Muscle Physiology

What four things does the controlled contraction of muscle allow for?

1) purposeful movement of the whole body and parts of the body

2) manipulation of external objects

3) propulsion of contents through various hollow internal organs

4) emptying contents of certain organs to the external environment

What are the three types of muscles and list whether or not they are striated and involuntary/voluntary.

1) skeletal

• striated and voluntary

2) cardiac

• striated and involuntary

3) smooth

• unstriated and involuntary

What causes the striation of muscle?

caused by myosin (dark thick filament) and actin (light thin filament) organization

Instead of troponin what does smooth muscle use?

calmodulin

What are some unique characteristics about the appearance of cardiac muscle?

• branch

• connected with intercalated disk

What are some defining characteristics of skeletal muscle cells?

• many mitochondria

• multinucleated (multiple nucleus per cell since some cells can be huge meaning that different parts of the same muscle fiber have different amounts of varying proteins)

• has transverse tubules

• arranged through myofibrils and sarcomeres, large, elongated, and cylindrically shaped

• fibers extend entire length of muscle

• have specific terms for some of their intracellular structures

  • sarcolemma = plasma membrane

  • sarcoplasm = cytoplasm

  • sarcoplasmic reticulum = smooth ER

What is the neuromuscular junction?

special synapse where motor neurons meet up with skeletal muscle fibers

What are the steps involved within the neuromuscular junction?

1) neuron is stimulated and action potential propagates into the terminal buttons

2) depolarization of the terminal button opens Ca2+ channels

3) Ca2+ ions trigger vesicles of ACh to fuse with the plasma membrane of the neuron

4) ACh diffuses across the synaptic cleft and binds with receptors in the motor end plate (fiber)

5) ACh binding opens the Na+ channel in the motor end plate, leading to the depolarization of the end plate

6) depolarizing current flows to adjacent membrane that contains and activates more Na+ channels

• Na+ influx trigger muscle action potentials allowing for contraction

7) ACh is degraded by ACh-esterase, terminating the action of ACh, closing Na+ channels allowing the muscle to rest

List from largest to smallest the structure of skeletal muscle.

skeletal muscle → muscle fiber → myofibril → sarcomere → thick myosin filaments → thin actin filaments

What is a sarcomere?

the smallest unit of a muscle that can contract and ranges from Z line to Z line, consisting of overlapping proteins

What is muscle?

population of elongated muscle fibers held together by connective tissue and connected at either end by tendons

What are myofibrils?

elongated, cylindrically shapped contractile elements composed of a population of sarcomeres connected end to end that make muscle fiber

What is the T-tubule?

an extension of the membrane through the muscle cell and it is also surrounded by the sarcoplasmic reticulum, both ultimately surrounding myofibrils

What is the M line?

extends vertically down middle of A band within center of H zone, and is made up of proteins

What is the H zone?

lighter area in the middle of A band where thin filaments don’t reach

What is the A band?

made up of thick filaments along with the portions of thin filament that overlap it

What is the I band?

consists of remaining portion of thin filaments that do not project onto A band, typically ranges from two sarcomeres

What is the Z line?

defines boundary of sarcomere, and it is the site where thin filaments attach

What is titin?

largest protein in our body that attaches myosin to the Z-line, keeping myosin in place acting like a spring to ensure that myosin doesn’t move around too much

What is thick filament composed of?

hundred of myosin protein molecules organized into elongated fibers

What is myosin?

• a cytoskeletal protein composed of two interwomen subunits placed opposite of each other. Each unit has a long tail and a globular head region

• head of myosin has two binding sites

  • actin binding site: specialized to bind with actin

  • myosin ATPase: specialized region capable of ATP hydrolysis with the presence of Mg2+

What three things are thin filament composed of?

1) actin (circular)

2) tropomyosin (thread like)

3) troponin (tiny and circular with three subunits)

all are arranged to form an elongated double helical strand

What is actin?

globular cytoskeletal protein linked to form two long chains arranged in a double helical strand

• G actin: monomer

• F actin: polymer

What is tropomyosin?

pairs of threadlike filamentous proteins that lie alongside the grooves formed by the actin helix

What do each of the three subunits of troponin bind to?

1) troponin I: inhibitory subunit that binds to actin

2) troponin T: binds to tropomyosin

3) troponin C: binds to calcium

What are the four steps associated with cross bridge activity?

1) binding:

• myosin cross bridges binds to actin molecules

2) power stroke:

• cross bridge bends, pulling thin filaments inward

3) detachment:

• cross bridge detaches at end of power stroke and returns to original conformation

• lack of this detachment can result in rigor

4) binding:

• cross bridge binds to more distal actin molecules and the cycle repeats

Why is Ca2+ important when talking about cross bridge activity?

binding of Ca2+ to troponin allows for the deactivation of regulatory troponin and tropomyosin (troponin-tropomyosin complex) that block actin binding sites

During muscle contraction describe the changes occuring with the different zones of the sarcomere.

overall sarcomere shortens

• H zone becomes shorter

• I band becomes shorter

• A band remains the same width

• individual actin and myosin fibers maintain a constant length

Why is ATP important for the cross bridge cycle?

its breaks the linkage between myosin and actin allowing for either relaxation of the muscle or for the cross bridge cycle to continue

Explain the varying levels of strength of the cross bridge activity with ATP, ADP, or Pi are bound to myosin

• ADP bound (+ energy): strongest interaction

• ADP + Pi (+ energy) : second strongest

• ATP: weakest, will be detached

What are transverse/T Tubules?

inbagination of the plasma membrane at each sarcomere that supply muscles and initiate muscle contraction

• contain dihydropyridine receptors (Ca2+ voltage gated channels)

What is the sarcoplasmic reticulum?

it’s a modified endoplasmic reticulum composed of a fine network of interconnected tubules in which Ca2+ is stored and actively transported upon stimulation

• lateral sacs is an enlarged region of the sarcoplasmic reticulum that come into close contact with the transverse tubules

What receptor is located on lateral sacs of the sarcoplasmic reticulum?

foot proteins/ryanodine receptors

What are foot proteins/ryanodine receptors?

proteins that span the gap between lateral sacs and transverse tubules and mediate a change in permeability to Ca2+ by the lateral sacks upon stimulation

Explain how an action potential propagated from the motor end plate results in the release of Ca2+.

action potentials from the neuromuscular junction propagate to the T tubules, propagation opens the dihydropyridine receptors as well as the foot proteins/ryanodine receptors connected to the sarcoplasmic reticulum. Since these channels are open, Ca2+ stored in the sarcoplasmic reticulum flow through the foot protein and enter the cytosol of the muscle fiber bind to troponin to start the cross bridge cycling

• relaxing muscles when there’s no more action potentials, aka taking Ca2+ back into the sarcoplasmic reticulum requires energy

Explain the steps in the power stroke.

1) ATP is split by the ATPase binding site on the myosin head resulting in energy, ADP and Pi being stored at the cross bridge

2) Ca2+ is released upon excitation, moving the inhibitory influence on actin

3) Power stroke of cross bridge

4) Pi is released

5) ADP is released

6) energy is released

7) linkage between actin and myosin breaks as fresh ATP binds to myosin again to start the cycle over

What is the important thing to note about the role of ATP in muscle contraction?

ATP is not needed for binding, rather it’s needed for detachment of myosin and actin

• ADP, Pi, and energy are needed for binding

What is a motor unit?

a motor neuron and all of the muscle fiber it innervates, when this neuron is activated, all the muscle fibers it innervates are contracted simultaneously

• one motor neuron connects to and activates multiple muscle muscles fibers, each muscle fiber is supplied by only one motor neuron

Compare and contrast the difference between the amount of motor fibers per motor neuron when look at muscles that produce precise movements versus in muscles that produce powerful movement.

muscles that produce precise, delicate, movements

• contain fewer fibers per motor unit

muscles that produce powerful, coarsely controlled movement

• contain a larger number of fibers per motor unit

the amount of motor units and muscle fiber per unit depend on the specific function of the muscle

What is motor unit recruitment?

the process of increasing the number of motor units that participate in a muscle contraction

• weak contractions: only a few motor units are activated

• stronger contractions: more and more units are recruited

What two things influence muscle tension?

1) number of motor units recruited

2) tension developed by each contracting fiber

What four factors influence tension in a fiber?

1) frequency of stimulation (ex: twitch summation, and tetanus)

2) length of the fiber before contraction (there is an optimal resting length)

3) extent of fatigue

4) thickness of the fiber

What is tension?

force that muscle fibers generate in order to oppose a load

What is a twitch?

the mechanical response of a muscle fiber to a single action potential

What is asynchronous motor recruitment?

the recruitment of motor units at varying times in order to delay/prevent fatigue as it gives some units time to relax while recruiting others to work

What is twitch summation?

the increase in tension of a muscle fiber when there is repetitive stimulation

• possible because the duration of the actin potential is shorter than the resulting twitch

• during this, Ca2+ is initially released, however before it can all go back to the lateral sacs, more of it is released as a result of a subsequent stimulation/action potential

What is tetanus?

a smooth, sustained contraction of maximal strength when fibers are stimulated so rapidly that it doesn’t have a chance t orelax between stimuli

• 3-4x stronger than a single twitch

• can’t go on forever, easily fatigued

Describe the length tension relationship between fibers and tension.

there is an optimal muscle length at which maximal tension is developed, if it deviates from this then it would result in less tension

• in reality, for skeletal muscles, fibers aren’t too short or too long because the attachment of muscles to bones limits the shortening and lengthening of it from the optimal

In general, why is ATP important for muscular activity?

ATP provides the sole energy source for muscular activity such as power stroke and the active transport of Ca2+

What three metabolic sources is ATP derived from?

1) creatine phosphate

2) oxidative phosphorylation

3) glycolysis

Explain how ATP is derived from creatine phosphate.

creatine phosphate provides high energy Pi to add onto ADP to make ATP

• typically gives up ATP for our first minute of exercise

• during rest ATP generated by glycolysis and oxidative phosphorylation is converted into creatine phosphate that is stored by muscle cells as an energy reserve just because it’s an easy source/way to make ATP

Explain how ATP is derived from oxidative phosphorylation.

glucose and fatty acids are aerobically metabolized in the mitochondria with the use of an electron transport chain

• makes the most net ATP (32-34 ATP) however is slow, hence why is used during endurance type exercise

• make use of myoglobin (stores of oxygen) when we don’t take in enough oxygen

Explain how ATP is derived from glycolysis.

aerobic metabolism of glucose → pyruvate → lactose where it is removed through the blood

• makes 2 net ATP

• done when oxidative phosphorylation can’t keep up fast enough for energy demand

• supports high intensity exercise

What is fatigue?

the inability to maintain muscle tension because of muscle fatigue and neuromuscular fatigue

What is muscle fatigue?

occurs when an exercising muscle can no longer respond to stimulation with the same degree of contractile activity

What are two factors that cause muscle fatigue?

1) depletion of glycogen reserves (cannot make ATP via glycolysis or oxidative phosphorylation)

2) local increase in Pi from ATP breakdown (we have high Pi when we are tired)

basically use of ATP and inability to replenish that use

How does one recover from muscle fatigue?

replenishment of muscle glycogen and creatine phosphate after intense activity

What is neuromuscular fatigue?

inability of the neuromuscular junction to synthesize ACh rapidly enough to sustain chemical transmission of action potentials from the motor axon to the muscle cell

What is central fatigue?

occurs when the central nervous system no longer adequately activates motor neurons as a result of overuse

What is excess post-exercise oxygen consumption (EPOC)?

need for elevated O2 uptake during recovery from exercise

What are the three different types of skeletal muscle fibers?

1) slow oxidative (Type I)

2) fast oxidative (Type IIa)

3) fast glycolytic (Type IIb)

What is a slow oxidative (Type I) fiber?

fiber that is specialized in slow contraction

• relies on oxidative phosphorylation for ATP

• since it relies on oxidative phosphorylation it contains high numbers of mitochondria, blood supply, and myoglobin (O2 reserves)

• high resistance to fatigue

What is a fast oxidative (Type IIa) fiber?

fiber that is specialized in fast contraction and relies on oxidative phosphorylation for ATP

• high in mitochondria, blood supply, and myoglobin

• intermediate resistance to fatigue

What is a fast glycolytic (Type IIb) fiber?

fiber that is specialized in very fast contraction and relies on glycolysis for ATP

• low in mitochondria, blood supply, and myoglobin

• high in glycogen and need lots of it because glycolysis doesn’t give much ATP so have to continuously run glycolysis to make a sufficient amount of energy

• low resistance to fatigue

What are smooth muscles?

unstriated muscle fibers that are located in the walls of hollow organs and tubes such as blood vessels and the intestine

• have dense bodies holding thick and thin filaments in place, however mostly thin

What are some characteristics of the structure of smooth muscle?

• cell is spindle shaped

• less developed sarcoplasmic reticulum

• much smaller than skeletal muscle fibers

• have a single nucleus and the ability to divide

• don’t have troponin however still have tropomyosin actin and myosin

  • instead of troponin they use carmodulin

• mechanisms occurs with sliding filament however still differs from skeletal muscles

• no sarcomeres or myofibrils

• surround hollow structures and organ

Explain the steps involved in the activation of smooth muscle contraction by Ca2+.

1) neuronal/self excitation leads to Ca2+ entry from the extracellular space through channels

2) entry of extracellular Ca2+ triggers the internal release of more Ca2+ from the poorly developed SR

3) four Ca2+ binds to calmodulin and together this complex activates the myosin light chain kinase

4) activated myosin light chain kinase phosphorylates myosin on the two light chains

5) phosphorylated myosin binds to actin, activating cross bridges

6) when Ca2+ concentration is low it causes myosin light chain phosphatase to dephosphorylate myosin so that cross bridges can be halted

contraction strength is graded in proportion to the cytosolic Ca2+ concentration (diff from skeletal muscle)

What are the two different types of smooth muscles based off of how they becomes excited?

1) single unit smooth muscle

2) multi-unit smooth muscle

What is single unit smooth muscle?

smooth muscle capable of generating pacemaker activity that are coupled into a functional syncytium by gap junctions

• examples: walls of digestive tract, reproductive tract, urinary tract, and small blood vessels

What is multi-unit smooth muscle?

cells that are activated by neural input (neurogenic) and are activated separately rather than as a single unit. they respond to stimuli independently and tehy contain few gap junctions

• examples: walls of large blood vessels, large airways to the lungs, muscle of the eye that adjust the lens, iris of the ey, base of hair follicles

What are two forms of spontaneous electrical activity with smooth muscle?

1) pacemaker potential

2) slow wave potential

What is pacemaker potential of smooth muscle?

gradual depolarization until the threshold is reached (similar to cardiac muscle) and once the threshold is reach an action potential is propagated

What is slow wave potential of smooth muscle?

alternating depolarizing and hyperpolarizing swings in membrane potential below the threshold, in a way it is to prepare/being ready to create action potentials

Is there motor recruitment in smooth muscles?

no, they are already all connected by gap junctions

How is smooth muscle influenced by nerve fibers?

although neural input does not directly initiate contraction, it can modify the rate and strength of contraction

What are some characteristics associated with cardiac muscle?

• striated

• contain an abundance of mitochondria and myoglobin

• T-tubules and sarcoplasmic reticulum

• like smooth muscle, they use the Ca2+ induced Ca2+ released mechanism

• display pacemaker activity

• connected by gap junctions

• innervated by autonomic neuronal fibers (involuntary control)

• actions potentials are longer in duration than both smooth and skeletal muscle to prevent fatigue