13-THE MUSCULOSKELETAL SYSTEM KHAN ACADEMY NOTES

Autonomic nervous system can be further divided into:

1. Sympathetic NS→Fight or Fly 2. Parasympathetic NS→Rest and Digest Both of these branches are responsible for non voluntary movements.

So for the muscle contraction to take place we want as many myosin heads working as possible. How can we increase the amount of myosin heads that help move actin?

1. ↑ Increase Ca²⁺ concentration in cell even higher 2. Troponin C can become more "sensitive" to the calcium that is already around in cell so that you don't need that high of concentrations of Calcium. So it binds Calcium more easily.

So what happens when muscle needs to contract?

Calcium ions from the sarcoplasmic reticulum will be dumped inside the cell. These calcium will bing to troponin and its configuration will change effecting tropomyosin and exposing acting binding sites for myosin head.

What will make the tropomyosin to move out of the way so that myosin can bind to actin?

Calcium. Calcium binds to Troponin complex C and that binding it will change configuration of troponin and tropomyosin will be moved out of the way of binding site of actin and myosin can bind.

How does the message gets passed from the brain to muscle?

In the brain we have UPPER MOTOR NEURON that sends signal to LOWER MOTOR NEURON that will directly synapse on the muscle to tell it to start contracting.

Lets investigate on how nervous system is directing movement and controls the calcium levels in the muscle cell?

In this case neuron will synapse on muscle cell directly (not on dendrites of another neuron). Muscle cells have small indentation (or when you look from the top there is a small hole) called T-Tubule. Inside the muscle cell there is SARCOPLASMIC RETICULUM that is full of Calcium ions.

Moving on to Voluntary and Involuntary muscle movements:

Involuntary: -cardiac -smooth muscles Voluntary: -skeletal muscles

So what does Somatic NS do?

It controls the voluntary movements. The neurotransmitter that we use in here is Acetylcholine.

What happens to I bend as sarcomere contracts?

It gets smaller. Z-disks get closer together. Notice that A band does not changes during contraction.

What does the Sarcoplasmic reticulum does?

It stores lots of Calcium inside. It has Calcium ion pumps on its membrane. They use ATP to pump Calcium inside the reticulum against the gradient. These ate ATPase pumps. So when muscle is at least you have lost of Calcium in sarcoplasmic reticulum.

What is SARCOMERE?

Its a basic unit of contraction. This is where actin and myosin fibers interact to produce movement.

So what part moves? Does actin moves or does myosin moves in here.

Its actually actin that will be moving closer to the center and myosin will be pulling on it.

What is tendons made of?

Its connective tissue that is continuation of the connective tissue that covers muscle. Its main job is to attach muscle to the bone.

How is smooth muscle controlled?

Its involuntary control-automatic

How is cardiac muscle controlled?

Its involuntary-its automatic

How is skeletal muscle controlled?

Its voluntary controlled so we make decision if we want to move our arm or not.

What does the Lower motor neuron do?

LMN directly synapse onto muscle and secretes Acetylcholine onto muscles. It has one job: tell the muscle to start contracting

Lets now move on to the anatomy of the muscle:

Lets first take a look at the cross section of a muscle. Lets say a biceps muscle. What do we see? Look at the next slid there is a better picture.

So lets now focus on the muscle cell.

Lets look at the shape of the muscle cell. Its long like a tube but it has many bumps on it. Do you know why there are bumps? There are nuclei that sits on the outside on the muscle cells. Towards the edge of plasma membrane. Nucleus is a storage unit of DNA of the cell.

What is the function of tropomyosin?

Lets redraw our actin filament and on top of actin you have protein called tropomyosin that coils around actin. Tropomyosin is attached to actin by another protein called: TROPONIN. Troponin directs the spots in which tropomyosin will be attached.

But when we say muscle the main thing I want you to think about is:

MOVEMENT All different types of movement: leg movement, heart beating, food moving through your GI track...

Great we learned so far about the anatomy of the muscle cell. Lets now move on and learn about how our nervous system can control skeletal muscles through what is called MOTOR UNIT:

Motor neurons are nerve cells that come from our brain and innervate muscles to direct movement.

What is the name of the plasma membrane is muscle cell?

Sarcolema

So when muscle contracts we are:

Shortening the length of the sarcomere

What is so important about Endomysium?

Since it surrounds each muscle fiber/muscle cell it has all the blood vessels that delivers oxygen and nutrients as well as it has many motor nerve endings that will control the muscle moment.

why muscle cells have multiple nuclei?

Skeletal muscle fibers are made when myoblasts fuse together; muscle fibers therefore have multiple nuclei (each nucleus originating from a single myoblast). The fusion of myoblasts is specific to skeletal muscle (e.g., biceps brachii) and not cardiac muscle or smooth muscle.

Lets move on now to Neuromuscular Junctions: this is the places where motor neurons directly talk to muscle and let them know to start contracting.

The Axon terminal of the lower motor unit will sit very close to the muscle that it will control it. The muscle will have infolding called T-Tubule that will increase the surface area and allow more Na⁺ channels to be present on the cell membrane. There is a space between the neuron terminal and muscle called: NEUROMUSCULAR JUNCTION

Lets now learn about two types of muscle fibers: Type 1 and Type 2.

The Golden rule that we need to keep in mind in here is that: MITOCHONDRIA IS PRESENT IN HIGHER QUANTITY IN TYPE 1 MUSCLE FIBERS. Based on that we will be filling out a table.

What happens when Ach is located in the synaptic cleft?

The Na⁺ channels have NICOTINIC ACETYLCOLINE receptors on them that will bind Acetylcholine and when that happens they will open. Na⁺ will flow inside the muscle cell and depolarize the cell.

So what happens when muscle is not contracting?

Tropomyosin is blocking myosin head from attaching to actin. So there is no movement. Or if myosin is being attached to actin tropomyosin will preventing it from sliding along actin. It physically blocking the binding site of myosin head to actin.

So how can we unblock the tropomyosin so that myosin head can attach to actin?

Tropomyosin must change configuration and the binding site will be exposed so that myosin head can attach.

Which type of the muscle type 1 or 2 are more likely to fatigue faster?

Type 1 can contract for long times so they will be fatigue resistant. Type 2 are easily fatigue.

Lets start with color?

Type 1 muscle fibers are red. Why is that? Mitochondria are used in the oxidative phosphorylation to make ATP which is energy. To make TAP we need oxygen that is carried in RBC which are red. Type 2 muscle will be white.

How about the power of contraction? Type 1 vs Type 2muscle fibers?

Type 1 muscle fibers generate less immediate force but they last long time. Type 2 muscle fibers generate stronger immediate force but they get tired very easily.

How do we store energy in type 1 vs type 2 muscle fibers:

Type 1 muscle fibers have lots of mitochondria that produce lost of energy in form of ATP. So that ATP will be stored in the form of triglyceride which is fat for later use. Type 2 muscle fibers will use raw ATP and Creatine Phosphate

Next lets compare in Speed of Contraction in Type 1 muscle fibers and Type 2 muscle fibers:

Type 1 muscle fibers will have SLOW contraction speed. The reason for that is that it takes time for mitochondria to produce energy. We must go through glycolysis and Krebs Cycle to make ATP and that takes time. Type 2 muscle fibers will have fast contraction speed.

What type of activity will Type 1 muscle fibers perform vs. Type 2 muscle fibers?

Type 1 muscle fibers will have aerobic respiration-they have more mitochondria so they will need oxygen. Type 2 muscle fibers will have anaerobic respiration. No oxygen will be needed.

What is the neurotransmitter for ParaSympathetic NS?

-Acetylcholine

So lets now identify the bands on sarcomere:

-First band is A BAND and it includes Myosin and Actin -Second part is I BAND is only actin (no myosin is included in here)

What parts of our nervous system we use for voluntary control?

-In brain we have cerebral cortex and that voluntarily controls skeletal muscles. -Spinal cord will also contribue to voluntary control of muscles Note that both Cord and Cortex start with C-control :)

What is the neurotransmitter for Sympathetic NS?

-Pre ganglionic is Acetylcholine -Post Ganglionic is Norepinephrine (adrenaline)

Lets now compare how the cells of the 3 muscles look like if you look at them with microscope:

-Smooth muscles cell looks like "eye" with one nucleus in the middle -Cardiac muscle cell is branched (not all of them but most) they have nuclei sometimes one and sometimes two. -Skeletal muscles cell is long tubular shape and has "bumps" on the edge that are nuclei-so they have many nuclei on the edges.

Anatomy of muscle:

-Tendon connects muscle to bone -Epimysium is a continuation of tendon and it serves to protect the muscle and it surrounds it -Perimysium the sheath of connective tissue surrounding a bundle of muscle fibers -As you can see muscle fibers are organized into bundles called FASCICLE -Each Fascicle has many MUSCE FIBERS that are covered with another type of connective tissue called ENDOMYSIUM -Muscle fiber or Myofiber is a muscle cell

What parts of the nervous system we use for involuntary control of our muscles?

-The brain stream is responsible for directing blood flow to different organs depending on body's needs, it also vascodilates and vascocontract veins in our body. -Sympathetic Ganglia is also responsible for controlling non voluntary muscle contractions

How about speed of the 3 types of muscles?

-The smooth muscle is the slowest (so vasoconstriction and moving food through GI track is slow process) -The cardiac muscle is in the middle -The skeletal muscle is the fastest (If you want to jump that happens very quickly)

So the big picture to remember in here is:

-action potential travels down -Acetylcholine is secreted into synapse -Acetylcholine binds to receptors on the muscle cell and opens Na channels -Depolarization travels down to T-Tubule in the muscle cell -Calcium is secreted from the sarcoplasmic reticulum -Calcium binds to troponin and its configuration will change effecting tropomyosin and exposing acting binding sites for myosin head. -Movement will occur. Once the signal goes away the Calcium pumps in the sarcoplasmic reticulum will pump all the Calcium back inside in 30 millisecond!!! Super fast.

As we can see the axon of the lower motor neuron is very long. As result there can be some problems associated with that. What problems can happen?

-signal can die off and it would never get to muscle. This is what happens when you have lower neuron damage. Usually the damage must be severe since the signal will not just disappears since the axon is isolated with myelin sheets. -If you have upper neuron dame you also can develop weakness since the signal will never get into the lower motor neuron at the first place. But if somebody has upper motor neuron injury the very characteristic feature is that you can't stop the movement. This will happen since the upper motor neuron is not working and unable to stop the lower motor neuron from signaling the muscle to contract. So the key symptom in damage to upper motor neuron is Spasticity.

What did we learned so far about smooth muscles:

-smooth muscles are responsible for involuntary movement such as moving food through the digestive tack→PERISTALSIS -smooth muscle also helps us regulate blood pressure by vasodilation and vascocontraction

So far we learned about skeletal muscle:

-they support the body and look for body movement -the contraction of skeletal muscle compresses veins and move blood through low pressure venous system toward the heard but also the lymph through lymph system -rapid skeletal muscle contractions are called shivering and are meant to raise body temperature

What did we learned about the cardiac muscles:

-this is special kind of muscle that also can maintain a rhythmic contractions of the heart without the nervous input

How will influx of Na⁺ and depolarization of muscle cell make it contract?

AT that point the membrane will be depolarized so much that voltage gated Calcium channels that are located on the muscle cell membrane will open. So calcium from outside of the cell will start entering the cell and depolarizing membrane even more. In addition we have sarcoplasmic reticulum inside the muscle cell that is full of Calcium and that calcium will be released when membrane will become very depolarized. This is called Calcium induced Calcium released.

What is Actin?

Actin is rope like looking protein.

Lets see now how lower motor neuron secreters neurotransmitters?

Action potential will be travel down the axon depolarizing membrane opening Na⁺ channels. When it gets to the axon terminal it will open voltage gated Ca²⁺ channels that will let Ca²⁺ inside the neuron. This influx of calcium will trigger release of neurotransmitter Acetylcholine from the presynaptic terminal into the synaptic cleft.

So when you think of skeletal muscle contracting thing that:

All of the muscle cells are connected by gap junctions that will allow the depolarization to spread from cell to cell so that the muscle contracts as one unit. We say that our muscles are in syncytium. So if one muscle cell start contracting it causes the neighbor to contract as well.

Nervous system can be split up into: Autonomic Nervous System and Somatic Nervous System.

Automatic controls the involuntary muscle contractions. Somatic nervous System is a system that we can control so its responsible for voluntary muscle contractions and movements.

So what happens next, after our brain senses that its hot outside?

Brain will sent back signal to our body to respond to hot temperature. Its our muscles that will perform some task to make sure that we maintain our body core temperature.

So what makes myosin move or stop moving along actin?

Changes in calcium concentrations. -High Calcium concentration exposes actin binding sites and allows myosin head to bind and movement happens -Low Calcium concentration keeps tropomyosin in place and that blocks the bonding sites for myosin head to clime up actin. No movement happens.

Muscles can be divided into 3 types: skeletal, smooth and cardiac.

Each of the muscle performs special function however all muscles are able to contract which is dependent of Ca²⁺ and all muscles are innervated by nervous system but some more then others.

Where can we find cardiac muscle?

Heart only

What makes tropomyosin change configuration?

High Calcium concentrations. Ca²⁺ will bind to troponin and that will change configuration of troponin and as result this will move tropomyosin out of the way and expose actin binding sites.

So think in here about the movement of actin in comparison to myosin?

If actin is stationary and myosin is pulling on it then actin will be stationary and myosin will be moving to the right in here. Try drawing the direction of movement.

So how will the muscles respond to hot temperatures?

In hot temperature only smooth muscle will respond by vasodilation and allowing more blood to get to surface of the skin and heat will be lost that way. In cold temperate smooth muscles in arterioles would vasoconstruct and less blood will be reaching the skin and less heat would be lost.

We have some prefixes in here that are worth knowing:

Myo- means muscle. Sacro- means Flesh So you have: Sarcolema-plasma membrane Sarcoplasm-cell plasma Sarcomere-basic unit of muscle

To understand the movement we need to look at the molecular levels and focus on 2 proteins: MYOSIN AND ACTIN.

Myosin and actin interact with each other, using energy harvested from ATP they can produce movement. This mechanical movement is directed by Nervous system.

How does myosin and actin will interact?

Myosin essentially uses ATP to crawl along actin and that is what creates mechanical movement.

One of the questions when myosin is pulling on the actin if in step # 2 when myosin detached from actin would actin just move back to original position? There is a lot of tension in actin.

No because this is not the only myosin that is acting on this actin so if one myosin detaches 100 different ones are still attached to actin and holding it in place. So there are many many myosin heads that are holding and detaching but in different times so actin will not move back into original position.

So each muscle fiber/muscle cell is made out of smaller units: they are responsible or contraction of muscles.

One of the subunits of muscle cell is called MYOFIBRIL

Which of the 3 muscle cell types are STRIATED? (when you look under microscope you can see stripes)

Only cardiac and skeletal not smooth.

How will the muscles respond to cold temperatures?

Skeletal muscles would shiver. This will take ATP but some heat will be produced.

What type of muscle will be involved in thermoregulation?

Smooth muscles and skeletal muscles.

Now lets zoom in at the myosin and actin interaction: In here actin is in pink and myosin is in purple.

So actin will have binding sites that myosin can bind to. Normally when the muscle is relaxed these sites will be covered with another protein called tropomyosin. There is also another protein is called Troponin complex (3 part to that protein C, I and T-in blue in here).

What does the Upper Motor Neuron do?

So it will sent the action potential to lower motor neuron to start muscle contraction but it also has a second job that is the it will tell the lower motor neuron to stop contracting muscles. So upper motor neuron has 2 jobs: telling lower motor neuron to start and to stop contraction of muscles.

The last topic to cover in here is Thermoregulation that is performed by muscles?

So lets look at this situation. One day you go outside and you put your hand out and you sense that is very warm. That signal will travel from your hand to brain area called Hypothalamus. Hypothalamus is actually split into two different parts to respond to two different temperatures. Anterior Hypothalamus will respond to the Hot temperature. Posterior Hypothalamus will respond to the cold temperature.

Where can we find SKELETAL MUSCLES:

So one of the things about skeletal muscles is that they are attached by TENDONS to bones in the skeleton and they can move the body that way. So does every skeletal muscle is attached to bone? No, muscles of external oblige muscles (located in stomach) are not attached to tendons and bones. So not all the skeletal muscles are attached to bone.

So when we are talking about Calcium concentrations we are talking about calcium concentration in muscle cells. They might be high and that will produce movement or they might be low and there will be no movement.

So the next question that we need to ask ourselves is how muscle cells regulate whether we have high or low Calcium concentration inside the cell? The big answer is that nervous system is doing it.

But how does the sarcoplasmic reticulum knows when to dump Calcium inside the cell?

The motor neuron is signaling for muscle contraction. Depolarization travels down toward the axon terminal, at the very end voltage gated Calcium channels open and calcium gets inside the neuron this triggers release of neurotransmitter from the synapse. As result Acetylcholine is secreted into synapse. Acetylcholine binds to the receptors on the muscle cell and that opens Na⁺ channels on muscles cells. Na⁺ rushes inside the cells and depolarization which is action potential in muscle cell takes place. The opening of the Na⁺ channels in the T-Tubular is very important in here since there is a special protein complex that connects T-tubule and sarcoplasmic reticulum that allows Na⁺ enter sarcoplasmic reticulum and that will trigger the secretion of the calcium from the sarcoplasmic reticulum. So all the Calcium will be dumped inside the cell.

So now that we understand the structure of sarcomere lets see how it works?

The motor neuron will sent action potential and as result Acetylcholine will be secreted into synaptic space. Acetylcholine will bing to receptors on sarcolema and open Na channels that will spread the depolarization inside the cell. Sarcoplasmic reticulum will then secrete Ca²⁺ that will bind Troponin that sits on actin will change configuration and as result tropomyosin will expose binding sites on actin for myosin. Myosin will use ATP to walk along actin and contract muscles.

So we just discussed how we make one muscle cell contract but of we want to move arm we need many muscle cells contacting at the same time. How we do this?

The muscle cell that just become depolarized is attached to another muscle cell by proteins called GAP JUNCTIONS. So the depolarization wave will spread from cell to cell through Gap Junctions. Since the ions like Calcium and Sodium will flow through gap junctions and cause depolarization of the membrane in the nearby cell.

The muscular system:

The muscular system is composed of 3 types of muscles. Skeletal, cardiac and smooth.

Lets now zoom in on sarcomere:

The outsize you have Z lines (in yellow) to the Z lines you will have actin filaments that are attached (in purple). Insider you will have myosin filaments that has 2 heads and its associated with actin and wants to crawl along actin. Notice the attachment of myosin to actin. Myosin is also attached to Z lines by TITIN (white)

How does our body turns on and off this system of myosin crawling up actin?

To understand that you need to know two more proteins: -TROPOMYOSIN -TROPONIN

What is MYOSIN?

Their protein is protein-enzyme called ATPase since it takes ATP and cleaves it into ADP+P Notice the shape of myosin-it has ball like structure at the end called myosin head.

So lets move on to the next subject which is different types of muscle fibers:

There are two types of muscle fibers. Type 1 and Type 2.

What we see when we look at myosin binding to ATP and hydrolyzing ATP?

This is where chemical energy is being transformed into mechanical energy-Power stroke and a movement of the muscles will take place.

What is the duration/how long will the type 1 muscle fibers contract in comparison to type 2?

Type 1 muscle fibers will have long duration of contraction. Think about that. We are making lost of energy with mitochondria so we can do more work. Type 2 muscle fibers will have short duration of contraction. What are the implements? Muscle in my back that we use for standing or legs are the ones that can contract for a long time. So we can stand for a long time or walk. Muscle in my arms, fingers contract for short time only. So we can use them for w while and then they get tired.

How about CONDUCTION velocity, which is the speed at which we will be able to receive neuronal input to Type 1 and 2 muscle fibers to contract.

Type 1 muscle fibers will have slow conduction velocity. This is called "SLOW TWICH" Type 2 muscle fibers will have fast twitch.

Lets look at the lower motor neuron in better details now:

Upper motor neuron will synapse on multiple dendrites of the lower motor unit. Dendrites of the lower motor unit will receive the information that is coming from the upper motor unit. The information will pass though soma (cell body of the neuron) and then goes on to axon. Notice how long the axon is. Its very long. It eventually it will synapse on muscle.

Myosin and actin interaction that creates movement:

We are starting this process with myosin being attached to actin. Myosin will be moving to the right in here. 1. Myosin head will first bind ATP 2. As soon as the ATP binds to Myosin the myosin head will detach from actin 3. ATP is being hydrolyzed (remember this is ATPase enzyme) so ATP→ADP+P 4. This process releases energy and changes confirmation of myosin so that it can attach to a new space on actin. 5. Phosphate gets detached from myosin this causes myosin protein to push on actin this is called POWER STROKE (yellow arrow). 6. ADP is released and we are back to the bering where new ATP will be binding and new movement will take place.

Where can we find smooth muscles?

When you think of smooth muscle think of hollow organs and blood vessels (aorta, veins)

Lets look at the myofibril under the microscope:

You can see that they have stripes/bends on them. -The Z lines mark one sarcomere -A band is in the middle -I band