1
00:00:00,750 --> 00:00:04,480
We know from the last video that
if we have a high calcium

2
00:00:04,480 --> 00:00:09,040
ion concentration inside of the
muscle cell, those calcium

3
00:00:09,040 --> 00:00:13,500
ions will bond to the troponin
proteins which will then

4
00:00:13,500 --> 00:00:17,140
change their shape in such a way
that the tropomyosin will

5
00:00:17,140 --> 00:00:20,580
be moved out of the way and so
then the myosin heads can

6
00:00:20,580 --> 00:00:23,310
crawl along the actin filaments
and them we'll

7
00:00:23,310 --> 00:00:24,950
actually have muscle
contractions.

8
00:00:24,950 --> 00:00:29,140
So high calcium concentration,
or calcium ion concentration,

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00:00:29,140 --> 00:00:30,850
we have contraction.

10
00:00:30,850 --> 00:00:35,560
Low calcium ion concentration,
these troponin proteins go to

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00:00:35,560 --> 00:00:39,060
their standard confirmation and
they pull-- or you can say

12
00:00:39,060 --> 00:00:42,600
they move the tropomyosin back
in the way of the myosin

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00:00:42,600 --> 00:00:44,165
heads-- and we have
no contraction.

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00:00:53,750 --> 00:00:57,140
So the next obvious question
is, how does the muscle

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00:00:57,140 --> 00:00:59,850
regulate whether we have high
calcium concentration and

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00:00:59,850 --> 00:01:03,350
contraction or low calcium
concentration and relaxation?

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00:01:03,350 --> 00:01:04,940
Or even a better question
is, how does the

18
00:01:04,940 --> 00:01:05,830
nervous system do it?

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00:01:05,830 --> 00:01:09,490
How does the nervous system tell
the muscle to contract,

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00:01:09,490 --> 00:01:11,550
to make its calcium
concentration high and

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00:01:11,550 --> 00:01:14,010
contract or to make it
low again and relax?

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00:01:14,010 --> 00:01:17,900
And to understand that, let's
do a little bit a review of

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00:01:17,900 --> 00:01:20,790
what we learned on the
videos on neurons.

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00:01:20,790 --> 00:01:24,000
Let me draw the terminal
junction of

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00:01:24,000 --> 00:01:27,500
an axon right here.

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00:01:27,500 --> 00:01:30,540
Instead of having a synapse
with a dendrite of another

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00:01:30,540 --> 00:01:32,890
neuron, it's going to have
a synapse with an

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00:01:32,890 --> 00:01:35,130
actual muscle cell.

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00:01:35,130 --> 00:01:37,145
So this is its synapse with
the actual muscle cell.

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00:01:44,420 --> 00:01:47,170
This is a synapse with an
actual muscle cell.

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00:01:47,170 --> 00:01:50,070
Let me label everything just
so you don't get confused.

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00:01:50,070 --> 00:01:51,470
This is the axon.

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00:01:51,470 --> 00:01:53,470
We could call it the terminal
end of an axon.

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00:01:57,610 --> 00:01:58,860
This is the synapse.

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00:02:05,440 --> 00:02:08,150
Just a little terminology from
the neuron videos-- this space

36
00:02:08,150 --> 00:02:10,210
was a synaptic cleft.

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00:02:10,210 --> 00:02:13,650
This is the presynaptic
neuron.

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00:02:13,650 --> 00:02:15,430
This is-- I guess you could
kind of view it-- the

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00:02:15,430 --> 00:02:16,830
post-synaptic cell.

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00:02:16,830 --> 00:02:19,050
It's not a neuron
in this case.

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00:02:19,050 --> 00:02:21,090
And then just so we
have-- this is our

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00:02:21,090 --> 00:02:30,240
membrane of muscle cell.

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00:02:30,240 --> 00:02:32,540
And I'm going to do-- probably
the next video or maybe a

44
00:02:32,540 --> 00:02:34,530
video after that, I'll actually
show you the anatomy

45
00:02:34,530 --> 00:02:35,610
of a muscle cell.

46
00:02:35,610 --> 00:02:37,230
In this, it'll be a little
abstract because we really

47
00:02:37,230 --> 00:02:39,300
want to understand how
the calcium ion

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00:02:39,300 --> 00:02:42,810
concentration is regulated.

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00:02:42,810 --> 00:02:44,060
This is called a sarcolemma.

50
00:02:53,580 --> 00:02:56,120
So this is the membrane
of the muscle cell.

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00:02:56,120 --> 00:02:59,070
And this right here-- you could
imagine it's just a fold

52
00:02:59,070 --> 00:03:00,980
into the membrane of
the muscle cell.

53
00:03:00,980 --> 00:03:04,000
If I were to look at the surface
of the muscle cell,

54
00:03:04,000 --> 00:03:05,850
then it would look like a little
bit of a hole or an

55
00:03:05,850 --> 00:03:09,040
indentation that goes into the
cell, but here we did a cross

56
00:03:09,040 --> 00:03:14,000
section so you can imagine it
folding in, but if you poked

57
00:03:14,000 --> 00:03:16,590
it in with a needle or
something, this is

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00:03:16,590 --> 00:03:17,240
what you would get.

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00:03:17,240 --> 00:03:19,100
You would get a fold
in the membrane.

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00:03:19,100 --> 00:03:20,460
And this right here is
called a T-tubule.

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00:03:26,360 --> 00:03:28,100
And the T just stands
for transverse.

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00:03:28,100 --> 00:03:31,720
It's going transverse to the
surface of the membrane.

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00:03:31,720 --> 00:03:35,060
And over here-- and this is the
really important thing in

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00:03:35,060 --> 00:03:36,560
this video, or the
really important

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00:03:36,560 --> 00:03:37,520
organelle in this video.

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00:03:37,520 --> 00:03:42,410
You have this organelle inside
of the muscle cell called the

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00:03:42,410 --> 00:03:43,890
sarcoplasmic reticulum.

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00:03:54,740 --> 00:03:57,700
And it actually is very similar
to an endoplasmic

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00:03:57,700 --> 00:04:03,180
reticulum in somewhat of what
it is or maybe how it's

70
00:04:03,180 --> 00:04:06,750
related to an endoplasmic
reiticulum-- but here its main

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00:04:06,750 --> 00:04:07,760
function is storage.

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00:04:07,760 --> 00:04:10,400
While an endoplasmic reticulum,
it's involved in

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00:04:10,400 --> 00:04:14,470
protein development and it has
ribosomes attached to it, but

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00:04:14,470 --> 00:04:18,860
this is purely a storage
organelle.

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00:04:18,860 --> 00:04:22,500
What the sarcoplasmic reticulum
does it has calcium

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00:04:22,500 --> 00:04:32,920
ion pumps on its membrane and
what these do is they're ATP

77
00:04:32,920 --> 00:04:37,530
ases, which means that they
use ATP to fuel the pump.

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00:04:37,530 --> 00:04:42,450
So you have ATP come in, ATP
attaches to it, and maybe a

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00:04:42,450 --> 00:04:52,620
calcium ion will attach to it,
and when the ATP hydrolyzes

80
00:04:52,620 --> 00:05:01,470
into ADP plus a phosphate
group, that changes the

81
00:05:01,470 --> 00:05:04,140
confirmation of this protein
and it pumps

82
00:05:04,140 --> 00:05:05,700
the calcium ion in.

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00:05:05,700 --> 00:05:08,230
So the calcium ions
get pumped in.

84
00:05:08,230 --> 00:05:12,610
So the net effect of all of
these calcium ion pumps on the

85
00:05:12,610 --> 00:05:16,540
membrane of the sarcoplasmic
reticulum is in a resting

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00:05:16,540 --> 00:05:20,700
muscle, we'll have a very high
concentration of calcium ions

87
00:05:20,700 --> 00:05:21,950
on the inside.

88
00:05:26,630 --> 00:05:28,570
Now, I think you could
probably guess

89
00:05:28,570 --> 00:05:29,980
where this is going.

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00:05:29,980 --> 00:05:33,010
When the muscle needs to
contract, these calcium ions

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00:05:33,010 --> 00:05:37,320
get dumped out into the
cytoplasm of the cell.

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00:05:37,320 --> 00:05:42,610
And then they're able to bond
to the troponin right here,

93
00:05:42,610 --> 00:05:45,120
and do everything we talked
about in the last video.

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00:05:45,120 --> 00:05:49,180
So what we care about is, just
how does it know when to dump

95
00:05:49,180 --> 00:05:51,760
its calcium ions into the
rest of the cell?

96
00:05:51,760 --> 00:05:53,140
This is the inside
of the cell.

97
00:06:00,370 --> 00:06:06,360
And so this area is what the
actin filaments and the myosin

98
00:06:06,360 --> 00:06:09,350
heads and all of the rest,
and the troponin, and the

99
00:06:09,350 --> 00:06:12,230
tropomyosin-- they're all
exposed to the environment

100
00:06:12,230 --> 00:06:13,320
that is over here.

101
00:06:13,320 --> 00:06:15,280
So you can imagine-- I could
just draw it here

102
00:06:15,280 --> 00:06:16,530
just to make it clear.

103
00:06:21,480 --> 00:06:22,690
I'm drawing it very abstract.

104
00:06:22,690 --> 00:06:24,480
We'll see more of the structure
in a future video.

105
00:06:38,650 --> 00:06:40,870
This is a very abstract drawing,
but I think this'll

106
00:06:40,870 --> 00:06:42,650
give you a sense of
what's going on.

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00:06:42,650 --> 00:06:45,510
So let's say this neuron-- and
we'll call this a motor

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00:06:45,510 --> 00:06:54,380
neuron-- it's signaling for
a muscle contraction.

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00:06:54,380 --> 00:06:57,610
So first of all, we know how
signals travel across neurons,

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00:06:57,610 --> 00:07:01,100
especially across axons with
an action potential.

111
00:07:01,100 --> 00:07:04,460
We could have a sodium
channel right here.

112
00:07:04,460 --> 00:07:07,410
It's voltage gated so you have
a little bit of a positive

113
00:07:07,410 --> 00:07:08,500
voltage there.

114
00:07:08,500 --> 00:07:12,420
That tells this voltage gated
sodium channel to open up.

115
00:07:12,420 --> 00:07:16,160
So it opens up and allows even
more of the sodium to flow in.

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00:07:16,160 --> 00:07:18,340
That makes it a little bit
more positive here.

117
00:07:18,340 --> 00:07:21,880
So then that triggers the next
voltage gated channel to open

118
00:07:21,880 --> 00:07:25,010
up-- and so it keeps traveling
down the membrane of the

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00:07:25,010 --> 00:07:28,410
axon-- and eventually, when you
get enough of a positive

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00:07:28,410 --> 00:07:32,590
threshold, voltage gated calcium
channels open up.

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00:07:36,060 --> 00:07:37,680
This is all a review
of what we learned

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00:07:37,680 --> 00:07:39,740
in the neuron videos.

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00:07:39,740 --> 00:07:41,760
So eventually, when it gets
positive enough close to these

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00:07:41,760 --> 00:07:44,290
calcium ion channels, they
allow the calcium

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00:07:44,290 --> 00:07:46,300
ions to flow in.

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00:07:46,300 --> 00:07:50,060
And the calcium ions flow in and
they bond to those special

127
00:07:50,060 --> 00:07:53,950
proteins near the synaptic
membrane or the presynaptic

128
00:07:53,950 --> 00:07:54,850
membrane right there.

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00:07:54,850 --> 00:07:56,010
These are calcium ions.

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00:07:56,010 --> 00:08:00,990
They bond to proteins that
were docking vesicles.

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00:08:00,990 --> 00:08:08,170
Remember, vesicles were just
these membranes around

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00:08:08,170 --> 00:08:09,420
neurotransmitters.

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00:08:13,250 --> 00:08:17,500
When the calcium binds to those
proteins, it allows

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00:08:17,500 --> 00:08:18,840
exocytosis to occur.

135
00:08:18,840 --> 00:08:22,850
It allows the membrane of the
vesicles to merge with the

136
00:08:22,850 --> 00:08:25,190
membrane of the actual
neuron and the

137
00:08:25,190 --> 00:08:26,600
contents get dumped out.

138
00:08:26,600 --> 00:08:28,670
This is all review from
the neuron videos.

139
00:08:28,670 --> 00:08:31,470
I explained it in much more
detail in those videos, but

140
00:08:31,470 --> 00:08:32,490
you have-- all of these

141
00:08:32,490 --> 00:08:34,500
neurotransmitters get dumped out.

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00:08:34,500 --> 00:08:38,809
And we were talking about the
synapse between a neuron and a

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00:08:38,809 --> 00:08:39,450
muscle cell.

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00:08:39,450 --> 00:08:41,059
The neurotransmitter
here is acetylcholine.

145
00:08:47,130 --> 00:08:49,320
But just like what would happen
at a dendrite, the

146
00:08:49,320 --> 00:08:53,990
acetylcholine binds to receptors
on the sarcolemma or

147
00:08:53,990 --> 00:08:57,410
the membrane of the muscle cell
and that opens sodium

148
00:08:57,410 --> 00:08:58,820
channels on the muscle cell.

149
00:08:58,820 --> 00:09:02,330
So the muscle cell also has a a
voltage gradient across its

150
00:09:02,330 --> 00:09:07,210
membrane, just like
a neuron does.

151
00:09:07,210 --> 00:09:11,150
So when this guy gets some
acetylcholene, it allows

152
00:09:11,150 --> 00:09:16,240
sodium to flow inside
the muscle cell.

153
00:09:16,240 --> 00:09:18,580
So you have a plus there and
that causes an action

154
00:09:18,580 --> 00:09:19,990
potential in the muscle cell.

155
00:09:19,990 --> 00:09:22,510
So then you have a little bit
of a positive charge.

156
00:09:22,510 --> 00:09:26,680
If it gets high enough to a
threshold level, it'll trigger

157
00:09:26,680 --> 00:09:29,100
this voltage gated channel right
here, which will allow

158
00:09:29,100 --> 00:09:32,380
more sodium to flow in.

159
00:09:32,380 --> 00:09:35,080
So it'll become a little
bit positive over here.

160
00:09:35,080 --> 00:09:37,035
Of course, it also has potassium
to reverse it.

161
00:09:37,035 --> 00:09:38,870
It's just like what's going
on in a neuron.

162
00:09:38,870 --> 00:09:41,970
So eventually this action
potential-- you have a sodium

163
00:09:41,970 --> 00:09:43,170
channel over here.

164
00:09:43,170 --> 00:09:44,780
It gets a little bit positive.

165
00:09:44,780 --> 00:09:47,710
When it gets enough positive,
then it opens up and allows

166
00:09:47,710 --> 00:09:49,750
even more sodium to flow in.

167
00:09:49,750 --> 00:09:51,250
So you have this action
potential.

168
00:09:51,250 --> 00:09:53,230
and then that action potential--
so you have a

169
00:09:53,230 --> 00:09:57,950
sodium channel over here-- it
goes down this T-tubule.

170
00:09:57,950 --> 00:10:00,230
So the information from the
neuron-- you could imagine the

171
00:10:00,230 --> 00:10:03,930
action potential then turns into
kind of a chemical signal

172
00:10:03,930 --> 00:10:06,370
which triggers another
action potential that

173
00:10:06,370 --> 00:10:07,880
goes down the T-tubule.

174
00:10:07,880 --> 00:10:10,560
And this is the interesting
part-- and actually this is an

175
00:10:10,560 --> 00:10:13,670
area of open research right
now and I'll give you some

176
00:10:13,670 --> 00:10:17,860
leads if you want to read more
about this research-- is that

177
00:10:17,860 --> 00:10:20,940
you have a protein complex that
essentially bridges the

178
00:10:20,940 --> 00:10:23,010
sarcoplasmic reticulum
to the T-tubule.

179
00:10:23,010 --> 00:10:28,600
And I'll just draw it as
a big box right here.

180
00:10:28,600 --> 00:10:31,180
So you have this protein
complex right there.

181
00:10:31,180 --> 00:10:34,970
And I'll actually show it--
people believe-- I'll sort

182
00:10:34,970 --> 00:10:36,270
some words out here.

183
00:10:36,270 --> 00:10:44,170
It involves the proteins
triadin, junctin,

184
00:10:44,170 --> 00:10:51,180
calsequestrin, and ryanodine.

185
00:10:56,290 --> 00:10:59,550
But they're somehow involved in
a protein complex here that

186
00:10:59,550 --> 00:11:04,550
bridges between the T-tubule the
sarcoplasmic verticulum,

187
00:11:04,550 --> 00:11:06,720
but the big picture is what
happens when this action

188
00:11:06,720 --> 00:11:09,880
potential travels down here--
so we get positive enough

189
00:11:09,880 --> 00:11:16,280
right around here, this complex
of proteins triggers

190
00:11:16,280 --> 00:11:17,610
the release of calcium.

191
00:11:17,610 --> 00:11:20,920
And they think that the
ryanodine is actually the part

192
00:11:20,920 --> 00:11:23,930
that actually releases the
calcium, but we could just say

193
00:11:23,930 --> 00:11:27,790
that it-- maybe it's triggered
right here.

194
00:11:27,790 --> 00:11:30,330
When the action potential
travels down-- let me switch

195
00:11:30,330 --> 00:11:31,010
to another color.

196
00:11:31,010 --> 00:11:33,100
I'm using this purple
too much.

197
00:11:33,100 --> 00:11:36,980
When the action potential gets
far enough-- I'll use red

198
00:11:36,980 --> 00:11:40,070
right here-- when the action
potential gets far enough-- so

199
00:11:40,070 --> 00:11:42,260
this environment gets a little
positive with all those sodium

200
00:11:42,260 --> 00:11:45,920
ions flowing in, this mystery
box-- and you could do web

201
00:11:45,920 --> 00:11:47,100
searches for these proteins.

202
00:11:47,100 --> 00:11:49,030
People are still trying to
understand exactly how this

203
00:11:49,030 --> 00:11:52,570
mystery box works-- it triggers
an opening for all of

204
00:11:52,570 --> 00:11:57,290
these calcium ions to escape
the sarcoplasmic reticulum.

205
00:11:57,290 --> 00:12:03,870
So then all these calcium ions
get dumped into the outside of

206
00:12:03,870 --> 00:12:07,610
the sarcoplasmic reticulum
into-- just the inside of the

207
00:12:07,610 --> 00:12:10,230
cell, into the cytoplasm
of the cell.

208
00:12:10,230 --> 00:12:12,550
Now when that happens, what's
doing to happen?

209
00:12:12,550 --> 00:12:14,670
Well, the high calcium
concentration, the calcium

210
00:12:14,670 --> 00:12:17,390
ions bond to the troponin, just
like what we said at the

211
00:12:17,390 --> 00:12:18,750
beginning of the video.

212
00:12:18,750 --> 00:12:23,390
The calcium ions bond to the
troponin, move the tropomyosin

213
00:12:23,390 --> 00:12:26,520
out of the way, and then the
myosin using ATP like we

214
00:12:26,520 --> 00:12:30,050
learned two videos ago can start
crawling up the actin--

215
00:12:30,050 --> 00:12:35,030
and at the same time, once the
signal disappears, this thing

216
00:12:35,030 --> 00:12:39,290
shuts down and then these
calcium ion pumps will reduce

217
00:12:39,290 --> 00:12:41,180
the calcium ion concentration
again.

218
00:12:41,180 --> 00:12:45,070
And then our contraction will
stop and the muscle will get

219
00:12:45,070 --> 00:12:46,090
relaxed again.

220
00:12:46,090 --> 00:12:49,070
So the whole big thing here is
that we have this container of

221
00:12:49,070 --> 00:12:52,440
calcium ions that, when the
muscles relax, is essentially

222
00:12:52,440 --> 00:12:55,330
taking the calcium ions out of
the inside of the cell so the

223
00:12:55,330 --> 00:12:58,830
muscle is relaxed so that you
can't have your myosin climb

224
00:12:58,830 --> 00:13:00,330
up the actin.

225
00:13:00,330 --> 00:13:03,190
But then when it gets the
signal, it dumps it back in

226
00:13:03,190 --> 00:13:06,040
and then we actually have a
muscle contraction because the

227
00:13:06,040 --> 00:13:11,280
tropomyosin gets moved out of
the way by the troponin., So I

228
00:13:11,280 --> 00:13:12,090
don't know.
That's pretty fascinating.

229
00:13:12,090 --> 00:13:14,160
It's actually even fascinating
that this is still not

230
00:13:14,160 --> 00:13:16,200
completely well understood.

231
00:13:16,200 --> 00:13:19,140
This is an active-- if you want
to become a biological

232
00:13:19,140 --> 00:13:21,360
researcher, this could be an
interesting thing to try to

233
00:13:21,360 --> 00:13:22,330
understand.

234
00:13:22,330 --> 00:13:25,740
One, it's interesting just from
a scientific point of

235
00:13:25,740 --> 00:13:27,900
view of how this actually
functions, but there's

236
00:13:27,900 --> 00:13:31,630
actually-- there's maybe
potential diseases that are

237
00:13:31,630 --> 00:13:34,210
byproducts of malfunctioning
proteins right here.

238
00:13:34,210 --> 00:13:37,050
Maybe you can somehow make these
things perform better or

239
00:13:37,050 --> 00:13:37,770
worse, or who knows.

240
00:13:37,770 --> 00:13:41,960
So there actually are positive
impacts that you could have if

241
00:13:41,960 --> 00:13:44,750
you actually figured out what
exactly is going on here when

242
00:13:44,750 --> 00:13:47,440
the action potential
shows up to open up

243
00:13:47,440 --> 00:13:48,490
this calcium channel.

244
00:13:48,490 --> 00:13:49,770
So now we have the
big picture.

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We know how a motor neuron can
stimulate a contraction of a

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cell by allowing the
sarcoplasmic reticulum to

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allow calcium ions to travel
across this membrane in the

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cytoplasm of the cell.

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And I was doing a little bit of
reading before this video.

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These pumps are very
efficient.

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So once the signal goes away and
this door is closed right

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here, this this sarcoplasmic
reticulum can get back the ion

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concentration in about
30 milliseconds.

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So that's why we're so good at
stopping contractions, why I

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can punch and then pull back my
arm and then have it relax

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all within split-seconds
because we can stop the

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contraction in 30 milliseconds,
which is less

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than 1/30 of a second.

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So anyway, I'll see in the next
video, where we'll study

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the actual anatomy of
a muscle cell in a

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little bit more detail.