Muscle (Marx)

1. We learn about "sliding filaments" to explain the process used by muscles to __________. It is a cycle of _________ events that cause _____ and _____ myofilaments to slide over each other, contracting the _____ and generating _____ in the muscle. 2. To understand this, you must understand the sarcomere. The sarcomere is the structural and contractile unit of a myofibril in *striated* muscle. It is composed of various proteins that are represented as bands in an EM. When considering these bands, the sarcomere is the segment between two, parallel _____ - lines. _____-lines are composed of a mixture of _____ myofilaments and other proteins that maintain the structure of the muscle & keep it from being ripped apart. The _____ myofilaments attach _____ to the ____-line. ______ myofilaments are the only myofilaments to attach to the _____-line; ____ do not. 3. The Z- line runs down the center of the ______- band, which alternates consecutively with the A-band. The ___-band is the region where *myosin* myofilaments do not cross over/onto _____ myofilaments; thus, the ___-band is strictly composed of ______ myofilaments. It shows up as the ______ colored band on EM. It's _____ changes depending on level of contraction. 4. The band sandwiched between two neighboring I-bands is the ____-band; it is in the ____ of the sarcomere. It contains the entire length of a single _____ myofilament. *(Note: the bands go horizontal, not vertical) It shows up as the ______ colored band on EM. 5. There is a region within the center of the A-band known as the ____-band. This represents the "non-binding region" of the myosin filaments. Therefore, ____ myofilaments do not cross over/onto the myosin myofilaments in this space. It shows up as a thin, ______ colored band on EM. It's _____ changes depending on level of contraction. What happens to this band when the muscle is fully contracted? Why? What enzyme is found in this band and what is its function? 6. Within the H-band (which is within the _____-band), is a line known as the _____-line. It is composed of ______ myofilaments and structural proteins that help to maintain the orientation of the muscle (like the Z-line). 7. So how does contraction occur? The _____'s of the myosin myofilaments bind and release from the _____ myofilament (via their ______ - binding site), pulling themselves along the ____ myofilament. 8. Expansion and contraction only occurs within the _____-bands and the _____-bands; the myofilaments themselves do not contract or expand and so the _____-band remains constant. Also, neither of the lines (can) contract or expand. To be clear, this means that the *only bands to actually shrink during contraction are the ____-bands and the _____-bands.* At the level of an individual sarcomere the amount of force and movement generated is small. However, when this is multiplied by the numbers of sarcomeres in a myofibril, myofibrils in a myofiber and myofibers in a muscle, the amount of force and movement generated is significant.

*1:* Contract Repetitive Actin and Myosin Sarcomere Tension *2:* Z-lines Z-lines Actin Actin Directly Z-line Actin Z-line Myosin *3:* I-band I-band Actin I-band Actin Lighter Width *4:* A-band Center Myosin Darker *5:* H-band Actin Light Width It basically disappears bc you're at maximal overlap. Creatine kinase; it helps to form ATP *6:* A-band M-line Myosin *7:* Head's Actin Actin Actin *8:* I-bands and H-bands A-band I-bands and the H-bands

*Read all of card before answering. Skeletal muscle has two different fiber types based upon innervation. Name them and describe them. Be sure to say which is more common. What is the term for a sensory receptor that receives stimuli from within the body, especially one that responds to position and movement? What does that have to do with this topic? What are is the 2nd type of muscle fiber part of? Compare and contrast this type of muscle fiber is innervated by based up contractile vs. non-contractile parts.

*Extrafusal muscle fibers* are the skeletal standard muscle fibers that are innervated by alpha motor neurons and generate tension by contracting, thereby allowing for skeletal movement. This is the majority of skeletal muscle (and what we focused on in this lecture). *Intrafusal muscle fibers* are skeletal muscle fibers that serve as specialized sensory organs (*proprioceptors*) that detect the amount and rate of change in length of a muscle (stretch, shortening and movement). Intrafusal muscle fibers constitute the *neuromuscular spindle.* They are are innervated by *sensory nerve endings* in non-contractile parts and by *gamma motor neurons* in contractile parts.

Lets discuss the sarcomere and the contractile proteins within it: 1. What type of protein is Actin? 2 What is a single actin monomer called? 3. What is a chain of multiple actin monomers called? 4. What does such a chain do to become a "thin filament" of a muscle cell? 5. How many other proteins are thin filaments associated with? Name them.

1. A globular protein 2. G-actin 3. F-actin 4. It wraps around another chain of F-actin so that a double helix is produce. The two chains of F-actin anchor to the *Z-disk* of the sarcomere. 5. Two: tropomyosin and troponin

Comparison of skeletal muscle to *cardiac muscle:* Give 7 differences of cardiac muscle. Be sure to name the specialized cell types. Give 2 similarities.

1. Diads instead of triads: a T-tubule interacts with just one sarcoplasmic reticulum disc 2. More mitochondria within cell 3. Cells joined by *intercalated disks* that transmit signals btwn the cells 4. Cells aren't as long 5. Nuclei are in the center of the cell 6. There is branching (none in skeletal) 7. Have specialized types of cardiac cells for conducting the hearts electrical signal to contract: *Purkinje fibers and Bundle of His* 1. Both are striated 2. Same myofilaments and proteins associated w/ them

1. What is troponin? 2. It is a complex consisting of how may subunits? Name them and give their function. 3. Calcium binds to troponin __ ; what happens when this occurs? What is the end result?

1. It is one of the two proteins associated with actin filaments (the other being tropomyosin) 2. Three: -- *Troponin T* binds troponin to tropopmyosin -- *Troponin C* binds calcium -- *Troponin I* binds actin, which inhibits myosin from binding to actin 3. Calcium binds to Troponin I. This triggers a conformational change in troponin that allows myosin to interact with actin. This is what allows muscle to shorten and generate force.

1. What is tropomyosin? 2. What is it made up of/ look like 3. Where is it located?

1. It is one of the two proteins associated with actin filaments (the other being troponin) 2. It is made up of two long proteins that are coiled around each other 3. It sits in the groove between the two actin strands

Lets discuss the sarcomere and the contractile proteins within it: 1. We know that actin is the primary protein in thin filaments; what is the primary protein in thick filaments? 2. Approximately how many of these proteins are in a single thick filament? 3. Describe the structure of this protein and how it forms a filament. 4. How does it interact with actin? This interaction drives the driving force for movement- what chemical rxtn facilitates this movement? 5. What line does the thick filament bind to?

1. Myosin 2. Approx. 200-300 myosin are in a single thick filament 3. Myosin has a long, alpha-helical coiled-coil tail and a head that *can bind actin and ATP*. The tail enables several molecules to self-assemble into a filament. 4. The head has a site for binding actin. It also has a site for binding ATP, the hydrolysis of which results in a conformational change that generates force and motion. 5. The M line

What are the 3 types of muscle? Differentiate voluntary and striated. What do they do? What contractile proteins do they have?

1. Skeletal (voluntary and striated) 2. Smooth (involuntary) 3. Cardiac All three types shorten (pretty much all it does). All three types have the same contractile proteins: Actin and Myosin

What is a muscle fascicle?

A group of muscle cells (aka a group of muscle fibers)

How is a signal transferred from a nerve to a muscle? What is a synaptic cleft?

A motoneuron ends at a motor end plate on a muscles surface, where the signal is transferred from the nerve to the muscle across a synaptic cleft. A synaptic cleft is an invagination on the surface of the muscle cell coated with basal lamina Acetylcholine (ACh) is released from the motor neuron into the synaptic cleft, where it binds to ACh receptors within the muscle. This binding causes a a depolarization in the sarcolemma (plasma membrane) of the muscle cell, causing it to open up. The nerve signal then becomes an electrical signal.

What is the very first thing that needs to happen in order for a muscle to contract?

A signal in the form of an action potential needs to get from the nervous system (via a motor neuron) to the skeletal muscle itself.

Where does a motor neuron go to on a muscle cell?

A single point on the muscle cell called the motor end plate.

What type of muscle is found in vessels? In the bladder?

Both smooth muscle- don't need generate tremendous force, but do need to contract continuously w/out fatiguing

The sarcoplasmic reticulum stores _______ ions, which play a role in muscle contraction. How are they released? What does the sarcoplasmic reticulum wrap around?

Calcium The sarcolemma (plasma membrane) sends long, thin invaginations called transverse tubules (or *T-tubules*) into the muscle. T-tubules transmit the action potential into the depth of the muscle. T-tubules link to the sarcoplasmic reticulum and thus, the signal to contract is passed from the T-tubule to the sarcoplasmic reticulum, releasing calcium ions into the sarcomere (the repeating chains of myofilaments that are found within each myofibril).

Which type(s) of muscle have a smooth and regular appearance?

Cardiac and skeletal muscle have a smooth and regular appearance; smooth muscle does not

What do intercalated disc's show up as in slides?

Darkish bands between the cardiac cells

Why can muscle be specialized to perform so many different functions?

Differences in histology (structure) and biochemistry

What protein aids in delivering the force that is generated in the sarcomere to the sarcolemma (plasma membrane) and then onto the tendon? How does it function? What is a common disease associated with malfunction in this protein and why?

Dystrophin It forms a complex with other proteins. The complex firmly attaches to the basal lamina and then onto the tendon. Muscular dystrophy - proteins are dysfunctional, so delivering force tears the muscle, resulting in muscular degeneration.

Use the picture to describe the makeup of muscle siting the following: Epimysium Fascicles Perimysium Myofibers Endomysium Basal lamina Sarcolemma (plasma membrane) Myofibrils Myofilaments Sarcomeres Actin (thin) and Myosin (thick) filaments **Where would satellite cells be?

Each individual skeletal muscle is enveloped in epimysium (deep facia) and is composed of bundles of fascicles. Individual fascicles are encased in perimysium and have groups of individual muscle cells within them. The individual muscle cells, also called muscle fibers or myofibers, are surrounded by endomysium. Deep to the endomysium is a basal lamina. Deep to the basal lamina is the plasma membrane, aka the sarcolemma. There are myofibrils within the muscle cell that contain repeating contractile units known as sarcomeres. Sarcomeres are composed of myofilaments- thin ones and thick ones. The thin ones contain actin, while the thick ones contain myosin. Satellite cells are deep to the basal lamina, but are outside of the sarcolemma.

What is the name for the layer of CT that surrounds each individual muscle fiber (cell)?

Endomysium

What is the name for the layer of CT that surrounds the entire muscle? What is it analogous to in gross anatomy? Give a pro and con of it.

Epimysium Deep fascia (Dense CT) It limits the spread of infection, but also limits muscle expansibility if inflamed --> creates swelling/pressure

Name the three layers of connective tissue (CT) that sheath muscle cells What is the purpose of this CT? .

Epimysium, perimysium and endomysium. iThe CT serves as a pathway for vessels and nerves to reach individual muscle cells.

Muscle cell is synonymous with muscle ___?

Fiber aka myofiber

A ______ vs. ______ curve relates muscle in a contracted state to muscle in a relaxed state. Skeletal muscles are innately elastic; they are attached to bones via tendons, which maintain the muscle under a constant level of stretch (referred to as the resting length). If this attachment was removed, for example if the biceps was detached from the scapula or radius, it would shorten in length. Muscles exist in this state to optimize the force produced during contraction, which is modulated by the myofilaments of the sarcomere. The contraction of the sarcomere leads to its shortening, which creates force. If a sarcomere is stretched too far, then there will be _____ _____ of the myofilaments and so the force produced will be _____. Alternatively, if the muscle is over contracted, then the potential for further contraction is _____, which will similarly ______ the amount of force produced. Simply put, the tension generated in skeletal muscle is a function of the magnitude of overlap between actin and myosin myofilaments.

Force vs. length Insufficient overlap; reduced Reduced; reduce

What is the shape of smooth muscle cells? Where are the nuclei? How many are there per cell? Why aren't there striations in smooth muscle? Does smooth muscle have the same myofilaments as skeletal muscle?

Fusiform In the center; one per cell Bc skeletal muscle works in a very small range; ie. the sarcomeres individually don't shorten very much. to the contrary, smooth muscle cells have to be able to generate force over a very broad range; ie. when massively distended and stretched (like in bladder) and when empty. A striated pattern is restrictive- it wouldn't allow force to be generated over such a broad range. Skeletal muscle undergoes extensive tissue damage if stretched and also doesn't generate force if the overlap between the thick and thin filaments is damaged. So, the seemingly random pattern of the thick and thin filament's in smooth muscle permits such a broad range. When stretched out u have the same thick and thin filament proteins as in skeletal muscles, they just aren't grouped together. Thus, they have a broader range and can generate force when the fiber is very long or very short.

Discuss nuclei in a muscle cell. Ie. quantity, nomenclature, location

Individual muscle cells have multiple nuclei (aka multi-nucleated). Muscle cells also contain nuclei from other types of cells such as satellite cells, so to be specific muscle nuclei are referred to as myonuclei. Myonuclei are located at the periphery of the muscle fiber, deep to the sarcolemma (plasma membrane), but superficial to the myofibrils.

Skeletal muscle varies in characteristics based on function: Can be small and highly _____ for fine control, like in the eye Can be large, which is less _____ and has a higher quantity of muscle _____ for large forceful movements, like quad's Some contract rapidly (___ ____) generating large amounts of power Some specialized to contract for hours (___ ____)

Innervated Innervated; fibers Fast twitch (generate more power); slow twitch (generate less power)

What does a motor neuron or "motor unit" consist of? What does a small motor unit result in? Give an example. What does a large motor unit result in?

It consists of a single motor axon (the "parent" nerve cell and all of its branches) and all of the muscle fibers (cells) that it innervates. Small motor units result in fine control. Ex: the eye: each motor nerve goes to a SINGLE muscle fiber Large motor units occur in large, powerful muscles. Each motor nerve SPLITS and goes to MANY muscle fibers

What is the sarcoplasmic reticulum? What does it wrap around and what is its function?

It is a specialized type of smooth endoplasmic reticulum (ER) that wraps, like a sleeve around, the individual myofibrils and stores and releases calcium

What does "myo" refer to?

Muscle

A _________ runs the entire length of a muscle fiber and is broken up into many ________. A single one of these goes from ___ line to ___ line and shortens a pretty insignificant amount, but when you string multiple ones together you end up with the gross change in muscle length that results in ______.

Myofibril Sarcomeres Z line to Z line Movement

Does a motor neuron remain as a single axon when it reaches the motor end plate?

No- a single motor neuron will branch at the motor end plate into a number of smaller axons. Each branch will innervate a single, individual muscle cell.

Is the endomysium the same as the plasma (aka cell) membrane? Explain.

No; the endomysium is a CT layer. The plasma membrane of a muscle cell is called the sarcolemma.

Which bands shrink during muscle contraction?

Only the I-bands and the H-bands

What is the name for the layer of CT that surrounds the fascicles?

Perimysium

What is analogous in smooth muscle to the intercalated discs of cardiac muscle that transmit signals btwn adjacent cells?

Smooth muscle has *gap junctions* that do the same thing

Smooth muscle Describe the appearance of smooth muscle vs. skeletal. Give a few examples of where smooth muscle is found In the GI tract (pic), there are ____ layers of muscle in different orientations to promote _____. Name the layers. What is peristalsis? What is different about how the muscle contracts in skeletal muscle? Smooth muscle is *always* covered by some sort of ______. It's _____ directly exposed to the environment, bc it doesn't handle the environment well at all. Examples of this lining include: _____ lining the blood vessels btwn the blood and the smooth muscle. _____ lining the GI tract. _____ lining the urinary bladder

Smooth muscle is usually in *sheets* vs. bands, like skeletal muscle. Also, smooth muscle is sometimes in bundles (like in the eye). Two; peristalsis Inner circular layer and outer longitudinal layer Peristalsis is a series of wave-like *muscle contractions* that moves food thru the digestive tract. It is a very coordinated movement where one set of cells stimulates the next. This is why gap junctions are necessary - to communicate and coordinate btwn the smooth muscle cells. Skeletal muscle doesn't do that- the entire muscle either contracts or relaxes, so u don't need that kind of coordinated movement along a single muscle fiber. Lining Never' Endothelium Mucosa and absorptive cells Transitional epithelium

What are Purkinje fibers and the Bundle of His? What is their purpose? Do they contract? What effect do they have on the hearts contraction? Can we distinguish purkinje fibers/ bundle of his/ myocytes on our slides?

Specialized cardiomyocytes for rapid delivery of electrical signal throughout heart They don't contract, they just deliver the signal around the heart. The signal stimulates the contraction of the myocardium and is what ultimately allows the heart to contract in a coordinated fashion. No- don't worry about that

How does the electrical signal of a nerve cell get down deep enough into the muscle cells so that all of the contractile proteins can be stimulated at once?

T-tubules and the sarcoplasmic reticulum This pig has a disease of the calcium channels. The uncontrolled release of calcium causes the muscles to contract uncontrollably.

What is a triad? Are t-tubules extracellular or intracellular? What about the sarcoplasmic reticulum?

The junction where a T-tubule (which is "outside" the cell) contacts two lateral SR channels (which are "inside" the cell) is called a triad (triads are indicative of skeletal muscle).

Why wouldn't you be able to see the nuclei in a muscle cell on a histo slide?

The plane of cross section didn't catch them.

Where is the sarcolemma in relation to a myofibrils? What is its roll in muscle contraction? Why do you need the t-tubules to go so far down (deep) into the muscle fiber?

The sarcolemma is the plasma membrane of the cell, so it surrounds the entire muscle fiber, not the individual myofibrils. It is what sends t-tubules down into the muscle. Those t-tubules link to the sarcoplasmic reticulum, transmitting the signal to contract. Once the SR gets the signal, it releases the calcium ions into the sarcomere's of the myofibrils. Calcium binds to Troponin I (a protein found in the thin (actin) filament. This triggers a conformational change in troponin that allows myosin to interact with actin. This is what allows muscle to shorten, contract and generate force. You need the t-tubules to go deep so that you get a nice and uniform release of calcium across all the sarcomeres of all the myofibrils so that the muscle will contract as a unit.

What is the basic contractile unit of striated muscle? What generates muscle contraction?

The sarcomere The linking of myosin to actin generates muscle contraction.

What's different about the thin filaments in smooth muscle compared to skeletal muscle? What about the sarcoplasmic reticulum? What effect does this have?

The thin filaments don't have troponin or the banding pattern found in the sarcomere. Also, smooth muscle cells have very little sarcoplasmic reticulum. As a result, most of the calcium comes from outside of the cell, which is ok bc the fibers are way smaller than skeletal so its easier for that calcium to diffuse rapidly into the cell (opposed 2 skeletal which would take forever)

What do satellite cells do? Why are they needed? Are they easy to differentiate from muscle cells under light microscopy? How would you do so with a better view?

They are involved repair and *regeneration* of damaged muscle; get activated when there is injury to muscle They are necessary bc mature muscle cells are *post-mitotic*, but satellite cells can *create new muscle nuclei* and cells in the event of injury. No, they are not. You won't be asked to do this. Myonuclei lie deep to the sarcolemma, while satellite cells lie superficial to it (but still within the basal lamina).

The Z-line and M-line proteins both function to maintain the structure and orientation of the muscle w/in the sarcomere. There are ____ additional proteins that also aid in this purpose. Name them and give their location and function.

Three: *Titin* extends from the Z-line to the M-line. Helps to maintain the myosin filaments. *Nebulin* runs parallel/ together with actin from Z-line to Z-line. Helps to maintain the actin filaments. *Desmin* extends from the sarcolemma down thru the muscle fiber, between the myofibrils. It helps to maintain the conformation of the muscle fiber during contraction.

What type of tissue is this? How do you know? Where can you see the striations? Note difference btwn single muscle cell and single muscle fascicle in cross section on pic**

Tongue; bc muscle fibers go in many different directions so tongue can move all around (usually muscle fibers go in one direction). Striations can be seen in longitudinal section. Top left: endomysium Top right: perimysium

The troponin-tropomyosin-actin complex: *Tropomyosin* consists of _____ nearly identical alpha-helical polypeptides twisted around each other. Tropomyosin runs in the _____ formed by ___-actin strands. Each molecule of tropomyosin extends for the length of ______ actin monomers and binds the _______ complex. *Troponin* is a complex of 3 proteins: Troponin ___ binds the complex to tropomyosin. Troponin ____ inhibits the binding of myosin to actin. Troponin ____ binds calcium and is only found in striated muscle.

Two Groove F Seven Troponin T I C

What are Dihydropyridine receptor and Ryanodine receptor? What do they do?

Two protein receptors that get stimulated when an electrical signal is passed down thru the t-tubles to the sarcoplasmic reticulum. When they are stimulated, they open up and allow calcium to flood out of the sarcoplasmic reticulum, into the cell. Therefore, they link the depolarization of the SR to calcium release. Ultimately, this is what stimulates muscle contraction.

How does calcium get back into the cells so that a contracted muscle can relax again?

Via a protein in the sarcoplasmic reticulum called an ATPase Pump

Which bands can you see when you look at skeletal muscle thru a light microscope?

You see the A bands - that's what gives muscle its striated appearance. They are very regular and repeat the length of the muscle. You can not see the I band, the H band or the Z or M lines, but you can recognize the thick and thin filament banding pattern in general.

What is a motor neuron (aka nerve)?

a nerve cell that forms part of a pathway along which impulses pass from the brain/spinal cord to a muscle (or gland)