Topic 10 - Skeletal Muscle Physiology

What are the characteristics of muscle? (4)

• excitable

• contractile

• extensible

• elastic

How is muscle excitable?

• responds to stimuli by producing APs

How is muscle contractile?

• can shorten, thicken

How is muscle extensible?

• stretches when pulled

How is muscle elastic?

• returns to original shape after contraction or extension

What the the functions of muscle? (4)

• movement

• posture, facial expression

• heat production

• protection of viscera

What is a neuromuscular junction?

• synapse where motor neurons communicate with skeletal muscle fibers to initiate contraction

How many neurons innervate a muscle fiber?

• one

How many muscle fibers can one motor neuron innervate?

• up to 150 within the same whole muscle

  • the axon of one motor neuron branches + innervates several muscle fibers

What is a motor unit?

• a single motor neuron + all the muscle fibers it innervates

What is the structure of a neuromuscular junction? (3)

• a presynaptic cell (neuron) with axon terminal filled with ACht vesicles

• postsynaptic cell (muscle) membrane (sarcolemma) - motor end plate with many receptors for acetylcholine

• pre + post-synaptic membranes are separated by synaptic cleft

What is the motor end plate of a muscle cell?

• specialized region of the sarcolemma of a muscle fiber

What is the mechanism for stimulating a skeletal muscle fiber? (7)

• AP reaches axon terminal + synaptic end bulb of neuron

• Voltage gated Ca channels open

• Ca enters the cell (neuron) = exocytosis of Ach

• Ach binds to ACh receptors on motor end plate

• Chemically gated channels open + Na → skeletal muscle fiber = end plate potential (depolarizing graded potential)

• EPP = opening of voltage-gated channels on adjacent areas of sarcolemma = AP on sarcolemma

• AP propagates along sarcolemma + down T-Tubules

What are the APs + GPs used in muscle fibre stimulation? (3)

• 1 AP on neuron → 1 EPP → 1 AP on sarcolemma

Why is there always a critical stimulus in skeletal muscle fibre stimulation? (2.1)

• lots of Ach is released at the neuromuscular junction

• the motor end plate has many receptors for Ach

  • = to inhibit the contraction of a skeletal muscle, the motor neuron needs to be inhibited

What is the sliding filament theory?

• skeletal muscle contraction controlled by the interaction of actin + myosin within sarcomeres

What is the sliding filament theory powered + regulated by? (2)

• powered by ATP

• regulated by calcium

How does calcium regulate sliding filament theory?

• binds to regulatory protein troponin

  • changes position/shape of regulatory protein tropomyosin that allows myosin to bind to actin + generate force

What is the function of troponin?

• regulates contraction by binding calcium ions = triggers a conformational change moving tropomyosin away from actin binding sites

What is the function of tropomyosin?

• allows myosin to bind to actin + generate force (when triggered by calcium driven signals)

What occurs in a relaxed muscle?

• tropomyosin covers myosin binding sites on the actin

• myosin head is activated

How are myosin heads activated?

• ATP (on myosin head) → ADP + Pi = activated + energy (stored in myosin head)

What occurs when the binding sites on actin are exposed?

• myosin binds

What are the events in skeletal muscle contraction?

• excitation of muscle fiber (electrical event)

• excitation-contraction coupling (electrical to mechanical event)

• contraction (mechanical) = sliding filament mechanism

What are the steps in the excitation of a muscle fiber? (2)

• sarcolemma is depolarized - EPP triggers an AP

• AP propagates down T-tubules to deep within fiber

What is the function of excitation-contraction coupling?

• converts the electrical event of the AP → mechanical event of contraction of the muscle fiber

What are the steps in the excitation-contraction coupling of a muscle fiber? (3)

• AP in T-tubules causes release of Ca from terminal cisternae to sarcoplasmic reticulum via mechanically gated channels

• Ca binds to troponin

• troponin-tropomyosin complex moves - exposes myosin binding sites on actin

What are the steps in the contraction (mechanical) = sliding filament mechanism of a muscle fiber? (5.1)

• activated myosin heads attach to binding sites on actin (cross bridge formation)

• energy stored in myosin heads are released - myosin head pivots (power stroke) = ADP + Pi are released + actin slides over myosin towards the center of sarcomere (M line)

• ATP attaches to myosin head = release from actin + unpivots = recovery stroke

• myosin head reactivates (ATP → ADP + Pi)

• if Ca in cytosol is high = steps repeat

  • cycle repeats many times to shorten the sarcomere

What is a power stroke?

• energy stores in myosin head is released + myosin head pivots = ADP + Pi are released

What is a recovery stroke?

• ATP attaches to myosin head = release from actin + unpivots

What is the sliding filament mechanism in a sarcomere? (1.2 + 2)

• sarcomeres shorten

  • H zone, I band shorten

  • A band = same length

• myofibrils shorten = muscle shortens

• thin (actin) + thick (myosin) myofilaments - stay same length

What are the steps in muscle fiber relaxation? (4)

• ACh is broken down by AChE on motor end plate

• sarcoplasmic reticulum actively takes up Ca (using Ca-ATPase pump)

• ATP binds to + releases myosin heads

• tropomyosin moves back to cover myosin binding sites on actin

How is Ach broken down by AChE in muscle fibre relaxation?

• Ach → acetic acid (Krebs Cycle as Acetyl CoA) + choline (recycled)

What is ATP necessary for in muscle fiber relaxation?

• cross bridge release (ATP not broken down)

• activation of myosin (ATP → ADP + Pi)

• pump Ca → sarcoplasmic reticulum

• fiber Na/K-ATPase activity

What is botulism?

• rare but fatal disease caused by nerve toxin produced by clostridium botulinum bacteria

What does botulism prevent?

• exocytosis of ACh - flaccid paralysis

How is clostridium botulinum used in a medical setting?

• treat uncontrolled blinking + crossed eyes

How is clostridium botulinum used in a cosmetic setting?

• botox - used for wrinkles, sweating

What is rigor mortis?

• stiffness after death

Why does rigor mortis occur?

• myosin heads are still activated even after death = can bind to actin

Why does ATP production gradually stop after death?

• no O2

What is the process of rigor mortis? (2)

• intracellular Ca enters from ECF + sarcoplasmic reticulum (leakage)

  • exposes binding sites on actin (cross bridges form)

• myosin heads can’t be released from actin - no new ATP is produced = muscle remains contracted

How long does rigor mortis occur for?

• starts 3 hours after death, max 12 hours

  • gradually subsides over days as cells break down

What is myasthenia gravis as an autoimmune disease?

• decreased numbers of ACh receptors = flaccid paralysis

How is myasthenia gravis treated?

• acetylcholinesterase inhibitors - promotes ACh binding to remaining receptors

What is curare poisoning?

• prevents ACh from binding to receptors = flaccid paralysis

How was curare poisoning used historically?

• in surgery - prevented people from moving during procedure

How does nicotine result in muscle spasms?

• binds to receptors and mimics ACh effect

How does black widow spider venom work?

• triggers massive release of ACh

  • could stop breathing by having muscles continuously contracted

What is muscle tension?

• force exerted by a msucle of muscle fiber

How is muscle tension determined?

• by the number of cross bridges formed

What is a cross bridge?

• myosin heads binding to actin filaments , pulling them to contract muscle fibers

What is muscle tension affected by in a fiber? (2)

• frequency of stimulation

• fiber length

What does a single stimulus produce?

• a twitch - a weak contraction + relaxation not normally occurring in skeletal muscles

What happens after a single stimulus? (4)

• 1 stimulus = 1 AP

• latent period

• contraction period

• relaxation

What occurs in the latent period?

• processes associated with excitation and excitation-contraction coupling occur

What occurs in the contraction period? (1.3.1)

• increase in tension

  • cross bridge formation + sliding filaments

  • lots of Ca released from sarcoplasmic reticulum on stimulation

  • a LOt of Ca released from sarcoplasmic reticulum on stimulation - BUT rapidly taken back by sarcoplasmic reticulum Ca-ATPase

    • = not all myosin heads attach + muscle doesn’t reach max. possible tension

What occurs in relaxation?

• decrease in tension

  • Ca pumped into SR ; ATP releases myosin; etc

What is temporal summation?

• the 2nd stimulus arrives before complete relaxation from the 1st

What occurs in temporal summation? (2)

• muscle AP is always completed (refractory period)

• uptake of Ca is not yet complete (fiber relaxing)

What does the 2nd stimulus in temporal summation cause?

• the release of more Ca adding to the Ca already in cytosol = more myosin heads can attach

What is wave summation?

• a 2nd contraction with higher tension in temporal summation

What occurs in the rapid sequence of stimuli?

• tension increases further (increased Ca availability = wave summation)

What does a rapid sequence of stimuli result in?

• incomplete/unfused tetanus

What is incomplete/unfused tetanus?

• partial relaxation between contractions = quivering

What does a high frequency of stimuli result in?

• complete/fused tetanus

What is complete/fused tetanus?

• no relaxation between contractions

What occurs to troponin when there’s a high frequency of stimuli?

• all troponin is saturated with Ca + the fiber is warm

Why is the muscle fiber warm when there’s high frequency of stimuli?

• ATP synthesis produces heat = works faster

What length of fiber is optimum for muscle tension?

• resting length

Why is resting length optimum for a fiber?

• allows for max number of cross bridges formed upon stimulation = max tension

Why does tension decrease in a shorter fiber?

• thin filaments overlap + interfere with cross bridge formation = fewer cross bridges form = decrease in tension

  • minimum length - 70% optimal

Why does tension decrease in a longer fiber?

• not all myosin heads are near actin binding sites = fewer cross bridges form = decrease in tension

  • max length - 130% optimal

How does a thicker fiber affect muscle tension?

• thicker = more myofibrils/fiber = more tension

How can fiber thickness increase? (2)

• exercise

• testosterone

How does fatigue affect muscle tension? (2)

• muscle doesn’t contract well

• reduced max tension

What are the characteristics of a fast muscle fiber? (2)

• contracts/relaxes rapidly

• white (little myoglobin)

What are the characteristics of a slow muscle fiber? (2)

• contracts/relaxes slowly

• red (more myoglobin)

How does the number of fibers contracting affect muscle tension? (1.2 + 1)

• more active motor units = more tension

  • small motor units recruited first

  • larger ones added when more tension is needed

• 1 neuron innervating 10 fibers is weaker vs 1 neuron innervating 1000 fibers

How does muscle size affect muscle tension?

• larger muscle = more fibers = more myofibrils

What is muscle tone?

• low level of tension in a few fibers - develops as different groups of motor units are alternately stimulated over time

  • gives firmness to muscle

What are the characteristics of isotonic muscle contraction? (3)

• muscle changes length

• tension exceeds the resistance of the load lifted

• uses ATP

What are the characteristics of isometric muscle contraction? (4)

• muscle length is constant

• tension is less than required to move length

• tension increases - cross bridges form but no shortening

• uses ATP

What muscle contractions are used in the biceps brachii when lifting a book? (2)

• isotonic - lift

• isometric - hold

What occurs during resting conditions? (2.2)

• fatty acids used to produce ATP (aerobic)

• storage of:

  • glycogen

  • creatine phosphate (C-P)

How is creatine phosphate produced?

• ATP + creatine = ADP + C-P

What type of exercise is short term exercise?

• anaerobic (without oxygen)

What does short term exercise use? (3.1)

• available ATP

• uses creatine phosphate to produce ATP (lasts ~15 secs)

  • C-P + ADP = ATP + creatine

• muscle glycogen → glucose → pyruvic acid → anaerobic pathway → lactic acid (lasts ~30 secs-2 mins)

What type of respiration does long term exercise use?

• aerobic

What does long term exercise use? (3)

• ATP from aerobic pathway

• glucose from liver

• fatty acids - used more as exercise continues

What O2 sources are used in long term exercise? (2)

• blood hemoglobin

• muscle myoglobin

What is physiological fatigue? (2)

• inability to maintain tension

  • fatigue reduces ATP use = protective

What is physiological fatigue due to? (3.2)

• depletion of energy supplies

• build up of end products:

  • H+ from lactic acid

  • Pi from (ATP → ADP + Pi)

• failure of APs

How does a build up of lactic acid = fatigue?

• H+ from lactic acid - muscle contraction compresses blood vessels = decrease of O2 to muscle = anaerobic for periods, even in long term exercise

How does a build up of Pi = physiological fatigue? (1.1)

• Pi binds to Ca = less Ca binding to troponin

  • slows release of Pi from the myosin = slows cross bridge release from actin

How do the failure of APs = physiological fatigue? (1.1)

• increase in potassium in small space of T-tubules during rapid stimuli disturbs membrane potential + stops Ca release from sarcoplasmic reticulum

  • long term - neuron runs out of ACh

What is psychological fatigue due to? (2)

• failure of CNS to send commands to muscles

• due to “the burn”/”the wall”

What is EPOC? (1.1)

• excess post-exercise O2 consumption

  • recovery O2 consumption (deep rapid breathing)

What is O2 used for in EPOC? (3.2)

• replenish stores of glycogen, creatine, phosphate, O2 on Hb/myoglobin

• converts lactic acid to

  • - pyruvic acid → Krebs

  • glucose in liver

• increased body temp from exercise = increased O2 demand