Human Phys: Chpt 8 Review

it would decrease acetylcholine release from the motor neuron

A drug that blocks voltage-gated Ca++ channels at the neuromuscular junction would result in muscle weakness because

it would prevent the action potential from causing a large increase in Ca+2 in the sarcoplasm

A drug that prevents a change in conformation of the DHP receptor from its resting state in skeletal muscle would cause paralysis because

Myosin = thick; ~15 nm; ~1500/myofibril Actin = thin; ~5 nm; ~3000/myofibril

Actin and myosin are both contractile proteins and myofilaments. Which one is considered a thick filament and which one is considered a thin filament?

Ca+2 is then put back into the SR by Ca+2-ATPase (i.e., a Ca+2 pump). Note, this is a third role of ATP in contraction. It is important to remember that this process takes a while (~100 msec), whereas the action potential lasts only about 2 msec. These Ca+2 dynamics are important; how quickly the levels in the sarcoplasm go up, and then how quickly they go down.

After Ca is released from the sarcoplasmic reticulum, how is it put back?

They are under the control of the autonomic nervous system, and some also respond to endocrine and paracrine signals. [Remember that we discussed autonomic and endocrine integration at both CNS and peripheral levels (ganglia, target tissues).] In addition, some involuntary muscles can contract in the absence of any signal from outside the muscle (i.e., they are capable of spontaneous contraction; we will discuss some such cells in the gastrointestinal tract).

Both cardiac and smooth muscle aren't under voluntary control. What system are they under the control of?

repeated sequential interactions between myosin and actin filaments at cross-bridges that cause a muscle fiber to contract

Cross bridge cycle

Each muscle fiber is innervated by only one motor neuron, but a single motor neuron may innervate many muscle fibers. The motor neuron and all of the muscle fibers it innervates is called the motor unit. Some motor units are small, consisting of a motor neuron and a few muscle fibers, but others are large, consisting of several hundred muscle fibers. (Which muscle would you expect to have larger motor units: a finger muscle or a thigh muscle?)

Describe how muscle fibers and motor neurons innervate one another. As a collective, what are these called?

In this state (no ATP bound to the myosin head, although ADP and P are still there), the actin and the myosin again bind to each other. The P then dissociates from the myosin, resulting in the change in position of the myosin head to its low energy state (i.e., the power stroke, step 4 in the figure above). The myosin head swings over and binds weakly to a new actin molecule. The crossbridge is now at 90 degrees relative to the filaments.

Describe the 4th step of the cross bridge cycle

This the movement of the myosin head occurs while myosin is bound to actin, the actin is moved along the myosin molecule toward the M line Release of phosphate initiates the power stroke. The myosin head rotates on its hinge, pushing the actin filaments past it

Describe the 5th step of the cross bridge cycle

The ADP then dissociates from the myosin, and the cross bridge cycle can then start again. (one cross bridge cycle shortens a sarcomere by ~ 5-10 nm and takes about 200 microsec; if each thick filament has ~200-300 myosin molecules, then the thick filament can move relative to the thin by ~15 micrometers/sec) - i.e., it can shorten very quickly!) At the end of the power stroke, the myosin head releases ADP and resume the tightly bound rigor state

Describe the 6th step of the cross bridge cycle

In the absence of ATP, myosin heads bind tightly to actin. (This is referred to as the rigor state. Think about the muscle rigidity that occurs following death, rigor mortis. This is the state represented by step 1 of figure 8.8, where actin and myosin are tightly bound to each other.) Tight binding in the rigor state. The cross bridge is at a 45 degree angle relative to the filaments

Describe the first step of the cross bridge cycle

Tail regions of myosin molecules will associate with each other, forming a bunch of tail regions extending in either direction from the M line. (You might picture a myosin molecule like a golf club, with the handles of many of these golf clubs stuck together at the M line.) The head region of myosin can bind to actin (think about each head region interacting with a G-actin). This interaction between the head of myosin and actin is referred to as a cross-bridge.

Describe the interactions between the head of myosin and actin. what process are these interactions crucial for?

Myosin in skeletal muscle is an ATPase (i.e., an enzyme that binds and cleaves ATP). Myosin will bind ATP, and in this state myosin and actin do not bind. ATP binds to its binding site on the myosin. Myosin then dissociates from actin

Describe the second step of the cross bridge cycle

The mysosin cleaves ATP, and the energy liberated from the ATP drives a conformational change in the hinge region of myosin, moving the head to the "cocked position". The ATPase activity of mysoin hydrolyzes the ATP. ADP and Phosphate remina bound to myosin.

Describe the third step of the cross bridge cycle

Sarcomeres shorten in length during contraction because the Z lines get pulled toward each other via the cross bridge cycle. This causes both the H zone and the I band to shorten; however the A band stays a constant length.

During contraction, the sarcomere changes in length. What causes the sarcomere shortening? What bands/zones of the sarcomere shorten and which stay constant?

- contractile proteins and elastic proteins (myosin and actin)

Each muscle is made up of myofibrils, which are bundles of what type of proteins?

When a single AP causes as single unit of contraction

How does a twitch contraction occur?

the portion of the A band that is not the H zone

In the figure above what part of the banding pattern would this be from?

Muscles fibers are bundled together in fascicles and fascicles are bundled together in muscle.

Muscle is made up of a bunch of muscle fibers held in a bundle by connective tissue. What are bundles of muscle fibers called? What do these bundled together form?

MG is associated with muscle weakness because the signal from the motor neuron to the muscle causing contraction is disrupted

Myesthenia Gravis (MG) is a neuromuscular disease in which the immune system destroys nicotinic receptors at the neuromuscular junction. Thus,

Regulating proteins: troponin and tropomyosin Accessory proteins: titin and nebullin

Myosin and actin are the main contractile proteins within myofibrils. What proteins are responsible for regulating contractions? What are the accessory proteins?

half

Nearly what percentage of our body mass is muscle?

1. Helps stabilize position of thick filaments in relation to thin filaments 2. Greatly augments muscle's elasticity by acting like a spring

Titin function

in the absence of ATP, actin and myosin stay tightly bound

Shortly after death, muscles become rigid, a state called rigor mortis. This state of muscles being rigid is caused by

the sarcoplasmic reticulum

Skeletal muscle contraction depends upon a large increase in sarcoplasm Ca+2. The source of this calcium is a the sarcoplasmic reticulum b the t-tubules c the extracellular fluid d tropomyosin e the mitochondria

stem cells that fuse to form each muscle fiber

Skeletal muscle is made up of muscle fibers, which are a syncitium (i.e. multinucleated unit) formed from the fusion of individual myoblasts. What are myoblasts?

deep invaginations of the sarcolemma that extend into the sarcoplasm

Throughout these large multinucleated cells, the sarcolemma forms channels that run into and through the cells called Transverse tubules (T-tubules). What are t-tubules?

1. Z-disk - border of the sarcomere, where actin joins together 2. Actin (thin) filaments 3. Myosin (thick) filaments 4. *Titin* - anchors myosin to the Z-line 5. M-line - center/"middle" of the sarcomere, where myosin joins together 6. H-band - area of just myosin (thick) filaments, "Huge" filaments 7. A-band - entire length of the thick filaments, and a constant area, where actin and myosin overlap 8. I-band - just the thin filaments, "I" is a very thin letter Note: A-band appears "dArker" and I-band appears "lIghter"

Structure of sarcomere

* T tubules are continuous with the sarcolemma * They conduct impulses to the deepest regions of the muscle * These impulses signal for the release of Ca2+ from adjacent terminal cisternae

T tubules function

This delay, referred to as the latent period, is the time it takes for the Ca+2 to increase in the sacroplasm and interact with troponin. Also, the twitch contraction lasts for many tens of milliseconds (say 50-100 milliseconds), as opposed to the ~2 msec for the action potential. This relatively long time of the contraction results from the time it takes to pump the Ca+2 back into the sarcoplasmic reticulum, restoring the very low levels of Ca+2 in the sarcoplasm.

The figure below shows the neuronal action potential and the muscle fiber action potential that results after a very short (<1 msc) delay. The twitch contraction then results. However, note that the twitch contraction is delayed several milliseconds from the action potential. What causes this delay?

skeletal muscle

These muscle fibers are large, multinucleate cells that appear striped or striated under the microscope

cardiac muscle

These muscle fibers are striated but they are smaller, branched, and uninucleate. Cells are joined in series by junctions called intercalated disks

In the myofibril, thin and thick filaments partially overlap and contraction results from the sliding of the filaments along each other. A prominent feature of the banding pattern is the dark Z line (though it is a line when viewed in two dimensions, it extends across the width of the myofibril and should more appropriately be thought about as a Z disk.) Thin filaments are anchored to the Z disk. The smallest contractile unit of muscle is the section of myofibril extending from one Z disk to the next. (As we will see shortly, contraction is the pulling of two Z disks towards each other. This structure bounded by adjacent Z disks is a sarcomer. The I band contains thin filaments but not thick filaments. The A band contains thick filaments. Thin and thick filaments overlap in a portion of the A band, but there is also a portion of the A band that contains thick filaments but not thin filaments and this is referred to as the H zone. In the middle of the sarcomere is the M line (again, think disc), which anchors the the thick filaments. I and A refer to how they scatter light, with the I band looking lighter than the A band

This is the structure of a myofibril. These proteins are present in a highly organized manner, and their assembles in thick and thin filaments repeat in a very regular way along the length of the myofibril to give it a striated appearance. Go through the structure of the myofibril and understand what constitutes the banding pattern. Z disk (line), I band, A band, H zone, M line, what does the I and A refer to, what portion is the sarcomere

3

Thus, under these resting conditions of tropomyosin preventing the binding of actin and myosin, the cross bridge cycle would be stopped at which point in figure 8.8 above?

autonomic

What NS controls smooth muscle?

bundles of myofilaments

What are myofibrils?

contractile proteins (actin and myosin)

What are myofilaments?

it provides the energy to drive the power stroke and it also causes the dissociation of the actin and myosin. (One of these is a process requiring the energy in ATP, the other does not.)

What are the 2 functions of the cross bridge cycle ATP?

1. Hydrolysis of ATP by myosin energizes the cross-bridges, providing the energy for force generation 2. Binding of ATP to myosin dissociates cross-bridges bound to actin, allowing the bridges to repeat their cycle of activity 3. Hydrolysis of ATP by the Ca-ATPase in the sarcoplasmic reticulum provides the energy for the active transport of calcium ions into the reticulum, lowering the cytosolic calcium to prerelease levels, ending the contraction, and allowing the muscle fiber to relax

What are the 3 functions of ATP in skeletal muscle contraction?

1. Skeletal 2. Cardiac 3. Smooth

What are the 3 types of muscle tissue?

Thin filaments are made up of actin, and also to key proteins associated with actin, tropomyosin and troponin (more on them later). Filamentous actin (f-actin) is a polymer of gobular actin (G-actin). Think about a string of balls. Thick filaments are comprised of myosin molecules. The myosin molecule can be though about as having a long filamentous 'tail' region, a more globular 'head' region, and a 'hinge' region that connects the two.

What are thin and thick filaments made of? Describe their appearance

Skeletal muscle is innervated by somatic motor neurons, and it is the input from these motor neurons that causes the initiation of the action potential in the muscle fiber.

What initiates the muscle AP?

Excitation-contraction coupling is the sequence of molecular events that begins with electrical depolarization of muscle fiber and culminates in mechanical contraction 1. AcH released from motor neuron 2. Initiates an AP in the muscle fiber 3. Triggers calcium release from the sarcoplasmic reticulum 4. Calcium combines with troponin and initiates contraction

What is excitation-contraction coupling? What are the steps it proceeds through?

- movement within the external environment - manipulation of external environment - movement of contents through tubes (hollow organs) within the body - exchange of substances between internal and external environments

What is muscle important for?

Contraction

What is muscle specialized for?

muscle fiber

What is the muscle equivalent of a muscle cell?

sarcoplasm

What is the muscle equivalent of the cytoplasm?

sarcoplasmic reticulum

What is the muscle equivalent of the modified ER?

Skeletal muscle, which makes up approximately 80% of our body's muscle mass

What type of muscle is most prevalent in the body?

Both skeletal muscle and cardiac muscle have a striated (banded) appearance under the microscope, but typically the term striated muscle is used to refer to skeletal muscle. (But still, some authors use the term striated muscle synonymously with skeletal muscle.) Smooth muscle lacks the striated appearance.

What type of muscles are striated? Why one isn't?

Smooth muscle and cardiac muscle are not under conscious voluntary control and are typically called involuntary or autonomic muscle.

What type of muscles aren't under voluntary control? What are they referred to as?

Muscles are excitable cells capable of generating action potentials (i.e., they have voltage gated Na channels). the action potential spreading in the muscle fiber causes release of Ca+2 from sarcoplasmic reticulum into the sarcoplasm. A voltage sensitive membrane protein, the dihydropyridine (DHP) receptor, that is coupled to the Ca+2 channel in the sarcoplasmic reticulum through another protein, the ryanodine receptor. (Note, the DHP and ryanodine receptors are not receptors in the way we have been using this term; rather they are proteins that were identified and named by actions of exogenous chemicals.)

What, then, causes Ca+2 to increase in the sarcoplasm?

The amount of acetylcholine release at the neuromuscular junction caused by a single action potential in the motor neuron is sufficient to cause an action potential to be generated in the muscle fiber. This action potential generated in the muscle fiber rapidly spreads through the muscle fiber and along the T tubules. this action potential causes Ca+2 release from the sarcoplasmic reticulum, resulting in contraction.

When an action potential is generated in a motor neuron, it causes release of acetylcholine at the neuromuscular junction which, by acting on nicotinic receptors on the muscle fiber causes it to depolarize. (Why?)

acetylcholine, nicotinic cholinergic

When an action potential is generated in a somatic motor neuron, the neurotransmitter ____ is released at the neuromuscular junction, and it acts on __ receptors.

only in the heart

Where is cardiac muscle found?

It is required for the dissociation of actin from myosin. it supports the Ca++-ATPase that is responsible for pumping Ca++ into the sarcoplasmic reticulum

Which of the following is an important function of ATP in skeletal muscle? a It is required for the dissociation of actin from myosin. b It is used for the phosphorylation of myosin. c It is used for the phosphorylation of tropomyosin. d it binds to the DHP receptor to cause Ca++ release from the sarcoplasmic reticulum e it supports the Ca++-ATPase that is responsible for pumping Ca++ into the sarcoplasmic reticulum

myosin and actin cycle between binding and unbinding

Which of the statements below is most related to the cross-bridge cycle?

Even when ATP is present, the cross bridge cycle stalls at stage 3, the relaxed state. Here, the tropomyosin surrounds the actin and partially blocks the myosin binding sites on the actin. So even though the myosin head is physically cocked and in a high power stage, it can't move the actin bc the tropomyosin is in the way. Tropomyosin is associated with troponin, which is sensitive to calcium, so when calcium is present, it binds to tropomyosin and pulls it away from the myosin binding sites, allowing the cycle to proceed

Why doesnt the cross bridge cycle keep cycling? Where in the cycle is it stopped and how? What then initiates the cross bridge cycle?

Skeletal muscle is also referred to voluntary muscle; it contracts only in response to nerve impulses from somatic motor neurons.

Why is skeletal muscle considered to be under voluntary control?

smooth muscle

these are muscle fibers that are small and lack striations. They are spindle shaped and uninucleate

sarcolemma

what is the muscle equivalent of the cell membrane?