MSS: Muscle Structure & Adaptation Flashcards
Where is muscle formed from?
During embryogenesis muscle is formed from the somites (paraxial mesoderm)
Describe how the initial muscle is formed
Paracrine signalling from the notochord triggers a mesenchymal → epithelial transition forming the somite (Hollow ball of epithelial cells)
Explain the formation of the 4 muscle cell subtypes
Paracrine signals (e.g. hedgehog /Wnt signalling from neural chord to notochord) causes a epithelial → mesenchymal transition causing the formation of 4 types of cell groups that form very specific tissue types
What are the 4 subtypes of muscle cells?
Sclerotome (bone, ribs cartilage)
Myotome (muscle precursors)
Syndetome (tendons) between myotome and sclerotome
Dermomyotome (myotome and dorsal dermis) - external; as embryo develops provides new muscle cells
How do the muscle cell types cause movement?
As these differentiate they interact with one another to cause movement
Where do myotome cells originate from?
Myotome cells develop from mesodermal cells
What causes the initiation of muscle formation?
Paracrine signalling factors (hedgehog / FGF) induce transcription of myogenic regulatory factors: Myf5 and MyoD = myogenic commitment (myoblasts)
What causes myoblast proliferation?
Myoblast proliferate due to growth factors
How do myoblasts exit the cell cycle?
Cell cycle exit due to Myogenin expression = terminal differentiation to form tubes and structural proteins are expressed
How are muscle fibres formed?
Myotubes align and fuse to form muscle fibre (multinucleated)
Why is muscle formation known as a biphasic process?
Biphasic muscle development: Primary (forms architecture for other muscle fibres to form) and Secondary fibres (bulk of muscle)
What is the role of satellite cells?
Satellite cells: regeneration and postnatal growth (muscle stem cells)
A pool of MuSCs are quiescent and are dormant until activated to contribute to muscle cell size
How do satellite cells contribute to muscle regeneration?
Dormant on muscle fibres until activated in case of muscle regeneration where they divide and form myotubes and fuse to muscle fibre
When they divide they leave a pool of cells in place to be activated later
What determines the embryonic fibre number?
Fibre number is set at birth - genetically determined
What are the 2 ways of increasing fibre number?
Can increase fibre number - hyperplasia
Hypertrophy increases muscle mass postnatally
What are the factors affecting fibre number?
Temperature
Hormones
Nutrition
Innervation
These factors affect MRF (myogenic regulatory factors) expression duration
What are MRFs?
myogenic regulatory factors
MRFs are transcription regulatory factors - go on to induce transcription of structural proteins when expressed
Why does muscle mass increase after birth?
After birth, increase in muscle mass due to increase in fibre size (hypertrophy) (increases muscle cell size)
What cells are responsible for hypertrophy?
Muscle stem Cells (MuSCs) called Satellite cells required for hypertrophy. These are present on the muscle cell surface
What triggers hypertrophy to occur?
During growth the muscle fibres require more protein, causing stem cell division and fusion with myofiber and start producing more structural proteins => increases cross section and size of muscle fibre
Describe the structure of muscle fibres
Muscle fibres are multinucleated
Maintain cytoplasm : nuclei ratio as muscle fibre requires lots of mitochondria and structural proteins along the length of the muscle cell
Nuclei are present along the cell to produce the required cell structures
What is hyperplasia?
(After birth) increase in muscle mass due to increase in cell/fibre number (hyperplasia)
Proposed mechanism: fibre splitting and SC activation
What is the main contributor to increasing muscle mass in humans?
Evidence that this occurs in humans in lacking but most probably does. - hypertrophy is the main factor
What is the reason for muscle fibre-type diversification?
All vertebrate sarcomere structure the same
Molecular variability depending on muscle type and function due to different muscle isoforms
What causes the formation of multiple isoforms?
Multiple isoforms of myofibrillar proteins due to Alternative splicing or promoters
What are the different isoforms present?
Titin isoforms
- elastic properties
Troponin & Tropomyosin isoforms
- determine Ca2+ sensitivity (SR) → resistance to fatigue
Myosin isoforms
- different chemomechanical transduction, ATP hydrolysis,. - Shortening velocity → resistance to fatigue
What are Type I fibres?
Slow muscle: (e.g. back extensor muscles)
Describe the structure and function of type I (slow) fibres
High mitochondria: aerobic
Virtually inexhaustible
Oxidative phosphorylation
Extensive blood supply and abundant myoglobin
What are type II fibres?
Fast muscle; brachioradialis
Outline the features of fats twitch muscle fibres
Fatigues easily
Few mitochondria: mainly anaerobic metabolism
Glycolytic
Poor vascularization and lack myoglobin
Describe the fast:slow muscle ratio in different trained levels individuals
Untrained individuals 50:50 ratio of fast (IIA and IIX) to slow (I) twitch fibres
Long and middle distance runners: 60-70% slow
Sprinters: 80% fast twitch
Explain the type of muscle fibre required for different forms of exercise
Sports requiring greatest aerobic and endurance capacities: slow muscle upto 90-95%
Sports with greater anaerobic capacities (strength and power) have fast muscle from 60-80%
Outline the muscle adaptations seen in a marathon runner
Muscles small but fatigue resistant Muscle dense and strong for their size High oxidative capacity of muscles Work over very long periods of time Not explosive strength
Describe the muscle adaptations of sprinters
Muscles adapted for explosive release of force:
Rapid powerful contractions
Easily fatigued at maximum effort
Low oxidative capacity via mitochondria
High force per cross-sectional area of muscle
What are the ways muscles are adapted for powerlfiting?
Muscles are hypertrophied Highly glycolytic Fatigue easily High muscle to total body mass ratio Muscle size beginning to interfere with locomotion
Why is a powerlifter not good at running?
Thus the powerlifter is moving along the same path of adaptation as the sprinter but is more extreme
His power to weight ratio is moving to a point where he is less able to move his body through a distance and hence would be less fast at running
What is the myosin gene cluster?
Myosin sits in a chromosome in a cluster of myosin genes, which allow for the different isoforms giving the different properties of the muscle fibres
What are the 3 types of myosin genes in adults?
Adults have 3 main types of myosin: 2A, 2X and slow muscle:
- MHCIIa also called MHC2A
- MHCIIX/d also called MHC2X/d
- MHCIIb also called MHC2B
What are the other myosin gene forms in humans?
MHCemb - embryonic myosin
MHCperi - perinatal myosin
MHCexoc - extraocular
What varies between the myosin isoforms?
Each MHC isoform is able to split ATP at different rates in the order:
fastest 2B > 2A > 2X > 1> embryonic slowest
How does muscle composition differ in males and females?
> 3000 genes different between male and female skeletal muscle
Differences in myosin isoforms:
Females have more slow muscle fibres
Males have more fast muscle fibres
Type I (slow) M: 36% F: 44%
Type IIA (fast) M: 41% F: 34%
Males ♂: larger fibre cross sectional area (CSA) - muscle more easily hypertrophied than women
What is the role of testosterone?
Primary male sex hormone: required for the development of the male reproductive system
Promotes secondary sexual characteristics: muscle+bone mass, body hair, deep voice
What type of hormone is testosterone?
T is a natural anabolic-andronergic-steroid (AAS)
How does testosterone promote muscle production?
Promotes the commitment of mesenchymal pluripotent cells into myogenic lineage and inhibit adipogenesis
(androgen receptor mediated pathways)
Muscle differentiation > fat cells
Stimulates: increased satellite cell replication, muscle protein synthesis, fibre hypertrophy
What are the consequences of using synthetic anabolic steroids?
> irreversible adverse effects
High BP, cardiac & liver problems etc.
What may cause muscle injury?
Skeletal muscle injuries can stem from direct trauma such as muscle lacerations
and contusions, indirect insults such as strains and also from degenerative diseases such as muscular dystrophies
How does muscle respond to injury?
Muscle has regenerative property if not too severe - otherwise can get fibrosis and scar tissue - impairs muscle function
Outline the reparation that occurs in a normal muscle tear
Normal tear:
- Tissue necrosis
- Haematoma forms (blood fills wound area)
- Division of satellite cells; use haematoma to fuse and
build upon - Increased Myf5 & MyoD expression - myogenin causes
differentiation and formation of structural proteins,
sarcomeres and muscle fibres will self renew - Process of vascularisation and synaptic innervation -
homeostasis then occurs
what are the 3 main phases of muscle regeneration?
- Degeneration/inflammation phase: (first few days)
- Regeneration Phase: 4-5 days pi.
- Remodeling phase: 2/3 wks
Explain the degenration/inflammation phase
Myofibre rupture and necrosis, formation of hematoma, inflammatory response.
What happens in the regeneration phase?
Phagocytosis of damaged tissue, SC activation and proliferation
What occurs in the remodelling phase at 2/3wks?
maturation of regenerated myofibers, restoration of blood supply and innervation, recovery of muscle functional capacity and also fibrosis and scar tissue formation
What is sarcopenia?
age related loss of muscle mass
3-8% decrease per decade after the age of 30, higher after 60
Impact on the elderly: falls, injury, disability
What is a loss in muscle mass associated with?
Loss of muscle mass associated with gain in fat mass
Associated with decreased satellite cell number and recruitment
What are the biochemical and metabolic changes that contribute to a reduction in muscle mass?
Biochemical and metabolic changes:
Mitochondrial mutations
Reduced oxidative + glycolytic enzyme activity
Reduced endocrine function, reduced physical activity
What is the role of MRFs?
Regulation of Myogenic commitment and terminal differentiation
What are the myoblasts developed from?
Myoblasts develop from myogenic precursor cells which are of mesodermal origin
What is skeletal muscle composed of?
Skeletal muscle is formed from a network of muscle tissue, connective tissue, nerves and blood vessels
What is the significance of satellite cells?
Satellite cells (MuSCs) are fundamental for repair, regeneration and maintenance of muscle
