BIO 360 Module 4

The total tension a muscle can develop depends upon two factors:

(1) the amount of tension developed by each fiber, and (2) the number of fibers contracting at any time.

Translated to a whole muscle, these characteristics become the:

1. Load on the whole muscle 2. Types of motor units in the muscle

List the steps of events occuring at the neuromuscular junction:

1. Motor neuron Action potential 2. Ca2+ enters voltage-gated channels 3. ACh is released across the synaptic cleft 4. ACh binds open ion channels 5. Na+ enters 6. Local current occurs between depolarized end plate and adjacent muscle plasma membrane 7. Muscle fiber action potential is initiated 8. Propagation of action potential in muscle plasma membrane 9. ACh degradation

The number of fibers contracting at any time depends on the following factors:

1. The number of fibers in each motor unit (motor unit size) 2. The number of active motor units

The tension decline at lengths less than L0 is the result of several factors. For example:

1. The overlapping sets of thin filaments from opposite ends of the sarcomere may interfere with the cross-bridges' ability to bind and exert force 2. At very short lengths, the Z lines collide with the ends of the relatively rigid thick filaments, creating an internal resistance to sarcomere shortening

Three ways a muscle fiber can form ATP

1. phosphorylation of ADP by creatine phosphate 2. oxidative phosphorylation of ADP in the mitochondria 3. phosphorylation of ADP by the glycolytic pathway in the cytosol

Low-Intensity Exercise:

Exercise that is of relatively low intensity but long duration (popularly called "aerobic exercise"), such as distance running, produces changes in muscle fibers that increase proficiency at that type of activity. These include an increase in the number of mitochondria in all muscle fibers and a shift in myosin composition of fast fibers from type 2X to type 2A. In addition, the number of capillaries around these fibers increases. All these changes lead to an increase in the ability to sustain muscle contraction through oxidative metabolism and thus increased capacity for endurance activity with a minimum of fatigue.

As a person varies their exercise type from a single maximal burst (e.g. lifting the maximal possible weight), to burst performance that lasts under a minute (e.g. sprinting a hundred meters) to a long-term, low intensity exercise (e.g. walking or jogging for two hours), how do the fuels, pathways and end products used to produce ATP differ?

For very short-term maximal exercise, creatine phosphate is used as a very fast supply of ATP. The end product for this reaction is creatine and inorganic phosphate. For a longer-term of still near-maximal exercise like sprinting, glucose (derived from glycogen or blood glucose) is used as a fuel for glycolysis, producing mostly lactate and protons. For long-term, low-intensity exercise such as prolonged walking, glucose is burned for the first 30 min or so, and then fat will be burned aerobically, producing CO2 and water.

Compare the activation of smooth muscle to skeletal muscle.

In smooth muscle, a rise in cytoplasmic Ca++ causes a binding of Ca++ to calmodulin, which associates with myosin kinase, causing a phosphorylation of myosin. The myosin cross-bridge then binds to actin, and cleaves ATP to contract. Relaxation occurs due to a fall in Ca++, which activates myosin phosphorylase, which removes the phosphate from myosin, so it will not bind to actin. In contrast, in skeletal muscle, Ca++ binds to troponin, which regulates the shape of tropomyosin, triggering contraction.

What regulatory molecules mediate exercise-induced changes in muscle?

Insulin-like growth factor-1, Anabolic steroids (androgens) and myostatin.

Does the lever system of most muscles increase the force that muscles can produce on the environment? Explain.

No, muscles operate at a mechanical disadvantage, as they insert a short distance from the fulcrum (joint pivot point) compared to the end of the limb, which acts on the environment. So the force on the environment is less than exerted by the muscle. However, the end of the limb can move faster than the muscle can shorten.

How is smooth muscle different than skeletal muscle? (Select all that apply.) a. In smooth but not skeletal muscle, the thick filament is actin and the thin filament is myosin. b. In smooth but not skeletal muscle, some neurons release inhibitory chemicals. c. In smooth but not skeletal muscle, ATP is needed for myosin to detach from actin. d. Unlike skeletal muscle, smooth muscle cells have a single nucleus and have the capacity to divide throughout the life of an individual.

b, d

The thin filament is made mostly of the protein myosin while the thick filament is made mostly of the proteins actin, troponin, and tropomyosin. True or false? a. True b. False

b. False

List the steps of cytosolic increase in Ca2+

1. Action potential propagated along muscle cell membrane and into T-tubules 2. Ca2+ is released from terminal cisternae 3. Ca2+ binds to troponin and removes the blocking action of tropomyosin 4. Cross-bridges bind, rotate, and generate force 5. Ca2+ is transported back into the sarcoplasmic reticulum 6. Removal of Ca2+ from troponin restores tropomyosin's blocking action

List the steps of the cross bridge cycle

1. Attachment of the cross-bridge to a thin filament 2. Movement of the cross-bridge, producing tension in the thin filament 3. Detachment of the cross-bridge from the thin filament 4. Energizing the cross-bridge so it can again attach to a thin filament and repeat the cycle

Compare the control of smooth muscle contractile activity to skeletal muscle.

The inputs that influence smooth muscle contractile activity are extremely varied, including spontaneous electrical activity in the plasma membrane of the muscle cell, various neurotransmitters released by autonomic neurons, hormones, local induced changes in the chemical composition of the extracellular fluid surrounding the cell, and stretch. Some of these inputs can inhibit smooth muscle contraction, while others stimulate contraction. In contrast, with skeletal muscle, there is only excitatory stimuli, when motor neurons release acetylcholine.

The velocity at which a single muscle fiber shortens is determined by the following factors:

1. The load on the fiber 2. The speed of the myosin type expressed in the fiber

Two sources of Ca2+ contribute to the increase in cytosolic Ca2+ that initiates smooth muscle contraction:

1. The sarcoplasmic reticulum 2. Extracellular Ca2+ entering the cell through plasma membrane Ca2+ channels

Acute muscle fatigue results in metabolic changes such as a decrease in ATP concentration and increases in the concentrations of ADP, Pi, Mg2+, H+ (from lactic acid), and oxygen free radicals. This results in:

1. decrease the rate of Ca2+ release, reuptake, and storage by the sarcoplasmic reticulum 2. decrease the sensitivity of the thin filament proteins to activation by Ca2+ 3. directly inhibit the binding and power-stroke motion of the myosin cross-bridges

Select the TRUE statement. a. Only humans use actin and myosin to move. b. Only mammals use actin and myosin to move. c. Only animals use Myosin and actin to move. d. Animals and some unicellular organisms use actin and myosin to move.

d.

Sequence of Events Between a Motor Neuron Action Potential and Skeletal Muscle Fiber Contraction:

1. Action potential is initiated and propagates to motor neuron axon terminals. 2. Ca2+ enters axon terminals through voltage-gated Ca2+ channels. 3. Ca2+ entry triggers release of ACh from axon terminals. 4. ACh diffuses from axon terminals to motor end plate in muscle fiber. 5. ACh binds to nicotinic receptors on motor end plate, increasing their permeability to Na+ and K+. 6. More Na+ moves into the fiber at the motor end plate than K+ moves out, depolarizing the membrane and producing the end-plate potential (EPP). 7. Local currents depolarize the adjacent muscle cell plasma membrane to its threshold potential, generating an action potential that propagates over the muscle fiber surface and into the fiber along the T-tubules. 8. Action potential in T-tubules induces DHP receptors to pull open ryanodine receptor channels, allowing release of Ca2+ from terminal cisternae of sarcoplasmic reticulum. 9. Ca2+ binds to troponin on the thin filaments, causing tropomyosin to move away from its blocking position, thereby uncovering cross-bridge binding sites on actin. 10. Energized myosin cross-bridges on the thick filaments bind to actin: 11. Cross-bridge binding triggers release of ATP hydrolysis products from myosin, producing an angular movement of each cross-bridge: 12. ATP binds to myosin, breaking linkage between actin and myosin and thereby allowing cross-bridges to dissociate from actin: 13. ATP bound to myosin is split, energizing the myosin cross-bridge: 14. Cross-bridges repeat steps 10 to 13, producing movement (sliding) of thin filaments past thick filaments. Cycles of cross-bridge movement continue as long as Ca2+ remains bound to troponin. 15. Cytosolic Ca2+ concentration decreases as Ca2+-ATPase actively transports Ca2+ into sarcoplasmic reticulum. 16. Removal of Ca2+ from troponin restores blocking action of tropomyosin, the cross-bridge cycle ceases, and the muscle fiber relaxes.

Functions of ATP in Skeletal Muscle Contraction

1. Hydrolysis of ATP by the Na+/K+-ATPase in the plasma membrane maintains Na+ and K+ gradients, which allows the membrane to produce and propagate action potentials. 2. Hydrolysis of ATP by the Ca2+-ATPase in the sarcoplasmic reticulum provides the energy for the active transport of calcium ions into the reticulum, lowering cytosolic Ca2+ to prerelease concentrations, ending the contraction, and allowing the muscle fiber to relax. 3. Hydrolysis of ATP by myosin-ATPase energizes the cross-bridges, providing the energy for force generation. 4. Binding of ATP to myosin dissociates cross-bridges bound to actin, allowing the bridges to repeat their cycle of activity.

Three types of muscle fibers:

1. Slow-oxidative fibers (type 1) combine low myosin-ATPase activity with high oxidative capacity. 2. Fast-oxidative-glycolytic fibers (type 2A) combine high myosin-ATPase activity with high oxidative capacity and intermediate glycolytic capacity. 3. Fast-glycolytic fibers (type 2X) combine high myosin-ATPase activity with high glycolytic capacity.

Functions of ATP in cross-bridge cycling:

1. The energy released from ATP hydrolysis ultimately provides the energy for cross-bridge movement. 2. ATP binding (not hydrolysis) to myosin breaks the link formed between actin and myosin during the cycle, allowing the next cycle to begin.

The neural control of whole-muscle tension involves the following:

1. The frequency of action potentials in individual motor units (to vary the tension generated by the fibers in that unit) 2. The recruitment of motor units (to vary the number of active fibers)

What is the difference between twitch, tetanus and unfused tetanus? Why is the tension generated greater during tetanus than twitch?

A twitch contraction is the mechanical result of a single action potential and the tension will decrease after the twitch. Tetanus is where repeated twitch contraction at a rate faster than the tension can return to zero causes a maintained contraction with high constant tension. Unfused tetanus is like tetanus except that the rate of twitch contractions is slower and this leads to a fluctuation in the tension of the continuous contraction. Higher tensions are generated during tetanus for a number of reasons. First, during tetanus, cytoplasmic calcium levels reach higher levels as more calcium exits the sarcoplasmic reticulum (SR) due to repeated stimulations than can be pumped into the SR by the calcium ATPase. Higher calcium levels mean that more calcium is bound to troponin, allowing more sites on actin to be available to the myosin cross-bridges. Also, Elastic elements such as tendons and titin tend to absorb more of the tension during a twitch than during tetanus.

How does an acetylcholinesterase inhibitor (as found in some nerve gases and organophosphate insecticides) cause paralysis?

Acetylcholinesterase in an enzyme found in the synapse at the neuromuscular junction, as well as at muscarinic synapses. Acetylcholinesterase breaks down acetylcholine after it has been released and/or is bound to the receptor, stopping the stimulation. If acetylcholinesterase is inhibited, the acetylcholine stays bound to the receptor. The muscle (or postsynaptic neuron) cannot repolarize, so briefly, the muscle is in a prolonged contraction. Over time, the receptor stops responding to the bound acetylcholine, and the muscle is paralyzed. Death occurs because the respiratory muscles are paralyzed, and oxygen cannot be delivered to the lungs.

Give examples of skeletal muscle disorders which target the central nervous system, peripheral nervous system and muscle tissue respectively. Explain the mode of action for each disorder.

An example of a skeletal muscle disorder that occurs in the central nervous system would be poliomyelitis. Poliomyelitis is a viral disease that destroys motor neurons. This leads to paralysis of skeletal muscle and possibly death due to respiratory failure. An example of a skeletal muscle disorder that occurs in the peripheral nervous system would be muscle cramping. Though the specific cause of muscle cramps is uncertain, that are partly caused by electrolyte imbalances in the extracellular fluid surrounding both the muscle and the nerve fibers or axons. The axons of motor neurons are located in the peripheral nervous system. Finally examples of a skeletal muscle disorders that occurs in the muscle tissue include Hypocalcemic tetany that is caused by a decrease in extracellular Ca2+ which leads to membrane depolarization and spontaneous firing of action potentials in increased muscle contractions. Muscular Dystrophy which is caused by the absence of defect of one or more proteins that make up costameres (clusters of structural and regulatory proteins linking the Z disks to the sarcolemma and extracellular matrix) in striated muscle. Finally the autoimmune disease, Myasthenia gravis that causes progressively worsening muscle fatigue and weakness. Antibodies from the immune system target and destroy nicotinic ACh-receptor proteins of the motor end plate making muscle cells less responsive to action potential firings from motor neurons.

The following sequence of events occurs after an increase in cytosolic Ca2+ in a smooth muscle fiber:

Ca2+ binds to calmodulin, a Ca2+-binding protein that is present in the cytosol of all cells and whose structure is related to that of troponin. The Ca2+-calmodulin complex binds to another cytosolic protein, myosin light-chain kinase, thereby activating the enzyme. Active myosin light-chain kinase then uses ATP to phosphorylate myosin light chains in the globular head of myosin. Phosphorylation of myosin drives the cross-bridge away from the thick filament backbone, allowing it to bind to actin. Cross-bridges go through repeated cycles of force generation as long as myosin light chains are phosphorylated.

High-Intensity Exercise:

In short-duration, high-intensity exercise (popularly called "strength training") such as weight lifting, primarily the fast-twitch fibers are recruited. These fibers undergo an increase in diameter (hypertrophy) due to satellite cell activation and increased synthesis of actin and myosin filaments, which form more myofibrils. The myosin expressed in fast fibers shifts from type 2A toward the faster and more powerful type 2X. In addition, glycolytic activity is increased by increasing the synthesis of glycolytic enzymes. The result of such high-intensity exercise is an increase in the strength of the muscle and the bulging muscles of a conditioned weight lifter. Such muscles, although very powerful, have little capacity for endurance and they fatigue rapidly. It should be noted that not all of the gains in strength with resistance exercise are due to muscle hypertrophy. It has frequently been observed, particularly in women, that strength can almost double with training without measurable muscle hypertrophy. The most likely mechanisms are modifications of neural pathways involved in motor control. For example, regular weight training is hypothesized to cause increased synchronization in motor unit recruitment, enhanced ability to recruit fast-glycolytic motor neurons, and a reduction in inhibitory afferent inputs from tendon sensory receptors.

What is the difference between isometric and isotonic contraction?

Isometric contraction is when a muscle fiber develops tension without changing the length of the muscle fiber. Isotonic contraction is when a muscle fiber maintains a constant tension while changing the length of the muscle fiber.

Why is skeletal muscle referred to as striated muscle?

Skeletal muscle is referred to as striated muscle because the myofibrils of each muscle cell are made up of a repeating pattern of cellular structures known as the sarcomere that, from a microscopic view, forms light and dark bands perpendicular to the long axis.

What are the structural differences between skeletal muscle and smooth muscle?

Smooth muscle cells are much smaller than skeletal muscle fibers. Smooth muscle cells have a single nucleus and have the capacity to divide throughout the life of an individual. Regulatory protein troponin is absent in smooth muscle and a protein called caldesmon associates with the thin filaments of smooth muscle. The thin filaments are anchored either to the plasma membrane or to cytoplasmic structures known as dense bodies in smooth muscle cells. The filaments are organized diagonally to the long axis of the smooth muscle cells and the filaments are not organized in myofibrils nor do they contain sarcomeres. The concentration of myosin in smooth muscle is about one-third that of skeletal muscle and the actin concentration can be twice that of skeletal muscle. Smooth muscle can maintain more tension production when its length is greatly increased than skeletal muscle can.

How does the length of a muscle fiber effect the tension of a contraction?

The relationship of the overlap of the thick and thin filaments affects the tension of a contraction since the sliding-filament mechanism is what creates the tension. If there is so much overlap that the thick filament can't physically pull the thin filament any farther, the tension will be low. As the length increases there will be more area for the thick filament to pull on the thin filament. As the fiber is continued to be lengthened, there will be a point where the amount of overlap of the thick and thin filament will decrease and this will cause the tension to decrease as well.

What are the proteins that make up the thick and thin filament? Which molecule forms the cross-bridge?

The thick filament is composed of myosin filaments, and myosin forms the crossbridges. The thin filament is composed of actin filaments, which are wrapped with tropomyosin filaments, and studded with troponin molecules.

You see a weightlifter curling heavy weights. This makes you notice the difference in muscle mass between yourself and the weightlifter. How do muscles increase in size in response to their heavy exercise practices?

The weightlifter has most likely undergone muscle hypertrophy. This muscular hypertrophy likely occurred by a combination of enlargement of existing muscle fibers, splitting of existing muscle fibers, and satellite cell proliferation, differentiation, and fusion.

Select the TRUE statement(s) about single unit smooth muscle. (Select all that apply.) a. Has most cells connected by gap junctions b. Has the property that most of the cells contract together c. An example is the smooth muscle of the uterus d. Are controlled by somatic motor neurons

a, b, c

You are contracting your bicep muscle to create tension applied to an object you are holding. The object you are holding is placing a load on your muscle. You are not able to hold the object up because it is too heavy and you are slowly dropping the object. What will happen? (Select all that apply.) a. Your bicep muscle is experiencing an isotonic contraction b. Your bicep muscle is undergoing an eccentric contraction c. The tension exerted by the biceps exceeds the load. d. The load is greater than the maximum isometric tension

a, b, d

You stepped on a rusty nail and contracted the tetanus toxin from Clostridium tetani. The toxin blocks the inhibitory nerve terminals in your motor neurons causing all motor neurons to fire at high rates. What will happen to your muscles? (Select all that apply.) a. The skeletal muscles will exhibit tetanus (sustained contractions). b. Ca2+ levels in skeletal muscle cytoplasm will be at a sustained high level. c. Troponin levels in muscle will increase. d. Skeletal muscles will produce greater tension than during a twitch.

a, b, d

Select the TRUE statement(s) about smooth muscle. (Select all that apply.) a. Norepinephrine released from the sympathetic nervous system can inhibit peristalsis in gut smooth muscle. b. Some smooth muscle cells spontaneously depolarize and contract. c. Smooth muscle uses ATP more rapidly than skeletal muscle. d. A drug that activates myosin phosphorylase will trigger contraction.

a, b.

As you lift a heavier weight, what is happening? (Select all that apply.) a. You increase the number of muscle fibers activated in each motor unit. b. You increase the number of motor units that are active in each activated muscle. c. You increase the frequency of action potentials in your motor neurons. d. You increase the diameter of muscle fibers activated in a motor unit.

a, d

Which fiber type is most dependent on glycogen as a fuel source during exercise? a. Red oxidative b. Fast glycolytic c. Fast oxidative glycolytic d. Red oxidative and fast glycolytic both are equally highly dependent on glycogen as a fuel

b. Fast glycolytic

What is true about muscular dystrophy? (Select all that apply.) a. Muscular dystrophy is a genetic disease. b. Muscular dystrophy occurs when the host's immune system targets and breaks down structural proteins in myofibrils. c. The negative effects of muscular dystrophy can be mitigated with the administration of acetylcholinesterase inhibitors. d. Muscular dystrophy is caused by the absence or defect of one or more proteins that link the z disks to the sarcolemma.

a, d

Botulism is caused by the bacterium Clostridium botulinum, and the toxin from this bacteria is the active ingredient in botox. Which statement(s) is/are TRUE about botulism? (Select all that apply.) a. Botulinum toxin breaks down proteins of the SNARE complex in the axon terminal, stopping acetylcholine release. b. Botulinum reduces the amount of acetylcholine bound to the receptor. c. Botulinum binds strongly to nicotinic ACh receptors. d. Botulinum toxin inhibits the voltage-gated sodium channel.

a. Botulinum toxin breaks down proteins of the SNARE complex in the axon terminal, stopping acetylcholine release. b. Botulinum reduces the amount of acetylcholine bound to the receptor.

Select the statements that apply to high endurance performers in the Animal Kingdom. (Select all that apply.) a. Fast muscle contraction speed. b. Fat is the primary fuel used. c. Lactate production is high. d. A hyena is an example of a high endurance performer. e. Mitochondrial content is high.

b, d, e

A drug that blocked calcium release from the sarcoplasmic reticulum of smooth muscle would most likely ___________. a. stop contraction of smooth muscle b. reduce the contraction of smooth muscle c. have no effect on contraction of smooth muscle d. stimulate the contraction of smooth muscle

b.

What is the correct sequence of events for cross-bridge activation in smooth muscle? A. The Ca2+-calmodulin complex binds troponin and removes blocking action of tropomyosin. B. Phosphorylation of myosin drives the cross-bridge away from the thick filament backbone, allowing it to bind to actin. C. Ca2+ removal from troponin restores tropomyosin blocking action D. Ca2+ binds to calmodulin. E. Active myosin light-chain kinase phosphorylates myosin light chains. F. Cross-bridges go through repeated cycles of force generation as long as myosin light chains are phosphorylated. G. The Ca2+-calmodulin complex binds myosin light-chain kinase. a. A,D,E,F,C b. D,G,E,B,F c. D,A,E,F,C d. A,D,E,B,F

b.

Refer to the figure above. Why does the overall isometric tension of a stimulated muscle fiber drop as the muscle fiber length is increased past the optimal length (L0)? a. Fiber length at length 4 in the diagram is the longest length a fiber can be stretched. So by increasing length beyond length 4, the muscle fiber is torn and overall tension decreases. b. Filament overlap is near-ideal at length 4, stretching the fiber beyond that drops the maximal number of cross-bridges able to bind to the thin filaments, thereby decreasing the overall tension. c. The tension exerted at length 2 is less than at length 4 because at length 4 the actin and myosin fibers are more stretched. d. Filament overlap is ideal at length 4 for isotonic tension but not isometric tension. Stretching the fiber beyond (L0) is therefore keeping the tension the same while changing the length.

b. Filament overlap is near-ideal at length 4, stretching the fiber beyond that drops the maximal number of cross-bridges able to bind to the thin filaments, thereby decreasing the overall tension.

A drug that blocked calcium uptake by the sarcoplasmic reticulum calcium ATPase would have what effect? a. The muscle would always be relaxed. b. The muscle would show a prolonged contraction. c. The muscle would be in rigor mortis. d. The membrane potential would be depolarized.

b. The muscle would show a prolonged contraction.

Cutting a motor neuron is likely to cause _______. a. one muscle cell will no longer contract b. multiple muscle cells will no longer contract c. one muscle cell with contract and stay contracted d. multiple muscle cells will contract

b. multiple muscle cells will no longer contract

Acetylcholine (ACh) is the neurotransmitter used by motor neurons. Which statement is TRUE about ACh at the neuromuscular junction? a. ACh enters the muscle fiber through the motor end plate, depolarizing the sarcolemma. b. ACh in the neuromuscular junction produces an inhibitory postsynaptic potential (IPSP). c. ACh binds to metabotropic receptors of the nicotinic type. d. ACh is broken down in the synaptic cleft by acetylcholinesterase and transported back into the axon terminals as choline.

d. ACh is broken down in the synaptic cleft by acetylcholinesterase and transported back into the axon terminals as choline.