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In the last video, we learned how myosin-- and myosin II in

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particular-- when we say myosin II it actually has two

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of these myosin heads and their tails are inter-wound

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with each other-- how myosin II can use ATP to

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essentially-- you can almost imagine either pulling an

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actin filament or walking up an actin filament.

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It starts attached.

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ATP comes and bonds onto it.

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That causes it to be released.

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Then the ATP hydrolyzes into ADP and a phosphate group.

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And when that happens, that energy's released.

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It puts this into a higher energy state.

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It kind of spring-loads the protein and then it attaches

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up another notch on the actual actin filament and then the

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phosphate group leaves and that's where the confirmation

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change in this protein is enough.

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It generates the power stroke to actually push on the actin

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filament-- and you could imagine, either move the

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myosin-- whatever the myosin is connected to-- to the left

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or whatever the actin is connected to to the right.

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We're going to talk a lot more about what they're connected

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to in future videos.

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Now, a couple of questions might have been

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raising in your head.

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This guy had so much effort to pull on this thing, right?

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There's some tension pulling in the other direction, right?

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I said this is what happens in muscles, so there must be some

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weight or some other resistance.

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So what happens when this releases?

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At the first step when ATP joined and this released,

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wouldn't the actin filament just go back to

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where it was before?

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Especially if there's some tension on it

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going in that direction.

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And the simple answer to that is, this isn't the only myosin

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protein that's acting on this actin.

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You have others all along the chain.

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Maybe you have one right there.

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Maybe you have one right there.

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They're all working at their own pace at different times.

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So you have so many of these that when one of them is

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disengaged, another one of them might be in their power

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stroke or another one might be engaged.

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So it's not like you have this notion of, if all of a sudden

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one lets go, that the actin filament will recoil back to

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where it was.

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Now the next question that you might be thinking is, how do I

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turn on and off this situation?

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We have command over our muscles.

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What can turn on or off this system of the myosin

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essentially crawling up the actin?

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And to understand that, there's two other proteins

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that come into effect.

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That's tropomyosin and troponin.

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And so I'm going to redraw the actin-- I'll do a very rough

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drawing of the actin filament.

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Let's say that that's my actin filament right there with its

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little grooves.

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It's actually a helical structure.

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And actually, these grooves-- it's kind of a helical-- but

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we won't worry too much about that.

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What we drew so far, at least in the last video, you had

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these little myosin.

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You can view them as feet or head or whatever that keep

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attaching to it and then based on where they are in that ATP

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cycle, they can keep getting cranked back up or

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sprinr-loaded and go to the next one and push back.

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Now, on top of this actin, you actually have

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this tropomyosin protein.

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And this tropomyosin protein, it coils around the actin.

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So this is our actin right here.

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This is one of the two heads of the myosin II.

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And then we have our tropomyosin.

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Tropomyosin is coiled around.

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It's a very rough sketch, but you can imagine it's coiled

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around and it goes back behind it, then it goes like that,

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and then it goes back behind it, then it goes like that.

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So it's coiled around it and the important thing about it

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is, if there's-- let me take a step back.

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It's coiled around and it's attached to the actin by

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another protein called troponin.

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Let's say it's attached there and-- this isn't exact, but

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let's say it's attached there, and there, and there, and

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there, and there by the troponin.

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So let me write this down.

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So you can imagine, the troponin is kind of like the

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nails into the actin.

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So it dictates where the tropomyosin is.

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So when a muscle is not contracting, it turns out that

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the tropomyosin is blocking the myosin from being able

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to-- and I've read a bunch of accounts on this and I think

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this is still an area of research.

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It's not 100% clear one way or the other.

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Tropomyosin is-- or maybe both-- blocking the myosin

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from being able to attach to the actin where it normally

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attaches so it won't be able to crawl up the actin-- or

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sometimes the myosin is attached to the actin, but it

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keeps it from releasing and sliding up the actin to keep

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that walking procedure.

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So the bottom line is that this tropomyosin kind of

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blocks the myosin head-- this is the myosin head right

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there-- from crawling up the actin, either by physically

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blocking its actual binding site or if it's already bound,

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keeping it from being able to keep sliding up the actin.

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Either way, it's blocking it and the only way to make it

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unblocked is for the troponins to actually change their

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confirmation, for them to change their shape.

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And the only way for them to change their shape is if we

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have a high calcium ion concentration.

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So if you have a bunch of calcium ions, if you have a

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high enough concentration, these calcium ions are going

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to bond to the troponin and then that changes the

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confirmation of the troponin enough to move the

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configuration of the tropomyosin.

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So let me write this down.

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So normally, tropomyosin blocks, but then when you have

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a high calcium ion concentration, they bind to

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troponin and then the troponin, they change their

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confirmation so it moves the tropomyosin out of the way.

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So when it moves out of the way, you have a high calcium

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concentration, bonds troponin, moves tropomyosin out of the

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way, then all of a sudden what we talked about in the last

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video-- these guys can start walking up the actin or

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pushing the actin to the right, however you

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want to view it.

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But then if the calcium concentration goes low, then

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the calciums get released from the troponin.

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You need to have enough to always hang around here.

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If the concentration becomes really low here, these guys

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will start to leave. So then the troponin goes back to, I

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guess, standard confirmation.

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That makes the tropomyosin block the myosin again.

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So it's actually-- I mean, I can't say

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anything here is simple.

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This was only discovered maybe 50 or 60 years ago and you can

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imagine to actually observe these things or to create

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experiments to definitively know what's happening--

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nothing is simple, but the idea is simple.

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Without calcium, the tropomyosin is blocking the

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ability of the myosin to attach where it needs to

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attach or slide up the actin so it can keep pushing on it.

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But if the calcium concentration is high enough,

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they will bond to the troponin-- which essentially

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nails down the tropomyosin that's wound around the actin

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and when they change their confirmation with the calcium

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ions, it moves the tropomyosin out of the way so that the

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myosin can do what it does.

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So you can imagine already, we're building up a way for--

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one, for muscles to contract, but even better, for us to

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control muscles to contract.

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So if we have a high calcium concentration within the cell,

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the muscle will contract.

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If we have a low calcium concentration again, then all

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of a sudden, these will release.

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They'll be blocked, and then the muscle will relax again.

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