Chapter 9: Muscle

Question 1

9.1 Structure

Answer 1

allosteric shift to get troponin off of the tropomyosin

Excitation- Contraction

a. cross-bridge formation
b. the power (working) stroke
- adp and p are released

c. cross bridge detachmenr
- after atp attaches to myosin, the link between myosin and actin weakens
- the myosin hed detaches
d. cocking of the myosin head
- a

BE ABLE TO DRAW AND EXPLAIN THE THE CROSS BRIDGE CYCLE

8. THE SARCOplasmic reticulum

• signal from sarcolima
• t tubule in between each sr
• well of calcium
• integral proteins on the t-tubule and the sr
• dihydropiyridine receptor
• cell at rest: bird beak not in flower
• cell the calcium comes out between the leaves of the petals
• dhp is on the sarcolima, ryanodine is on the sr
• slow chart–> fil out with ifromsstion later

KNOW THE AFFECT OF CA2+ IN NEURON AND MUSCLE

Question 2

9.2 Molecular Mechanisms of Skeletal Muscle Contraction

Question 3

9.3 Mechanisms of Single Fiber Contraction

Answer 3

1. Mechanics of Single-Fiber Contraction

• a muscle fiber generates a force called tension
• tension opposes the load
• TWITCH- mechanical response of a muscle fiber to a single AP
  a. only in lab setting
• can pull two things toward each other and produce work
• tension necessary to do work

2. Muscle Twitch

• motor unit’s response to single action potential of its motor neuron
• simplest contraction observable in lab (recorded as MYOGRAM)
• muscle contract faster than it relaxes
  1. LATENT PERIOD
     
     • E-C coupling
     • no muscle tension
     • from the onset of the stimulus to when we see observable stimulus
  2. PERIOD OF CONTRACTION
     
     • cross-bridge formation
     • tension increases
     • Ca2+ leaves sarcoplasmic reticulum
       
       3. PERIOD OF RELAXATION
     • Ca2+ reentry into SR
     • tension declines to zero
     • must remove almost all Ca2+ to get the tension to resting value
• muscles differ in phases
• differ in fast vs. slow-twitch fiber
• some muscles work faster than others

3. Isotonic vs. Isometric Contractions
   A. Isotonic
   - muscle changes in length and moves load
   - thin filaments slide
   - CONCENTRIC CONTRACTION: muscle shortens and does work
   - ECCENTRIC CONTRACTIONS: muscle generates force as it lengthensB. Isometric
   - load greater than tension muscle can develop
   - tension increases to muscle’s capacity, but the
   muscle neither shortens nor lengthens
   a. cross-bridges generate force but do not move actin filaments
   - making cross-bridges but don’t slide on a cellular level
   C. Influence of Load
   - muscles contract fastest when no load is added
   - ↑ load = ↑ latent period, ↓ velocity of shortening, ↓ duration twitch, ↓ distance
4. Graded Muscle Response
   - Graded muscle responses
   a. varying strength of contraction for different demands
   - required for proper control of skeletal movementA. Frequency-Tension
   - muscle twitch= single contraction from a single stimulus
   - SUMMATION
   a. increases stimulus frequency → second contraction of greater force
   b. muscle does not completely relax between stimuli
   c. additional Ca2+ release with second stimulus stimulates more tension
   - further increase in stimulus frequency → UNFUSED TETANUS

- ↑ Ca2+ → ↑ x-bridges → ↑ force
** greater frequency action potentials → greater contractions!!!**

• if stimuli are given quickly enough, muscle reaches maximal tension –> fused tetanus
  a. smooth, sustained contraction
• FUSED TETANUS
  a. too long
  b. no muscle relaxation → muscle fatigue
  c. muscle cannot contract = zero tension
  B. Length-Tension
• passive tension due to titin proteins
• active tension during tetanic stimulation
• actively stimulating produces a ton of force
• OPTIMAL LENGTH - L0
  a. the greatest number of cross-bridges when muscle fibers are around 100% of normal resting length
  b. most force
  c. developed due to evolution
• too short
  a. actin fibers block other actin binding sites at <80% normal resting length
  b. Z discs hit myosin
  c. less force
  d. <60%, no force
• too long
  a. actin fibers pulled off myosin at >120% normal resting length
  b. less force
  c. >175% - no force

GOLDILOCKS → JUST RIGHT!!!!! longer or too short = loose force, optimal length is optimal because there is 100% cross-bridging

5. Muscle Metabolism: Energy for Contraction
   - ATP only source used directly for contractile activities
   
   1. move and detach cross-bridges
   2. calcium pumps in SR
   3. return of Na+ & K+ after excitation-contraction coupling

• available sotres of ATP depleted in 4-6 seconds
• ATP regenerated by:
  A. Direct Phosphorylation of ADP by CREATINE PHOSPHATE (CP)
• CP + ADP → C + ATP
• creatine kinase
• reversible
  at rest- CP 5x > ATP
• short burst of ATP allows other sources to catch upB. Aerobic Respiration
• produces 95% of ATP during rest and light to moderate exercise
• slow
• efficient
• series of chemical reactions that require oxygen
• occur in mitochondria
• breaks glucose into CO2, H2O, and large amount of ATP
• fuels (in order of use)
  
  1. stored glycogen
  2. blood-borne glucose
  3. free fatty acids

ATP SYNTHASE → takes ADP and adds a phosphate group to make ATP; oxidative phosphorylation; pumping H+ ions across membrane makes chemiosmotic membrane that helps generate energy; MEMORIZE THIS

 C. Anaerobic Respiration - glycolysis- 
 a. does not require oxygen 
 b. used when ATP breakdown > 70%
 c. glucose degraded to 2 pyruvic acid molecules (normally enter mitochondria → aerobic respiration)  - at 70% of maximum contractile activity 
 a. bulging muscles compress blood vessels; oxygen delivery is impaired 
 b. pyruvic acid converted to lactic acids - lactic acid 
 a. diffuses into the bloodstream 
 b. used as fuel by liver, kidneys, and heart
 c. converted back into pyruvic acid or glucose by liver 
 d. decreases local pH (→pain and decreases enzyme function at high levels) 
 e. yields only 5% as much ATP as aerobic respiration
 f. but produces ATP 2.5 times faster (adds about 40 extra seconds of muscle power)

 D. Oxygen Debt - oxygen deficit created during exercise must be replenished afterward = OXYGEN DEBT  - increasing oxygen consumption - to return the muscle to resting state:
 1. oxygen reserves replenished 
 2. lactic acid converted to pyruvic acid 
 3. ATP and creatine phosphate reserves replenished 
 4. glycogen stores replaced 

6. Muscle Fatigue
   - physiological inability to contract despite continued stimulation
   - decreased shortening velocity
   - slower relaxation rate
   - acute metabolic changes
   a. decrease in ATP
   b. increase in ADP, P, MG2+, H+ (from lactic acid), & oxygen free radicals
   - consequences
   
   1. ↓ rate of Ca2+ release, reuptake, & storage by SR
   2. ↓ ability of CA2+ activate thin filament proteins
   3. inhibit binding & power-stroke of myosin X-bridges
      
      • long-term fatigue
        a. ryanodine Ca2+ channels become leaky
        b. activate proteases that break down contractile proteins
        c. depletion of glycogen
        d. low blood glucose
        e. dehydration
      • CENTRAL COMMAND FATIGUE
        a. CNS stops sending APs to motor neurons
        b. No AP in motor neuron = no AP in muscle cell
        c. no contraction even though muscle is not truly fatigued
7. Muscle Fiber Type
   - classified in two ways
   
   1. speed of contraction - SLOW OR FAST FIBERS according to:
      a. speed at which myosin ATPases split ATP
      b. pattern of electrical activity of motor neurons
   2. metabolic pathways for ATP synthesis
      a. OXIDATIVE FIBERS- use aerobic pathways
      b. GLYCOLYTIC FIBERS - use anaerobic glycolysis
      
      • three types:
   3. SLOW OXIDATIVE FIBERS
      a. smaller diameter, darker color due to myoglobin, fatigue-resistant, is aerobic, has steady power, has endurance
      b. fatigue very slowly
   4. FAST OXIDATIVE FIBERS
      a. start to fatigue after 10-15 minutes
   5. FAST GLYCOLYTIC FIBERS
      a. large diameter, pale color, easily fatigued, is anaerobic, has explosive power, fatigues easily
      b. fatigue rapidly
      c. 1-2 minutes
      
      • most muscles contain a mixture of fiber types
        a. all fibers in one motor unit
        b. have a range of contractile speeds & fatigue resistance
        c. genetics dictate individuals percentage of each

predominance of fast glycolytic (fatigable) fibers
↓
↑ contractile velocity

small load
↓
↑ contractile velocity & ↑ contractile duration

the predominance of slow oxidative (fatigue-resistance) fibers
↓
↑ contractile duration

Question 4

9.6-9.7

Answer 4

1. Muscle Tone
   - constant, slightly contracted state of all muscles
   - due to spinal reflexes
   a. groups of motor units alternately activated in response in input from stretch receptors in muscles
   - keeps muscles firm, healthy, and ready to respond
2. Motor Unit Recruitment
   - RECRUITMENT (multiple motor unit summation)
   a. controls force of contraction
   - SUBTHRESHOLD STIMULI
   a. no observable contractions
   - THRESHOLD STIMULI
   a. stimulus strength causing first observable muscle contraction
   - MAXIMAL STIMULUS
   a. strongest stimulus that increases contractile force
   - muscle contracts more vigorously as stimulus strength increases above threshold
   - contraction force precisely controlled by recruitment
   a. activated more and more muscle fibers
3. Size Principle
   - recruitment works on SIZE PRINCIPLE
   a. motor units with larger and larger fibers recruited as stimulus intensity increases
   b. largest motor units activated only for most powerful contractions
   c. beyond maximal stimulus → no increase in force of contraction
   d. small fibers (motor units 1) for less force, medium fibers (motor unit 2) for medium force, large fibers (motor unit 3) for large force
4. Muscle Fiber Type & Recruitment
   - slow oxidative fibers are first stimulated to contract
   a. provide basal muscle tension (tone)
   - more recruitment = faster contraction and ↑ duration of contraction
5. Force of Whole Muscle Contraction
   - force of contractions depends on NUMBER OF CROSS BRIDGES ATTACHED
   - affected by:
   
   1. number of muscle fibers stimulated
      a. recruitment
   2. relative size of fibers
      b. hypertrophy of cells increases strength
   3. frequency of stimulation
   4. degree of muscle stretch
      
      • as more muscle fibers are recruited (as more are stimulated) ↑ force
      • relative size of fibers
        a. bulkier muscles & hypertrophy of cells ↑ force
      • frequency of stimulation
        a. ↑frequency = more cross bridges = ↑ force
      • muscle and sarcomere stretched to slightly over 100% of resting length = ↑ force
      • combination of all 4 produces the more force
6. Control of Shortening Velocity
   - shortening velocity of a whole muscle depends upon
   
   1. load
   2. motor unit type
   3. number of motor units recruited
7. Homeostatic Imbalance
   - disuse atrophy
   a. result of immobilization
   b. muscle strength declines 5% per day
   - denervation atrophy
   a. without neural stimulation muscles atrophy to 25% initial size
   b. fibrous connective tissue replaces lost muscle tissue, rehabilitation impossible
8. Adaptations to Exercise
   - resistance exercise (typically anaerobic) results in
   a. muscle hypertrophy
   due primarily to increase in fiber size
   more myofibrils → more x-bridges → more strength
   - increases in:
   a. mitchondria
   b. myofilaments
   c. glycogen stores
   d. connective tissue

• endurance (aerobic) exercise
  a. leads to increased
  b. muscle capillaries
  c. number of mitochondria
  d. myoglobin synthesis
• results in greater endurance, strength, and resistance to fatigue
• may convert fast glycolytic fibers into fast oxidative fibers

9. Skeletal Muscle Disorders
   - many disorders caused by defects in NS vs. muscle fibers
   - poliomyelitis
   a. viral disease that destroys motor neurons
   b. paralysis of skeletal muscle
   c. death due to respiratory failure
   - muscle cramps
   a. involuntary tetanic contraction
   b. action potentials fire at abnormally high rates
   c. hypotheses: electrolyte imbalances in the extracellular fluid (ECF) surrounding both the muscle and nerve fibers
   d. chemical imbalances stimulating sensory receptors that activate reflexive contraction
   - hypocalcemic tetany
   a. involuntary tetanic contraction- CA2+ at high concentrations will block Na+ voltage, but without the Ca2+, the threshold is lowered, so it does not require a lot to require threshold and all action potential is immediately depolarizing the membrane and causing an action
   b. extracellular Ca2+ concentration <40% normal
   c. low extracellular Ca2+ (hypocalcemia) → less +++ ECF → more Na+ channels open in sarcolemma → depolarization → spontaneous action potentials
   d. chvostek’s sign and trousseau’s sign show involuntary intense tetanic contraction
   - muscular dystrophy
   a. affects one in every 3,500 males (fewer females)
   b. progressive degeneration of skeletal and cardiac muscle fibers
   c. death from respiratory or cardiac failure
   d. absence or defect in costameres in striated muscle- link the Z discs of the outermost myofibrils to the sarcolemma and extracellular matrix
   - myasthenia gravis
   a. affects about one out of every 7,500 Americans- occurs more in women
   b. autoimmune
   c. destruction of nicotinic ACh receptor proteins of the motor end plate
   d. treatments- acetylcholinesterase inhibitors (e.g., neostygmine), glucocorticoids suppress immune function, plasmapheresis removes antibodies

Question 5

9.8-9.10

Answer 5

1. Overview of Three Muscle Types
   - muscle tissue
   a. all contractile tissues
   - three types:
   
   1. cardiac
   2. skeletal
   3. smooth
2. Smooth Muscle
   - found in walls of most hollow organs (except heart)
   - usually in two layers (longitudinal and circular)
   - spindle-shaped
   - single nucleus
   - mitotic
   - smaller than skeletal muscle fibers
   - contractile elements are not in straight lines
   - has mesh-like networks of filaments
   - have:
   a. thick myosin-containing
   d. thin actin-containing filaments
   c. tropomyosin
   d. NO TROPONIN
   - no m-line or z-discs, instead, have dense bodies
   - the thin filaments are anchored either to the plasma membrane or to DENSE BODIES
   - the thick and thin filaments are not organized into myofibrils
   - there are NO sarcomeres
   a. NO banding pattern
   - contraction occurs by a sliding-filament mechanism
   - hollow structures/organs undergo volume changes during smooth muscle contraction
   - have similar length-tension relationship as skeletal muscle
   a. can create tension over wider range of lengths
3. Smooth Muscle Contraction

CROSS-BRIDGE ACTIVATION
1. calcium binds to CALMODULIN
2. calcium-calmodulin binds to MYOSIN LIGHT CHAIN KINASE (MLCK), activating it
3. Active MLCK USES atp to phosphorylate myosin head
4. phosphorylation → forces x-bridge toward thin filament
5. cross-bridge cycling

RELAXATION
myosin must be dephosphorylated → unable to bind to actin
- dephosphorylation is mediated by the enzyme MYOSIN LIGHT-CHAIN PHOSPHATASE (MLCP)
- two sources of Ca2+
1. the sarcoplasmic reticulum
2. extracellular Ca2+ from voltage & ligand-gated Ca2+ channels
- to relax, the Ca2+ has to be removed either to the SR or back to the extracellular fluid

4. Smooth vs. Skeletal Muscle Contraction
   - both use calcium to activate contraction
   - skeletal: calcium exposes the binding site on actin
   - smooth: calcium-calmodulin → activates MLCK → activates myosin head
5. Smooth Muscle Membrane Activation
   - smooth muscle responses can be graded
   a. more cytosolic calcium → bigger responses
   - input to smooth muscle can be either excitatory or inhibitory
   a. excitatory → more calcium channels open
   b. inhibitory → fewer calcium channels open
   - spontaneous electrical activity
   a. spontaneous depolarization to threshold- PACEMAKER POTENTIAL
   b. other smooth muscle pacemaker cells → SLOW WAVES- stimulus depolarizes above threshold ↑ APs
   c. gut - a lot of pacemaker cells- smooth muscle tends to contract rhythmically even in the absence of neural input
   - innervation of smooth muscle a.neurotransmitters released by autonomic neuron endings
   b. swollen regions known as VARICOSITIES -
   1. contain vesicles with neurotransmitter
   2. some are released when AP passes through
   
   3. no motor end plate
      c. varicosities from a single axon may be located along several muscle cells
      d. a single muscle cell may be located near varicosities of SNS and PNS axons
      e. SINGLE-UNIT SMOOTH MUSCLES
      1. respond to stimuli as a single unit
      2. cells are connected by GAP JUNCTIONS
      3. ex: intestines, uterus, small-diameter blood vessels
      f. MULTI-UNIT SMOOTH MUSCLES
      1. contain cells that respond to stimuli independently
      2. contain few gap junctions
      3. ex: large airways, large arteries, attached to hair bulbs
      
      • local factors
        a. local factors can also alter smooth muscle tension
   4. paracrine signals (nitric oxide, NO)
   5. acidity
   6. O2 and CO2 levels
   7. osmolarity
   8. ion composition of ECF
      b. alter smooth muscle contraction in response to changes in the muscle’s immediate internal environment
      c. some streched by contracting when they are stretched
      d. stretching opens mechanosensitive ion channels leading to membrane depolarization
      
      • the resulting contraction opposes the forces acting to stretch the muscle
6. Cardiac Muscle
   - use the sliding filament mechanism to contract
   -striated
   - 1-2 central nuceli
   - INTERCALATED DISCS with desmosomes of gap junctions
   - INTERCALATED DISCS with desmosomes and gap junction
   - AUTORHYTHMICITY
   - the absolute refractory period is about 250 ms
   a. prevents tetanic contractions in the heart
7. Excitation-Contraction Coupling in Cardiac Muscle
8. the membrane is depolarized by Na+ entry as an action potential begins
9. depolarization opens L-type Ca2+ channels in the T-tubules
10. a small amount of “trigger” Ca2+ enters the cytosol, contributing to cell depolarization. that trigger Ca2+ binds to and opens, ryanodine receptor Ca2+ channels in the sarcoplasmic reticulum membrane
11. Ca2+ flows into the cytosol, raising the Ca2+ concentration
12. binding of Ca2+ to troponin exposes cross-bridge binding sites on thin filaments
13. cross-bridge cycling causes force generation and sliding of thick and thin filaments
14. Ca2+ ATPase pumps return Ca2+ to the sarcoplasmic reticulum
15. Ca2+ATPase pumps (and also Na2+/Ca2_ exchangers; not shown) remove Ca2+ from the cell
16. the membrane is repolarizes when K+ exits to end the action potential
17. Cardiac vs. Skeletal Muscle Twitch
18. Comparison of Skeletal, Cardiac, and Smooth Muscle

BE ABLE TO EXPLAIN ALL SMOOTH MUSCLE MECHANISMS OF CONTRACTION; BE ABLE TO DO THIS FOR ALL OF THEM