Topic 10: Skeletal Muscle Physiology Flashcards
Muscle Characteristics
- excitable – respond to stimuli and produce action potentials
- contractile – can shorten, thicken
- extensible – stretch when pulled
- elastic – return to original shape after contraction or extension
Muscle Functions
- movement – e.g. walking, breathing
- posture, facial expression
- heat production ⇒ 37°C
- protection of viscera – body wall
Neuromuscular Junction
- each muscle fiber (cell) innervated by only 1 neuron
- axon of motor neuron branches to innervate several muscle fibers (1 neuron ⇒ ~150 fibers within same whole muscle)
- a single motor neuron and ALL the muscle fibers it innervates = a motor unit
Neuromuscular Junction Structure
- presynaptic cell (neuron) with ACh (nt) vesicles
- postsynaptic cell (muscle) membrane (sarcolemma) - specialized region with ACh receptors (= motor end plate)
- two membranes separated by synaptic cleft
Neuromuscular Junction Function
- AP reaches axon terminal and synaptic end bulb of neuron
- Ca2+ enters via voltage gates ⇒ causes exocytosis of Ach
- ACh binds to ACh receptors on motor end plate
- chemical gates open and Na+ enters ⇒ End Plate Potential (EPP = a depolarizing GP)
- EPP causes opening of Na+ voltage gates on adjacent sarcolemma ⇒ AP (AP has same properties/channels as on a neuron) – propagates along sarcolemma
Neuromuscular Junction Note
- 1 AP (neuron) →1 EPP → 1 AP (always!)
i. e. always a critical stimulus because: - lots of ACh released
- motor end plate has many receptors ∴ to inhibit skeletal muscle must inhibit motor neuron
In a relaxed muscle
- tropomyosin covers myosin binding sites on the actin
- the myosin head is activated
Myosin Head Activation
- ATP (on head) breaks down to ADP (on head) and energy (stored in head)
- once actin binding sites on actin are exposed, myosin binds
Excitation of muscle fiber (electrical event)
- Sarcolemma depolarized - EPP ⇒ AP
- AP propagates down T-tubules to deep within fiber
Excitation-contraction coupling (electrical to mechanical event)
- AP in T-tubules cause release of Ca2+ (coupling agent) from terminal cisternae of sarcoplasmic reticulum (SR) via mechanically gated channels
- Ca2+ binds to troponin
- Troponin-tropomyosin complex moves, exposing myosin binding sites on actin
Contraction (mechanical event) = Sliding Filament Mechanism
- Activated myosin heads attach to binding sites on actin (cross bridge formation)
- Energy stored in myosin head is released - myosin head pivots (= POWER STROKE), ADP + Pi are released. Actin slides over myosin toward center of sarcomere (M line)
- ATP attaches to myosin head, causing its release from actin + unpivot = RECOVERY STROKE
- Myosin head reactivates (ATP ⇒ ADP + Pi)
- If Ca2+ in cytosol remains high these steps repeat
- cycle repeats many times to shorten the sarcomere
Sliding Filament Mechanism – Sarcomere
Sarcomeres shorten -H zone, I band shorten -A band = same length Myofibrils shorten ∴ muscle shortens thin (actin) and thick (myosin) myofilaments remain the same length
Muscle Fiber Relaxation Steps
- ACh broken down by AChE on motor end plate (facing cleft) produces acetic acid (Krebs cycle) and choline
- SR actively takes up Ca2+ (Ca2+-ATPase)
- ATP binds to and releases myosin heads
- Tropomyosin moves back to cover myosin binding sites on actin
Muscle Fiber Relaxation ATP necessary for
- cross bridge release (ATP not broken down)
- activation of myosin (ATP ⇒ ADP + Pi)
- pump Ca2+ into SR
- fiber Na+/K+-ATPase activity
Clinical Applications
Botulism, Rigor Mortis, Myasthenia gravis, Curare Poisoning, Nicotine, Black Widow Spider Venom
Botulism
- improper canning - Clostridium botulinum
- prevents exocytosis of ACh - flaccid paralysis
- medical - treat uncontrolled blinking, crossed eyes
- cosmetic – Botox (wrinkles, sweating)
Rigor Mortis
- “stiffness of death”
- intracellular Ca++ ⇑ from ECF, SR (there is leakage) ⇒ binding sites exposed (crossbridges) ⇒ myosin heads not released from actin (no new ATP produced)
- starts ~ 3 hrs after death, max at about 12h
- gradually subsides over days as cells break down
Myasthenia gravis
- ⇓ in ACh receptors (autoimmune)
- flaccid paralysis
- treatment - AChE inhibitors (⇑ binding to remaining receptors)
Curare Poisoning
- prevents ACh from binding to receptors
- flaccid paralysis – was used in surgery
Nicotine
mimics ACh effect (binds to receptors) – get muscle spasms
Black Widow Spider Venom
triggers massive release of ACh - muscles continuously contract - stop breathing
Muscle Tension
= force exerted by a muscle or muscle fiber
-determined by number of cross bridges formed
In a fiber, affected by:
-Frequency of stimulation:
-Fiber Length
-Size of fiber
-Fatigue
Frequency of stimulation
- Single stimulus
- 2nd stim. arrives before complete relaxation from 1st
- Rapid sequence of stimuli
- High frequency of stimuli
Single stimulus
produces a twitch (a weak contraction and relaxation - not normally occurring in skeletal muscles)
- single stimulus ⇒ 1 AP (lasts 1-2 msec)
- latent period (~2 msec)
- -excitation-contraction coupling occurring
- contraction period (10-100 msec) - ⇑ tension
- -cross bridge attachment and sliding filaments
- -a lot of Ca2+ released from SR on stimulation, but taken back rapidly by SR Ca2+-ATPase, so not all myosin heads attach – does not reach maximum possible tension
- relaxation - ⇓ tension
- -Ca2+ pumped into SR; ATP releases myosin; etc
2nd stim. arrives before complete relaxation from 1st
- muscle AP always completed (refractory period) BUT uptake of Ca2+ by SR is not yet complete (fiber relaxing)
- 2nd stimulus causes release of more Ca2+, adding to that already in the cytosol ⇒ more myosin heads can attach
- produces 2nd contraction with ⇑ tension = wave summation (contraction has no refractory period)
Rapid sequence of stimuli
- tension increases further (⇑ Ca2+ availability ⇒ wave summation)
- partial relaxation between contractions produces quivering = incomplete tetanus
High frequency of stimuli
- no relaxation between contractions i.e. sustained contraction = complete tetanus
- all troponin saturated with Ca2+ and fiber warm (ATP synthesis - heat) ⇒ works faster
- occurs normally in the body
Fiber length
Resting fiber length is optimum
-allows for a maximum # of cross bridges formed upon stimulation ∴ max tension
⇓ tension if shorter or longer:
-shorter ⇒ thin filaments overlap and interfere with cross bridge attachment (min length = 70% of optimal)
-stretched ⇒ not all myosin heads near actin binding sites (max length = 130% of optimal)
Size of fiber
thickness = more myofibrils/fiber
- thicker = more tension
- ⇑ with e.g. exercise, ♂ = testosterone
Fatigue
- muscle does not contract well
- reduced maximum tension
Fiber types in a muscle differ
- Fast – contract/relax rapidly - white (little myoglobin)
- Slow – contract/relax slowly - red (more myoglobin) e.g. postural muscles
in a whole muscle, tension affected by
Number of fibers contracting: -more active motor units = ⇑ tension -small motor units recruited first, then larger ones added when more tension needed # fibers/motor unit: -more fibers/unit = ⇑ tension -1 neuron ⇒ 10 fibers (weak) vs 1000 fibers (strong) Muscle size: -larger = more fibers Fatigue
Muscle Tone
- low level of tension in a few fibers that develops as different groups of motor units are alternately stimulated over time
- gives firmness to muscle
Whole Muscle Contraction types
- Isotonic:
- Isometric
Isotonic
- muscle changes length
e. g. flexion at the elbow - tension > weight of forearm - tension (relatively constant) exceeds the resistance of the load lifted
- uses ATP
Isometric
- muscle length constant
- tension less than required to move load
- tension increases – cross bridges form but no shortening
- uses ATP
Whole Muscle Contraction example
Lift a book:
- muscle = biceps brachii
- isotonic to lift
- isometric to hold
Muscle Metabolism
energy for contraction:
- During resting conditions
- During short term exercise (i.e. < 1 minute) e.g. sprinting
- Long term exercise (1 min to hours)
During resting conditions
fatty acids used to produce ATP (aerobic) storage of: -glycogen -creatine phosphate (C~P) -ATP + Creatine ⇒ ADP + C~P
During short term exercise (i.e. < 1 minute) e.g. sprinting
primarily anaerobic
- use available ATP
- creatine phosphate used to produce ATP (lasts ~ 15 secs)
- C~P + ADP ⇒ ATP + creatine
- muscle glycogen ⇒ glucose ⇒ pyruvic acid ⇒ anaerobic pathway ⇒ lactic acid (lasts ~ 30 seconds
Long term exercise (1 min to hours)
- ATP - from aerobic pathway
- glucose (from liver)
- fatty acids - used more as exercise continues
- O2 sources: blood hemoglobin and muscle myoglobin
- but sometimes anaerobic (discussed under fatigue)
Muscle Fatigue types
- Physiological Fatigue
- Psychological Fatigue
Physiological Fatigue
-inability to maintain tension - not completely understood
-fatigue ⇓ ATP use ∴ protective (if too little, cross bridges can’t release)
Due to:
-depletion of energy supplies e.g. glycogen
-build-up of end products
-failure of APs
build-up of end products
- H+ from lactic acid - muscle contraction compresses blood vessels - ⇓O2 to muscle ∴ anaerobic for periods, even in long term exercise
- Pi (from ATP⇒ADP + Pi) binds to Ca2+
- less binds to troponin
- slows the release of the Pi from the myosin – slows cross bridge release from actin
failure of APs
- ⇑ [K+] in small space of T-tubules during rapid stimuli ⇒ disturbs MP, stops Ca2+ release from SR
- long term: neuron runs out of ACh (not usual in healthy person)
Psychological Fatigue
failure of CNS to send commands to muscles ⇒ probably due to lactic acid
Muscles and EPOC
EPOC = Excess Post-exercise O2 Consumption
-recovery O2 consumption (deep rapid breathing)
O2 used to:
-replenish stores of glycogen, C~P, O2 on Hb/myoglobin
-convert lactic acid to:
-pyruvic acid ⇒ Krebs
-to glucose in liver
also ⇑ in body temp from exercise = ⇑ O2 demand (faster chemical reactions)
