WEBVTT

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We know from the last video that
if we have a high calcium

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ion concentration inside of the
muscle cell, those calcium

00:00:09.040 --> 00:00:13.500
ions will bond to the troponin
proteins which will then

00:00:13.500 --> 00:00:17.140
change their shape in such a way
that the tropomyosin will

00:00:17.140 --> 00:00:20.580
be moved out of the way and so
then the myosin heads can

00:00:20.580 --> 00:00:23.310
crawl along the actin filaments
and them we'll

00:00:23.310 --> 00:00:24.950
actually have muscle
contractions.

00:00:24.950 --> 00:00:29.140
So high calcium concentration,
or calcium ion concentration,

00:00:29.140 --> 00:00:30.850
we have contraction.

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Low calcium ion concentration,
these troponin proteins go to

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their standard confirmation and
they pull-- or you can say

00:00:39.060 --> 00:00:42.600
they move the tropomyosin back
in the way of the myosin

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heads-- and we have
no contraction.

00:00:53.750 --> 00:00:57.140
So the next obvious question
is, how does the muscle

00:00:57.140 --> 00:00:59.850
regulate whether we have high
calcium concentration and

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contraction or low calcium
concentration and relaxation?

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Or even a better question
is, how does the

00:01:04.940 --> 00:01:05.830
nervous system do it?

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How does the nervous system tell
the muscle to contract,

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to make its calcium
concentration high and

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contract or to make it
low again and relax?

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And to understand that, let's
do a little bit a review of

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what we learned on the
videos on neurons.

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Let me draw the terminal
junction of

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an axon right here.

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Instead of having a synapse
with a dendrite of another

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neuron, it's going to have
a synapse with an

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actual muscle cell.

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So this is its synapse with
the actual muscle cell.

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This is a synapse with an
actual muscle cell.

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Let me label everything just
so you don't get confused.

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This is the axon.

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We could call it the terminal
end of an axon.

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This is the synapse.

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Just a little terminology from
the neuron videos-- this space

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was a synaptic cleft.

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This is the presynaptic
neuron.

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This is-- I guess you could
kind of view it-- the

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post-synaptic cell.

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It's not a neuron
in this case.

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And then just so we
have-- this is our

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membrane of muscle cell.

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And I'm going to do-- probably
the next video or maybe a

00:02:32.540 --> 00:02:34.530
video after that, I'll actually
show you the anatomy

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of a muscle cell.

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In this, it'll be a little
abstract because we really

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want to understand how
the calcium ion

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concentration is regulated.

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This is called a sarcolemma.

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So this is the membrane
of the muscle cell.

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And this right here-- you could
imagine it's just a fold

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into the membrane of
the muscle cell.

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If I were to look at the surface
of the muscle cell,

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then it would look like a little
bit of a hole or an

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indentation that goes into the
cell, but here we did a cross

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section so you can imagine it
folding in, but if you poked

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it in with a needle or
something, this is

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what you would get.

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You would get a fold
in the membrane.

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And this right here is
called a T-tubule.

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And the T just stands
for transverse.

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It's going transverse to the
surface of the membrane.

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And over here-- and this is the
really important thing in

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this video, or the
really important

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organelle in this video.

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You have this organelle inside
of the muscle cell called the

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sarcoplasmic reticulum.

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And it actually is very similar
to an endoplasmic

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reticulum in somewhat of what
it is or maybe how it's

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related to an endoplasmic
reiticulum-- but here its main

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function is storage.

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While an endoplasmic reticulum,
it's involved in

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protein development and it has
ribosomes attached to it, but

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this is purely a storage
organelle.

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What the sarcoplasmic reticulum
does it has calcium

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ion pumps on its membrane and
what these do is they're ATP

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ases, which means that they
use ATP to fuel the pump.

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So you have ATP come in, ATP
attaches to it, and maybe a

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calcium ion will attach to it,
and when the ATP hydrolyzes

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into ADP plus a phosphate
group, that changes the

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confirmation of this protein
and it pumps

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the calcium ion in.

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So the calcium ions
get pumped in.

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So the net effect of all of
these calcium ion pumps on the

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membrane of the sarcoplasmic
reticulum is in a resting

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muscle, we'll have a very high
concentration of calcium ions

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on the inside.

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Now, I think you could
probably guess

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where this is going.

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When the muscle needs to
contract, these calcium ions

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get dumped out into the
cytoplasm of the cell.

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And then they're able to bond
to the troponin right here,

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and do everything we talked
about in the last video.

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So what we care about is, just
how does it know when to dump

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its calcium ions into the
rest of the cell?

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This is the inside
of the cell.

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And so this area is what the
actin filaments and the myosin

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heads and all of the rest,
and the troponin, and the

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tropomyosin-- they're all
exposed to the environment

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that is over here.

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So you can imagine-- I could
just draw it here

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just to make it clear.

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I'm drawing it very abstract.

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We'll see more of the structure
in a future video.

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This is a very abstract drawing,
but I think this'll

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give you a sense of
what's going on.

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So let's say this neuron-- and
we'll call this a motor

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neuron-- it's signaling for
a muscle contraction.

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So first of all, we know how
signals travel across neurons,

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especially across axons with
an action potential.

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We could have a sodium
channel right here.

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It's voltage gated so you have
a little bit of a positive

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voltage there.

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That tells this voltage gated
sodium channel to open up.

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So it opens up and allows even
more of the sodium to flow in.

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That makes it a little bit
more positive here.

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So then that triggers the next
voltage gated channel to open

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up-- and so it keeps traveling
down the membrane of the

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axon-- and eventually, when you
get enough of a positive

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threshold, voltage gated calcium
channels open up.

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This is all a review
of what we learned

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in the neuron videos.

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So eventually, when it gets
positive enough close to these

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calcium ion channels, they
allow the calcium

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ions to flow in.

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And the calcium ions flow in and
they bond to those special

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proteins near the synaptic
membrane or the presynaptic

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membrane right there.

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These are calcium ions.

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They bond to proteins that
were docking vesicles.

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Remember, vesicles were just
these membranes around

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neurotransmitters.

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When the calcium binds to those
proteins, it allows

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exocytosis to occur.

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It allows the membrane of the
vesicles to merge with the

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membrane of the actual
neuron and the

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contents get dumped out.

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This is all review from
the neuron videos.

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I explained it in much more
detail in those videos, but

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you have-- all of these

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neurotransmitters get dumped out.

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And we were talking about the
synapse between a neuron and a

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muscle cell.

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The neurotransmitter
here is acetylcholine.

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But just like what would happen
at a dendrite, the

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acetylcholine binds to receptors
on the sarcolemma or

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the membrane of the muscle cell
and that opens sodium

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channels on the muscle cell.

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So the muscle cell also has a a
voltage gradient across its

00:09:02.330 --> 00:09:07.210
membrane, just like
a neuron does.

00:09:07.210 --> 00:09:11.150
So when this guy gets some
acetylcholene, it allows

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sodium to flow inside
the muscle cell.

00:09:16.240 --> 00:09:18.580
So you have a plus there and
that causes an action

00:09:18.580 --> 00:09:19.990
potential in the muscle cell.

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So then you have a little bit
of a positive charge.

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If it gets high enough to a
threshold level, it'll trigger

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this voltage gated channel right
here, which will allow

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more sodium to flow in.

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So it'll become a little
bit positive over here.

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Of course, it also has potassium
to reverse it.

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It's just like what's going
on in a neuron.

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So eventually this action
potential-- you have a sodium

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channel over here.

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It gets a little bit positive.

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When it gets enough positive,
then it opens up and allows

00:09:47.710 --> 00:09:49.750
even more sodium to flow in.

00:09:49.750 --> 00:09:51.250
So you have this action
potential.

00:09:51.250 --> 00:09:53.230
and then that action potential--
so you have a

00:09:53.230 --> 00:09:57.950
sodium channel over here-- it
goes down this T-tubule.

00:09:57.950 --> 00:10:00.230
So the information from the
neuron-- you could imagine the

00:10:00.230 --> 00:10:03.930
action potential then turns into
kind of a chemical signal

00:10:03.930 --> 00:10:06.370
which triggers another
action potential that

00:10:06.370 --> 00:10:07.880
goes down the T-tubule.

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And this is the interesting
part-- and actually this is an

00:10:10.560 --> 00:10:13.670
area of open research right
now and I'll give you some

00:10:13.670 --> 00:10:17.860
leads if you want to read more
about this research-- is that

00:10:17.860 --> 00:10:20.940
you have a protein complex that
essentially bridges the

00:10:20.940 --> 00:10:23.010
sarcoplasmic reticulum
to the T-tubule.

00:10:23.010 --> 00:10:28.600
And I'll just draw it as
a big box right here.

00:10:28.600 --> 00:10:31.180
So you have this protein
complex right there.

00:10:31.180 --> 00:10:34.970
And I'll actually show it--
people believe-- I'll sort

00:10:34.970 --> 00:10:36.270
some words out here.

00:10:36.270 --> 00:10:44.170
It involves the proteins
triadin, junctin,

00:10:44.170 --> 00:10:51.180
calsequestrin, and ryanodine.

00:10:56.290 --> 00:10:59.550
But they're somehow involved in
a protein complex here that

00:10:59.550 --> 00:11:04.550
bridges between the T-tubule the
sarcoplasmic verticulum,

00:11:04.550 --> 00:11:06.720
but the big picture is what
happens when this action

00:11:06.720 --> 00:11:09.880
potential travels down here--
so we get positive enough

00:11:09.880 --> 00:11:16.280
right around here, this complex
of proteins triggers

00:11:16.280 --> 00:11:17.610
the release of calcium.

00:11:17.610 --> 00:11:20.920
And they think that the
ryanodine is actually the part

00:11:20.920 --> 00:11:23.930
that actually releases the
calcium, but we could just say

00:11:23.930 --> 00:11:27.790
that it-- maybe it's triggered
right here.

00:11:27.790 --> 00:11:30.330
When the action potential
travels down-- let me switch

00:11:30.330 --> 00:11:31.010
to another color.

00:11:31.010 --> 00:11:33.100
I'm using this purple
too much.

00:11:33.100 --> 00:11:36.980
When the action potential gets
far enough-- I'll use red

00:11:36.980 --> 00:11:40.070
right here-- when the action
potential gets far enough-- so

00:11:40.070 --> 00:11:42.260
this environment gets a little
positive with all those sodium

00:11:42.260 --> 00:11:45.920
ions flowing in, this mystery
box-- and you could do web

00:11:45.920 --> 00:11:47.100
searches for these proteins.

00:11:47.100 --> 00:11:49.030
People are still trying to
understand exactly how this

00:11:49.030 --> 00:11:52.570
mystery box works-- it triggers
an opening for all of

00:11:52.570 --> 00:11:57.290
these calcium ions to escape
the sarcoplasmic reticulum.

00:11:57.290 --> 00:12:03.870
So then all these calcium ions
get dumped into the outside of

00:12:03.870 --> 00:12:07.610
the sarcoplasmic reticulum
into-- just the inside of the

00:12:07.610 --> 00:12:10.230
cell, into the cytoplasm
of the cell.

00:12:10.230 --> 00:12:12.550
Now when that happens, what's
doing to happen?

00:12:12.550 --> 00:12:14.670
Well, the high calcium
concentration, the calcium

00:12:14.670 --> 00:12:17.390
ions bond to the troponin, just
like what we said at the

00:12:17.390 --> 00:12:18.750
beginning of the video.

00:12:18.750 --> 00:12:23.390
The calcium ions bond to the
troponin, move the tropomyosin

00:12:23.390 --> 00:12:26.520
out of the way, and then the
myosin using ATP like we

00:12:26.520 --> 00:12:30.050
learned two videos ago can start
crawling up the actin--

00:12:30.050 --> 00:12:35.030
and at the same time, once the
signal disappears, this thing

00:12:35.030 --> 00:12:39.290
shuts down and then these
calcium ion pumps will reduce

00:12:39.290 --> 00:12:41.180
the calcium ion concentration
again.

00:12:41.180 --> 00:12:45.070
And then our contraction will
stop and the muscle will get

00:12:45.070 --> 00:12:46.090
relaxed again.

00:12:46.090 --> 00:12:49.070
So the whole big thing here is
that we have this container of

00:12:49.070 --> 00:12:52.440
calcium ions that, when the
muscles relax, is essentially

00:12:52.440 --> 00:12:55.330
taking the calcium ions out of
the inside of the cell so the

00:12:55.330 --> 00:12:58.830
muscle is relaxed so that you
can't have your myosin climb

00:12:58.830 --> 00:13:00.330
up the actin.

00:13:00.330 --> 00:13:03.190
But then when it gets the
signal, it dumps it back in

00:13:03.190 --> 00:13:06.040
and then we actually have a
muscle contraction because the

00:13:06.040 --> 00:13:11.280
tropomyosin gets moved out of
the way by the troponin., So I

00:13:11.280 --> 00:13:12.090
don't know.
That's pretty fascinating.

00:13:12.090 --> 00:13:14.160
It's actually even fascinating
that this is still not

00:13:14.160 --> 00:13:16.200
completely well understood.

00:13:16.200 --> 00:13:19.140
This is an active-- if you want
to become a biological

00:13:19.140 --> 00:13:21.360
researcher, this could be an
interesting thing to try to

00:13:21.360 --> 00:13:22.330
understand.

00:13:22.330 --> 00:13:25.740
One, it's interesting just from
a scientific point of

00:13:25.740 --> 00:13:27.900
view of how this actually
functions, but there's

00:13:27.900 --> 00:13:31.630
actually-- there's maybe
potential diseases that are

00:13:31.630 --> 00:13:34.210
byproducts of malfunctioning
proteins right here.

00:13:34.210 --> 00:13:37.050
Maybe you can somehow make these
things perform better or

00:13:37.050 --> 00:13:37.770
worse, or who knows.

00:13:37.770 --> 00:13:41.960
So there actually are positive
impacts that you could have if

00:13:41.960 --> 00:13:44.750
you actually figured out what
exactly is going on here when

00:13:44.750 --> 00:13:47.440
the action potential
shows up to open up

00:13:47.440 --> 00:13:48.490
this calcium channel.

00:13:48.490 --> 00:13:49.770
So now we have the
big picture.

00:13:49.770 --> 00:13:53.770
We know how a motor neuron can
stimulate a contraction of a

00:13:53.770 --> 00:14:00.240
cell by allowing the
sarcoplasmic reticulum to

00:14:00.240 --> 00:14:03.490
allow calcium ions to travel
across this membrane in the

00:14:03.490 --> 00:14:04.590
cytoplasm of the cell.

00:14:04.590 --> 00:14:07.240
And I was doing a little bit of
reading before this video.

00:14:07.240 --> 00:14:08.740
These pumps are very
efficient.

00:14:08.740 --> 00:14:11.980
So once the signal goes away and
this door is closed right

00:14:11.980 --> 00:14:16.900
here, this this sarcoplasmic
reticulum can get back the ion

00:14:16.900 --> 00:14:19.070
concentration in about
30 milliseconds.

00:14:19.070 --> 00:14:22.100
So that's why we're so good at
stopping contractions, why I

00:14:22.100 --> 00:14:25.820
can punch and then pull back my
arm and then have it relax

00:14:25.820 --> 00:14:28.870
all within split-seconds
because we can stop the

00:14:28.870 --> 00:14:33.520
contraction in 30 milliseconds,
which is less

00:14:33.520 --> 00:14:34.670
than 1/30 of a second.

00:14:34.670 --> 00:14:37.500
So anyway, I'll see in the next
video, where we'll study

00:14:37.500 --> 00:14:40.030
the actual anatomy of
a muscle cell in a

00:14:40.030 --> 00:14:41.840
little bit more detail.