Flashcards in Lecture 31 - Muscular Dystrophies - Muscle Structure, Function and Neuromuscular Transmission Deck (47):
What are muscle disorders?
Affect one or more of the different muscle tissue type (smooth, cardiac, skeletal)
Muscles needed to move joints, thus these diseases result in motion disorder
Differentiate between myopathies and muscular dystrophies
• Genetic and acquired disorders of the muscle contractile apparatus (thick, thin filaments etc)
• Generally static pathology
• Genetic disorders of the supporting structures (DAPC)
• Progressive degeneration
• Sacrolemmal proteins
• Proteins which anchor the contractile apparatus in place
Outline these features of skeletal muscle:
Talk about the variation seen in these features
• Attached to bone
• Voluntary control
• Different contraction velocities depending on ability
• Variable metabolic processes used to generate energy
• Made up of muscle fibres (the cells)
• Variable colour depending on myoglobin content
What are striations?
Muscle fibres (cells) containing alternating light and dark bands
What is myoglobin?
Oxygen storage protein for mitochondria
Has a higher affinity for oxygen that haemoglobin → oxygen movement into muscle cells from blood favoured
Discuss the differences in skeletal and smooth muscle
• Myofibres: parallel muscle fibres grouped into bundles
• Not striated
NB both are:
Describe muscle fibres in detail
Muscle belly - Epimysium - Perimysium - Fasciculus - Endomysium - Muscle fibres (cells) - Myofibrils within cells
Fasciculi: bundles of muscle fibres
Muscle fibres: the cells
• Sarcolemma (membrane)
• Myofibrils: contractile component
What is the sarcolemma?
The membrane of muscle fibres
Compare the location of the following:
These are all cocnective tissues surrounding various structures
• Ensheaths entire muscle
• Ensheaths fasciculi
• Ensheaths individual muscle fibres
What is a sarcomere?
Describe its structure in detail
Organised subunit repeated along the length of muscle fibres
Smallest contractile portion of a muscle
• Thick (myosin) filaments, w/ globular heads: 'Cross-bridges'
• Thin (actin) filaments
• M line: central anchor of sarcomere
• A band: length of myosin filaments, + actin (Dark band)
• H zone: centre of sarcomere, myosin filaments
• Z disc: attaches actin filaments in adjacent sarcomeres
• I band: isotropic, aligned actin filaments (Light band)
• Tropomyosin: weaved around the actin filaments
Describe the sliding filament model of muscle contraction
• Tropomyosin covers myosin binding sites on actin
1. Ca2+ influx into cytoplasm and binds to troponin
2. Tropomyosin moves, revealing myosin binding sites on actin
3. Myosin heads bind to actin forming cross bridges
4. Release of ADP and Pi
5. Conformational change of myosin head: powerstroke
6. Actin pulled into the centre of the sarcomere: Z discs pulled into centre
7. ATP binds myosin head, cross-bridge breaks, myosin returns to unattached position
8. ATP hydrolysis brings about cocking of myosin head
What does the sarcoplasm contain?
What are 'cross-bridges'?
The globular myosin heads protruding from myosin filaments
When do the following events occur:
• Cocking of myosin head
• Breakage of cross-bridges
Cocking of myosin head: ATP hydrolysis
Breakage of cross bridges: new ATP binding to myosin head
Powerstroke: ADP and Pi release from myosin head
Describe the events that lead to muscle contraction
1. Motor neuron ACh release onto motor end plate
2. ACh binds to nAChR
3. Change in nAChR conformation → influx of Na+ ions into muscle fibres
4. Initiation of post-synaptic action potential in muscle
5. AP travels along T (transverse) tubules until it reaches sarcoplasmic reticulum
6. AP changes permeability of SR → Ca2+ ions flow into sarcomere
7. Ca2+ binds troponin → tropomyosin pulled away to reveal myosin binding site on actin
List some of the supporting proteins for the myofibrils
• Dystrophin-associate glycoprotein complex
• Emerin, lamin A (proteins of the nuclear envelope)
Describe muscle metabolism
ATP as energy
Sources of ATP:
1. Within fibre
• Enough for muscle contraction for a few seconds
2. Creatine phosphate
• High energy molecule stored in muscle cells
• Transfers its high energy phosphate group to ADP to form ATP
• Enough ATP generated to maintain contraction for 15 seconds
3. Glycogen stored within cells
• Glycogenolysis → glucose
• ATP then generated from glucose
4. Glucose and fatty acids form blood stream
• Liver glycogen broken down into glucose
• Fatty acids from adipose cells and liver
• ATP generated from these by cellular respiration
What is CrPo4?
Creatine phosphate 4
High energy molecule
Transfers its high energy phosphate group to ADP to form ATP
Compare the various pathways of cellular respiration
1. Anaerobic (glycolysis)
• No O2 present, i.e. does not require oxygen
• Glucose → pyruvic acid → lactic acid
• Only 2 ATP generated
• Lactic acid diffuses into blood, and then to the liver, where it is converted back to pyruvic acid
(in the presence of O2 this can be oxidised into mitochondria)
• Occurs in cytosol
2. Aerobic (oxidative)
• Pyruvate & fatty acids → CO2 and H20
• Requires oxygen
• Occurs in mitochondria
• Produces 36 ATP
• Slower than anaerobic respiration
What happens when ATP from creatine phosphate is depleted?
Anaerobic respiration forced to begin
How long can anaerobic respiration provide ATP?
Describe the timeline of cellular respiration in muscle
1. ATP/Cr system
2. Anaerobic respiration - 30 secs
3. Aerobic respiration
-- oxygen depleted --
4. Anaerobic respiration may still support further muscle contraction
5. Accumulation of lactic acid and depletion of ATP, O2 and glycogen lead to muscle fatigue → halted muscle contraction
What is the first thing to be depleted in the muscle?
What energy production system takes the longest to kick in?
Compare fibre types in skeletal muscle
Type I: red fibres
• Slow oxidative
• Slow twitch
• Fatigue resistant
• Large amount of myoglobin
• Many mitochondria
• Many blood capillaries (i.e. good blood supply)
• Slow rate of ATP splitting
• Aerobic respiration
• Slow contraction velocity
• Found in postural muscles
Type IIA: 'red' fibres
• Fast twitch 'A'
• Fatigue resistant (but not as much as Type I)
• Large amounts of myoglobin
• Many mitochondria
• Many capillaries
• High ATP generation capacity by oxidation
• Great rate of ATP splitting
• High contraction velocity
Type IIB: 'white' fibres
• Fast twitch B
• Low myoglobin content
• Few mitochondria
• Few capillaries
• Large amount of glycogen
• Great rate of ATP splitting
• Anaerobic glycolysis
Which types of muscle fibres contain large amounts of myoglobin?
Which are the fast twitch, fatigue resistant muscle fibres?
Compare the types of physical activity enabled by the various types of muscle fibres
Type I: endurance running
Type IIA: middle distance running, swimming
Type IIB: sprinting
Describe different muscle fibre composition of different muscles
What can change the proportions?
Individual muscles are a mixture of all 3 types of muscle fibre
Proportions vary depending on action of that muscle
Exercise can induce changes:
• Endurance athletes have more type I fibres
• Sprinters have more type IIB fibres
Describe the sex and age dependence of muscle fibre distribution
No sex or age differences
i.e. N° of mucles fibres constant throughout life
Describe muscle fibre participation in various movements
Weak contraction: only type I motor units activate
Stronger contraction: type IIA + type I
Maximal contractions: type IIB/X fibres
Muscle tissue also is a major organs giving rise to heat in the body
What does multinucleate cells indicate?
Multiple cells have fused to form the muscle fibres
These precursors are called myofibroblasts
What are the boundaries of the sarcomere?
From on Z disc to another
What are I bands?
Region containing only actin filaments
Spans ends of two sarcomeres
Decreases in length in muscle contraction
What are the A bands?
Length of the myosin filaments
Doesn't change size in muscle contraction
What is the H zone?
Disappears in muscle contraction
What are the:
Bands: I and A
Which filaments are attached to the Z discs?
Which filament has a globular protein head?
Characterise the formation and breaking of the myosin heads to actin
If it happened synchronously, the actin fibres would slip out
What are T-tubules?
Pores that extend from the muscle fibre surface into the sarcoplasm and SR
Which fibre types are low in mitochondria, myoglobin and capillaries?
Which fibre types are important in postural muscles?
Type I fibres
Which fibre types are fatigue-resistant?
What is the only thing that changes muscle fibre type distribution?
Age and sex do not affect composition