6.5 Ion channel, membrane potential and synaptic transmission II

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Del curso dictado por Peking University

Advanced Neurobiology I

258 calificaciones

Peking University

Advanced Neurobiology I

258 calificaciones

Hello everyone! Welcome to advanced neurobiology! Neuroscience is a wonderful branch of science on how our brain perceives the external world, how our brain thinks, how our brain responds to the outside of the world, and how during disease or aging the neuronal connections deteriorate. We’re trying to understand the molecular, cellular nature and the circuitry arrangement of how nervous system works. Through this course, you'll have a comprehensive understanding of basic neuroanatomy, electral signal transduction, movement and several diseases in the nervous system. This advanced neurobiology course is composed of 2 parts (Advanced neurobiology I and Advanced neurobiology II, and the latter will be online later). They are related to each other on the content but separate on scoring and certification, so you can choose either or both. It’s recommended that you take them sequentially and it’s great if you’ve already acquired a basic understanding of biology. Thank you for joining us!

De la lección

Ion channels, membrane potential and synaptic transmission

Let's continue with the ion channels, membrane potential and synaptic transmission.

6.1 Voltage sensing15:39

6.2 The Na+ gating current8:04

6.3 Inactivation gates17:37

6.4 Ion channel, membrane potential and synaptic transmission I15:12

6.5 Ion channel, membrane potential and synaptic transmission II7:30

6.6 Ion channel, membrane potential and synaptic transmission III12:53

6.7 Ion channel, membrane potential and synaptic transmission IV7:01

6.8 Ion channel, membrane potential and synaptic transmission V9:44

Conoce a los instructores

Yan Zhang
Professor
School of Life Sciences, Peking University
Yulong Li
Research Fellow
School of Life Sciences, Peking University

If we want to understand

calcium's essential role of transmitter release, okay?

We have to first establish a model

system that we can study transmitter release, right?

We've got to be able to detect transmitter release from certain preparation.

Okay, and then we sort of perturb calcium, and

then to see whether the transmitter release is order or not, right?

Okay so, how do we do it?

We have little reagents, but most importantly in the old days, and still

now, we have one of the simple preparation which is the neuromuscular junction.

Okay, well the nerve cells will release transmitter to the muscle.

And this is a pretty good model system.

The reason is that well, it's relatively easy to isolate

this nerve with the muscle from frog, from mice.

Okay, and one especially advantage is that the muscle cell are pretty big, okay.

So, if we want to record from the muscle cell, their electrical response,

their post-synaptic response, it's relatively easy.

Okay with the smooth cells.

Nowadays, it's much easier with the modern technique, but in the old days,

much more difficult, okay?

So, for example you already have the neuromuscular

junction preparation and then you can.

You can stimulate using the electrode to trigger the action potential,

the nerve, okay?

And then you have another electrode in the post-synaptic cell, in the muscle.

Once you stimulate and it says, in the regular condition with the regular

solution that it has normal calcium in the solution for example, 2 million molar.

What you observe is you can record the transmitted release

by recording the post-synaptic response to the transmitted release.

Well, there is some depolarization and

if you can imagine the current that mediates it.

The depolarization that EPS sees.

Okay then how do you

design your experiment to demonstrate calcium is important?

Okay, you can remove calcium.

How do you remove calcium?

>> [INAUDIBLE] >> To engineer buffers so well.

You note we are making the buffers.

You note its composition, right.

So we are making new buffer.

You are eliminating calcium.

So you can make new buffer without calcium.

And sometimes you can add different divalent ions with them

if you know calcium is important, well,

if you remove calcium you are not only removing this calcium,

because you are also changing the ionic composition,

where you can just replace, you're adding the similar amount of mechanism.

Okay, it's the same concentration, and you do that experiment.

Okay, so you can record the nervous bounce, and

then you can profuse the cell, without external calcium, and

then low and behold you found, there's no transmitter with this, okay?

And indeed, people do that experiment,

they found there's not transmitter release.

And you can even do more sophisticated experiments that,

rather than directly removing calcium, you could use the calcium chelator.

For example, this is one of them, called EGTA.

Now EGTA is a chelator alkalinity that it can selectively chelate calcium, okay.

And so you can add enough chelator to chelate the calcium and

then you can look at the synapse transmission response again.

The synapse transmission might be gone.

So why do you want to add the EGTA?

Could you add the EDTA?

EGTA is another chelator.

And it can also chelate calcium.

But people for

the physiological study of calcium response usually will not use EGTA.

Well, indeed EGTA can chelate calcium, but it is not so specific.

You can also chelate magnesium, you can also chelate zinc,

okay, you can chelate iron, you can chelate a lot of ions.

All right, so that's the reason your EGTA might not be so specific.

In fact,

in the EDTA has already been widely used to stop some chemical reactions.

For example if we are digesting some DNA with some restriction enzymes, okay.

And then a lot of times you can add EDTA to heating mechanism.

Okay because those restriction enzymes rely on the mechanism

as a co-factor to be catalytic active okay?

So EDTA has been useful for that.

But if you want to specific EGTA is one of it.

But the EGTA is a slow buffer,

meaning that it can chelate calcium, but it binds to calcium relatively slow.

And therefore, people,

like Roger Tsien invented data, EGTA homolog,

it's called BAPTA, that is similar as EGTA,

but it has this aromatical rings.

That replacing the this carbon chain

here okay, and this actually create a small molecule

that is much much faster and specific to chelating calcium.

Indeed, the reason why Roger Tsien create BAPTA and

later is a lot of derivative is Roger Tsien wants to create

calcium indicator that can specially recognize calcium

to generate some signal changes.

For example, in the BAPTA condition if you measure

its absorption that with and without calcium,

you can see there's a spectral difference in terms of absorbance of calcium.

And we are going to further discuss a little bit later how this is more than

calcium indicators are derived from BAPTA and it's analog and

how does that revolutionize how we started the signalling or

second messengers including calcium in the life cells.

So that is a very important tool, okay?

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