, mutate those sides,
and then they measured The [INAUDIBLE]
dependency art during the recording.
For example, certain reside is more important than
the because when you are moving it, mutating it,
you are actually significantly, shift locating particles changes.
And then the currently this people are still debated
that what is actually the gating particle looks like.
Previously before the crystal structure,
people postulate that it is gating particle might originate in
a confirmation that some of them have moved in this vertical directions.
But with more crystal structure studies,
many the studies from Rotmokines lab that when they
crystallize with the help of some antibodies,
they found that actually locating particles is
not in the but rather it's like a paddle.
And then you will sort of vertically move the paddle wheel so
the tilt slight to mediate the confirmation.
