Lecture 31 - Muscular Dystrophies - Muscle Structure, Function and Neuromuscular Transmission Flashcards
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
Myopathies:
• Genetic and acquired disorders of the muscle contractile apparatus (thick, thin filaments etc)
• Generally static pathology
Muscular dystrophies:
• Genetic disorders of the supporting structures (DAPC)
• Progressive degeneration
e.g.
• Sacrolemmal proteins
• Proteins which anchor the contractile apparatus in place
Outline these features of skeletal muscle:
• Location
• Function
• Structure
Talk about the variation seen in these features
• Attached to bone
Function
• Voluntary control
• Different contraction velocities depending on ability
• Variable metabolic processes used to generate energy
Structure:
• Made up of muscle fibres (the cells)
• Striated
• 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
Skeletal muscle:
• Myofibres: parallel muscle fibres grouped into bundles
• Sacromeres
Smooth:
• Involuntary
• Not striated
NB both are:
• Multinucleated
• Contractile
Describe muscle fibres in detail
Hierarchy:
Muscle belly - Epimysium - Perimysium - Fasciculus - Endomysium - Muscle fibres (cells) - Myofibrils within cells
Fasciculi: bundles of muscle fibres
Muscle fibres: the cells Consists of: • Sarcolemma (membrane) • Myofibrils: contractile component • Sarcoplasm • Multinucleated
What is the sarcolemma?
The membrane of muscle fibres
Compare the location of the following:
• Epimysium
• Perimysium
• Endomysium
These are all cocnective tissues surrounding various structures
Epimysium:
• Ensheaths entire muscle
Perimysium:
• Ensheaths fasciculi
Endomysium:
• 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
Structure:
• 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)
• Troponin
• Tropomyosin: weaved around the actin filaments
Describe the sliding filament model of muscle contraction
At rest:
• Tropomyosin covers myosin binding sites on actin
Muscle contraction:
- Ca2+ influx into cytoplasm and binds to troponin
- Tropomyosin moves, revealing myosin binding sites on actin
- Myosin heads bind to actin forming cross bridges
- Release of ADP and Pi
- Conformational change of myosin head: powerstroke
- Actin pulled into the centre of the sarcomere: Z discs pulled into centre
- ATP binds myosin head, cross-bridge breaks, myosin returns to unattached position
- ATP hydrolysis brings about cocking of myosin head
What does the sarcoplasm contain?
Glycogen
Fat particles
Enzymes
Mitochondria
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
• Powerstroke
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
- Motor neuron ACh release onto motor end plate
- ACh binds to nAChR
- Change in nAChR conformation → influx of Na+ ions into muscle fibres
- Initiation of post-synaptic action potential in muscle
- AP travels along T (transverse) tubules until it reaches sarcoplasmic reticulum
- AP changes permeability of SR → Ca2+ ions flow into sarcomere
- 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
- Sarcoglycans
- Dystrophin
- 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
- 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 - Glycogen stored within cells
• Glycogenolysis → glucose
• ATP then generated from glucose - 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