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!
6.4 Ion channel, membrane potential and synaptic transmission I
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来自 Peking University 的课程
Advanced Neurobiology I
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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
Now we already have the crystal structure of some of those ion channels, and
it's very beautiful structures if you take a look.
And now we move along trying to switch gear from the provocation of
action potential to the communication in between the neurons
that is the so-called synaptic transmission, okay?
The outline will be that the action potential, or
the Hodgkin-Huxley model, largely satisfactory
explained the electrical signal propagation.
We send a [INAUDIBLE] through that axial into the nerve terminal.
Okay, that is always [INAUDIBLE] or massive.
And now we are going to concentrate on to the signal between two neurons.
Okay, that's the synapse transmission.
Okay, and this is the outline the action potential propagation and
then synapse transmission, especially the essential
roles of calcium ions and how that triggers the transmitter release.
And what is our current understanding
of the molecular mechanism of transmitter release?
As larger medical complex work together to
mediate the discharge of transmitter through the presynaptic terminals, okay?
And if we still think about the action potential provocation,
that is we never activation of wattage gated sodium channel.
And it will generate, the current that it will charge
the axon membrane of this neuron.
And it's a charge because axon of
cell membrane can be single as a capacitance that can start charge.
Once it start charge, it's going to change its membrane potential.
So if we look at this passive membrane potential distribution.
If you have a single source, current source injecting current source here and
you expect that this membrane wattage will decay over distance.
Okay?
But we see this threshold at this region,
that if we reach this threshold that it can further activate the voltage gated
sodium channel to charge this membrane again to generate action potential.
So that's how the action potential can be propagate from
one point source to the rest by continuously
charge the adjacent membrane to reach their threshold.
And then keep going until it reaches into the nuff terminal.
So this reflects how the current charge and spread across the membrane.
Okay for certain axiom, they have wrapping
strong cells that has the marinated sheet.
Okay so in that case the action potential seen can be
travel even faster because of it has a lot of capacitance they don't need to charge.
They simply just need to charge the other part in the Ranvier's node.
So the action potential travel can be faster.
Once you travel to the nerve terminal then you will
actuate the target.
So, this is one of the simplest
nerve circuit in our body, okay?
For example, in this muscle, and if you stretch it,
then this muscle can lead to the reflex of another muscle.
And how does that work?
Well, it's well understood now.
Once stretching this muscle, we'll activate some
mechanical sensory organ, the muscle spindle.
The muscle spindle will generate
the receptor potential in sensory neurons, okay.
So the sensory neurons will have the, in the terminals,
will assist the stretching of the muscle spindle.
And then generate electrical potential changes.
And if the electrical potential changes are surpassing,
or are going beyond, the threshold for action potential.
Then what happen is, that we are going to generate action potential in
that sensory neuron, which will propagate into
the nerve terminal For this sensory neuron.
And this sensory neuron's nerve terminal is in the spinal cord, okay?
And it will release some transmitter, for example, glutamine
that will excite the downstream motor neuron, okay?
And this motor neuron once the, since the reduce of transmitter,
because the glutamine is exciting neurotransmitter.
It's sensing will make this [INAUDIBLE] neuron
to be more exciteful, to depolarize.
To the pore is downgraded potential.
Okay, and if downgraded potential reaches it's threshold to become action potential.
Again, action potential will self sufficient to charge and
discharge this axial membrane to propagate.
And propagate jumping In this
[INAUDIBLE] note, so [INAUDIBLE] faster.
And then it which enter the nerve terminal again that it will lead to that release of
yet another transmitter in our human body this will be as to [INAUDIBLE].
And that will intent release and
activate the receptors in the muscle which
is the receptor okay.
Is the one of the sub ties is called nicotinic like acetylcholine receptor.
And that will mediate.
The excitation of this muscle and lead to eventually the muscle contraction, okay?
So in one of the simplest circuit,
you have the communications between neurons and its target muscle.
A muscle is, a lot of times, are the common final destination.
The effects us that will execute the function,
either closing your eyes, or stretching your arms.
Okay?
That all rely on the muscle.
Okay? And then,
we want to understand, how's the transmitter
get released from a nerve terminal, form a presynaptic nerve terminal.
And how does it activate a post-nerve neuron?
Because that is the most essential part.
In fact, that is probably the fundamental unique property of neuron.
Comparing with the rest of the cell.
But it has this sophisticated machinery to deal with the action potential into
the [INAUDIBLE] terminal to turn into action potential [INAUDIBLE] membrane.
And then lead to the transmitter release.
And then subsequent activate a post packet for example and not a neuron.
Again, so the last 50 years study we already
have a pretty good understanding of that process.
For example, we know, for the central nervous system,
the action potential generation that the open and close of
sodium potassium channels will travel to the nerve terminal.
And where you have the action potential comes here you would
the membrane in the nerve terminal.
Okay, and then this depolarization of membrane potential
near the plasma membrane of [INAUDIBLE] terminal will activate.
Yet another special type of ion channel which is
well educated Is seductive to calcium.
So you will allow calcium influx from the cell into the nerve terminal.
And this calcium influx will lead to
the fusion of the pre-synaptic in reach,
so-called synaptic vesicals.
These synaptic vesicals are food of neurotransmitters.
Are in reach with neurotransmitters.
And once they fuse with the help of calcium and
additional protein machineries.
Then these transmitters will diffuse mostly passively
will diffuse into the synaptic cleft.
And then will bind to the postsynaptic receptor in our central brain
The majority of the ones at the glutamate receptors.
For example, receptor.
And then this ion channel receive to the transmitter.
It will open.
And this open will allow it positive ions,
like sodium, to come to this cell again to
depolarize these postsynaptic cells, okay?
So this process is
what is our current understanding of this chemical synaptic transmission.
That is the propagation of wattage changes with the 85 action potentials.
Get converted into the chemical signal.
The calcium influx, and then the transmitter released, and
then get converted back into the electrical signal again, okay?
And now we are interested about, how do we know?
How do we know it's calcium that's playing an important role?
And we have seen some [INAUDIBLE] like protein here, where are they?
How do you find and out, okay.
And if you find out, how do you proof.
They indeed the essential machinery to immediate transfer to release, okay.
And once they release, how do you know which
receptor will sense for example in this case the glutamate release.
If you are in the 1980s,
none of this glutamate receptor, this molecular identity has been identified.
How will you identify them?
What will be your approach to find
out that they are the receptor
molecule to that and how do you know if you identify it?
What is the molecular basis?
What is the structural basis that it will sense glutamate.
And then, how could this glutamate sensing, which is ligand binding,
control the opening of this ion channel.
You are bias to a small molecule, right?
Glutamate.
It's ubiquitous.
It's one of the essential amino acids.
How could that lead to a open of the ion channel?
What is the molecular basis?
And why it will be selectively only for
sodium or positive ions, not for negative ions.
What is that medical basis?
So this will be part of our effort,
our journey to find.
Even though the status
in the last 50 years has established this dogma.
Established this quite universal models of his chemicals in that transmission.
Transmitter release pure SIDS by post naval receptors.
Electrical signals get converted into chemical signals and get converted back.
But if you are traveling back 50 years ago or to 60 years ago.
In their time how to look to experiments to prove or disprove this.
So that would our main agenda.
So we're essentially time travel back.
Okay.
Fast backwards to the in the 70 years ago.
How will you know?
First as we said, the action potential propagated into the nerve terminal,
and then the calcium influx that can lead to the transmitter is.
All right, now let's come travel back to 70 years ago.
You guys are good, because we are traveling back, and
we still have the knowledge of modern technology, right?
It's okay.
We just travel back with our modern knowledge and equipment.
We can carry on with you.
How do you design an experiment to prove that the calcium
indeed is important for radiate transmitter release.
How?
