Skeletal Muscle

Question 1

Why does the alpha-motorneuron act as the final common pathway for motor unit activation?

Answer 1

It integrates excitatory and inhibitory inputs

Question 2

Botulinum toxin (Botox) prevents release of Ach from the motoneuron, resulting in what?

Answer 2

decreases the magnitude of the graded depolarization in the neuromuscular junction

Question 3

Skeletal muscle is innervated by motorneurons from where?

Answer 3

ventral horn of the spinal cord. The axon of these motorneurons diverges in the skeletal muscle bed to innervate multiple muscle fibers.

Question 4

T or F. Each muscle fiber receives innervation from only one motorneuron.

Answer 4

T.

Question 5

What is the main role of the motoneuron body?

Answer 5

It acts as an integrator of excitatory and inhibitory synapsesimpinging upon its cell membrane, and thus acts as a Final Common Pathway for muscle fiber contraction.

Question 6

The motorneuron and the muscle fibers that it innervates are called a_____.

Answer 6

motor unit. When the motorneuron generates an action potential, all fibers within the motor unit will contract.

Question 7

What are the types of motoneuron cell bodies?

Answer 7

large and small

Question 8

Describe small motoneuron cell bodies.

Answer 8

In general, these motorneurons will innervate relatively few muscle fibers. Thesemuscle fibers also have a tendency to have relatively small cross-sectional diameters.Such motor units are routinely referred to as slow motor units because of theirmechanical characteristics. In contrast, large motoneuron bodies innervate many and are called fast motor units

Question 9

What happens when an action potential reaches the nerve terminal?

Answer 9

Ach is released fromsynaptic vesicles into the synaptic cleft through normal, Ca2+-mediated synaptictransmission.

Question 10

What is the target for the released acetylcholine?

Answer 10

Nicotinic M acetylcholinereceptors in the motor end-plate on the muscle.

Question 11

Describe nicotinic Ach receptors.

Answer 11

monovalent cation channels (for Na+ AND K+), so activation of these channels will generate a graded depolarization.The motor end-plate is very dense with nicotinic acetylcholinereceptors and has very few voltage-gated sodium channels.

Question 12

What must occur for activation of the voltage-gated sodium channels that residein the surrounding membrane around the nicotinic receptors?

Answer 12

a sufficient number of receptors must be activated in order to bring the surrounding membrane abovethreshold for an action potential

Question 13

What happens once an action potential is reached?

Answer 13

an action potential is initiated that propagates along the muscle fiber membrane as it would in an unmyelinated nerve axon

Question 14

What conducts the membrane depolarization along the muscle fibers toward the SR?

Answer 14

T(transverse)-tubules

Question 15

What does depolarization of the T-tubule membrane cause?

Answer 15

The depolarization of the T-tubule membrane has the effect of causing a conformationchange in the dihydropyridine receptor

Question 16

What does the change in conformation of the dihydropyridine receptor do?

Answer 16

In skeletal muscle, this activates a calcium channel in the SR, the ryanodine receptor

Question 17

What does opening of the ryanodine receptor cause?

Answer 17

Opening of this calcium channel allow the passive efflux of calcium from the SR store, rapidly elevating intracellular Ca2+ concentration.

Question 18

The unit from one Z-line to the next is called what?

Answer 18

a sarcomere

Question 19

What are thick filaments proteins?

Answer 19

myosin heavy chains, large proteins with a filamentous tail and a globular head, along with two light chains per head

Question 20

How are myosin heavy chains typically composed?

Answer 20

Myosin heavy chains tend to form dimers, and these dimers form the bipolar thick filament with globular headsdirected outward and the heavy chains on one end of the filament aligned in the oppositedirection from those at the other end of the filament.

Question 21

What is the major protein of thin filaments?

Answer 21

actin (and tropomyosins and troponins)

Question 22

What shape do actin filaments take on?

Answer 22

helical chains under the correct conditions Each actinmonomer has a high-affinity binding site for the myosin heads.

Question 23

What is the role of tropomyosins?

Answer 23

These are fibrous proteins that extend along the length of the thin filament such that tropomyosin can cover the myosin binding sites on the actinmolecules

Question 24

What is the structure of troponin molecules?

Answer 24

They form a ternary complex of troponin C, a calcium binding protein, troponin T, a tropomyosin binding protein, and troponin I, a protein that keeps the troponin complex in a position such that tropomyosin covers the myosin binding site on the actin molecules when calcium is not present in sufficiently high concentrations.

Question 25

How is tropomyosin arranged when Ca2+ levels are low?

Answer 25

such that there cannot be myosin-actin interaction.

Question 26

What happens when Ca2+ is released from the SR?

Answer 26

calcium binds to troponin C, causing a conformation change that moves the tropomyosin deeper into the helical cleft of the fibrous actin. This uncovers the binding site for myosin on actin,allowing myosin to interact and produce force.

Question 27

How is force produced from myosin interacting with actin?

Answer 27

the ATPase activity in the myosin head consumes energy to produce a mechanical force.

Question 28

Specifically, how is forced generated?

Answer 28

When ATP has been hydrolyzed and the resulting ADP remains bound to the myosin head, the myosin head goes into a high affinity state for binding actin.

Question 29

What is the ‘hinge’?

Answer 29

Once bound to actin, a conformation change takes place near where the globular head and fibrous tail of the myosin heavy chain connect, the so-called hinge

Question 30

What is the result of the conformation change resulting in the hinge?

Answer 30

The conformation change has the effect of attempting to pull the thick filament toward the Z-line. Because the thick filament is bipolar, the net effect is to draw the Z-lines toward one another. This is called the power stroke.

Question 31

T or F. Myosin and actin will remain bound to one another as long as ADP is bound to the myosin head

Answer 31

T.

Question 32

What happens to myosin affinity for ADP once the power stroke occurs?

Answer 32

the myosin head has a much higher affinity for ATP, so ATP displaces ADP, lowering the myosin-actin affinity and allowing the myosin head to release.ATP is then hydrolyzed and the cross-bridge cycling begins again. In response to a single action potential, only a few cross-bridge cycles occur.

Question 33

What causes rigor mortis?

Answer 33

The inability to actively pump calcium back into the SR along with the inability to release the myosin-actin cross-bridge (both due to lack of ATP)

Question 34

What is peak tension?

Answer 34

Attaching a muscle, or muscle fiber, to an apparatus in which we can adjust the length reveals that muscle exerts a passive tension in the absence of any contractile activity. This is much like a rubber band, with intracellular and extracellular proteins providing an elastic force that opposes an increase in length. If the muscle is adjusted to a set length and an action potential is initiated, the peak tension measured will be the sum of the passive tension and the active tension due to myosin-actin interaction.

Question 35

T or F. The active tension has a maximum at aspecific, optimal length.

Answer 35

T.

Question 36

What occurs at the optimal sacromere length?

Answer 36

every myosin head can contribute force. Also note that the passive tension of the muscle or its fibers reaches nearly zero at theoptimum length (where active tension is highest).

Question 37

What is a twitch?

Answer 37

the isometric mechanics of themuscle to a single action potential

Question 38

What is the half-relaxation time?

Answer 38

the time required to relax to one-half the peak isometric tension using a tension transducer

Question 39

How would ryanodine poisoning present?

Answer 39

muscle cramps

Question 40

During routine physical exam of a new patient you note normal muscle reflex contraction but slow muscle reflex relaxation. You ask whether the patient has hypothyroidism. Why?

Answer 40

Slows calcium uptake by the SR via gene changes in ATPase expression

Question 41

T or F. For any given force, fast motor units will developgreater velocity of shortening.

Answer 41

T. Likewise, for any given velocity of shortening, fast motor units will develop greater force.

Question 42

Why is the maximal velocity of shortening more in fast units?

Answer 42

Due to the expression of myosin with more rapid kinetics of cross-bridge cycling

Question 43

Which sized motor neurons are recruited faster for action?

Answer 43

Because of the smaller surface area of a smaller motorneuron body, on average these motorneurons require fewer active excitatory synapses in order for a threshold depolarization to occur in the axon hillock.

Question 44

What is tetanic tension?

Answer 44

the tension produced by the slow motor unit eventually reaches a maximum. Also note that this tetanic tension is greater than the twitch tension.

Question 45

T or F. Slow motor units produce a tetanic contraction at a frequency of activation that is less than for fast motor units.

Answer 45

T. It is also clear that slow motor units produce less tetanic force than fast motor units.

Question 46

Velocity of shortening is directly related to what?

Answer 46

myosin ATPase activity (greater in fast motor neurons)

Question 47

How is ATP regenerated from ADP on myosin heads?

Answer 47

creatine-P is converted to creatine by creatine kinase

Question 48

High creatinine with normal CK and LDH suggests what?

Answer 48

kidney disease decreased clearance

Question 49

High creatinine with elevated CK and LDH suggests what?

Answer 49

muscle disease causing overproduction

Question 50

Describe metabolism of slow motor units.

Answer 50

The muscle fibers have a high mitochondrial density andare rich in myoglobin, producing ATP by oxidative phosphorylation.

Question 51

Are slow motor units susceptible to fatigue?

Answer 51

Because the myosin expressed in these muscle fibers consumes ATP at a relatively slow rate, these fibers are unlikely to be impaired in their ability to produce sufficient energy to produce sustainedcontraction. These slow, oxidative motor units are found in postural muscle.

Question 52

Describe metabolism of fast motor units.

Answer 52

These have muscle fibers whose metabolism is almost entirely glycogenolytic. Because the myosin expressed in these muscle fibers consumes ATP rapidly, and the storage of glycogen is limited, these fast, glycogenolytic fibers rapidly reach a point where contraction cannot be sustained (fatigue).

Question 53

T or F. Motor units, and the fibers within the motor units, are very plastic with respect to their gene expression in response to use and disuse.

Answer 53

T. Adaptations in gene expression tend tofavor economy of energy expenditure to perform tasks.

Question 54

How do motor units adapt to resistance tasks (high energy use)?

Answer 54

increases muscle fiber diameter, shifts toward more fast myosin expression, and increases glycogenolytic metabolism

Question 55

How do motor units adapt to endurance tasks (low energy use)?

Answer 55

favor changes in geneexpression that shift toward slow myosin expression and more oxidative metabolism and muscle fiber size doesnt change much

Question 56

T or F. Our postural muscles, which are used imperceptibly all day, every day forwhat is really an endurance task, will rapidly adapt to a condition of disuse.

Answer 56

T.

Question 57

What adaptations are made with decreased activity (hypokinesia)?

Answer 57

This adaptation shifts the gene expression profile to resemble an atrophied fast motor unit- decreased muscle size, increased contraction velocity, more glycogenolytic. These motor units become more susceptible fatigue, even within a few days of lack of activity.