Muscle development: form and function Flashcards
What are the three categories of muscle tissue?
Cardiac - only in the heart
Skeletal - throughout the body involved in moving a bone relative to a bone but in the oesophagus the muscle constricts a tube (contractility of hollow organs)
Smooth - associated with the blood vessels in the gut, uterus and the bladder
What is cardiac muscle made up of?
Functional syncytium of individual cardiac muscle cells called cardiomyosits
How are cardiac muscle fibres different to skeletal muscle fibres?
When a longitudinal section is taken
- fibres are a series of linked single cardiac muscle cells
How are cardiac muscle fibres structured?
Have an oblong structure, often in a v shape connected via the intercalated disc (mechanical and electrical function)
What are the intercalated discs made up of?
- Adherence junctions and desmosomes
- transfer mechanical force across the heart - Gap junctions which are electrical connections between adjacent cardiac muscle cells
- Arranged in contiguous sheets around the heart to give the heart its typical mechanical pumping action
How does the heart act as syncytium?
Due to mechanical and electrical connections heart has a wave of depolarisation followed by a wave of contraction
How is the desmosome structured?
Surrounded by actin filaments (normally a white band) and myosin filaments (normally a grey band) then another actin filament
What is the M line?
Centre of the myosin
What is the Z line?
Centre of actin which defines where the sarcomere is
Describe the structure of smooth muscle?
Look of visible cross striations
- cells are much smaller than skeletal muscle fibres (30-200 microns compared to up to 30 cm)
What is the primary control of smooth muscle contraction?
Control of the autonomic nervous system
Describe the structure of Multi-unit smooth muscle
Each individual smooth muscle cell has a direct innervation, continuous activity (tonic activity) - arteries and arterioles
Describe the structure of single-unit smooth muscle
Greater number of gap junctions between each other, do not require individual innervation
How to tell the difference between relaxed and stimulated smooth muscle cells?
Stimulated = Ovoid cell Relaxed = spindle shaped cell
What are the components of skeletal muscle?
Epimysium = covers the whole muscle Perimysium = covers fascicle Endomysium = basement membrane and extracellular matrix Sarcolema = muscle cell membrane
How to identity syncitial cells from a histology slide?
Multinucleated
What nerve is each muscle fibre innervated by?
Nerves from motor neurones - cell bodies in ventral part of the spinal cord
Describe the structure of the neuromuscular junction
Specialised structure
- mitochondria can be seen in the end of the nerve terminal
- underneath cell membrane = highly modified muscle cell membrane which with the nerve terminal forms the motor end plate
- circular objects = synaptic vesicles
Describe the structure of the muscle fibre membrane
- Many receptors for the extracellular matrix proteins
- Alpha dystroglycan highly glylosylated peripheral membrane
- Integrins - heterodimeric transmembrane proteins that mediate cell-matrix as well as cell-cell adhesion. specific forms in muscle:
- substrate specificity is determined by 𝛂 subunit specificity e.g. 𝛂7𝛃1 heterodimer is the major laminin-binding integrin in muscle (𝛂7𝛃1-laminin 2 in muscle)
What is the extracellular matrix made up of?
Lots of type 4 collagen, lamins, proteoglycan perlelcan and other molecules
- allows muscle fibres to exist in a harmonious state
What is myogenesis?
formation of muscular tissue, particularly during embryonic development
- somite = dermatome, sclerotome, epaxial (produces muscles of the back) and hypaxial (produces muscles of the flank, thorax, abdomen and limbs) myotome
What role do muscle progenitor cells play in the formation of myotube?
- Muscle progenitor cells are shed from myotome and migrate to muscle formation sites
- Once close differentiate into myoblasts
- Committed myoblasts
- Fuse to form a myotube
What occurs when PAX 3&7, myoD & myogenin are absent in the formation of myotube?
myoD and Myogenin are the muscle determining genes also transcription factors
- absence of both leads to deficit in skeletal muscle
What is myogenesis controlled by?
Coordinated expression of muscle specific transcription factors
In 1st round, myoblasts line up and fuse to form primary muscle fibres
Primary muscle fibre is used as a scaffold for formation of secondary myofibres
Which myogenic factors control skeletal muscle formation at which sites?
All muscle cells express a core set of myogenic factors e.g. Myogenic factor 5 (MYF5) muscle specific regulatory factor 4 (MRF4). myoblast determination protein (MYOD) and myogenin, which are required for myogenic differentiation
- other transcription factors reflect linage - specific differences and are necessary for the activation of myogenic factors and/or proliferation and survival of muscle progenitor cells
What are satellite cells?
A muscle stem cell
- develop at the same time as myotubes
- closely attached to the muscle fibre but not a part of it
How does longitudinal growth of muscle fibres occur?
Sarcomeres are added to the ends of muscle fibres with fusion of myogenic cells produced by satellite cells
How does transverse growth of muscle fibres occur?
Fusion of the myogenic cells produced by satellite cells along the length of the fibre
What does muscle fibre damage cause?
segmental necrosis
How is segmental necrosis repaired?
Satellite cell activation, differentiation and fusion
- in response to damage satellite cells divide and produce myoblasts which fuse with the muscle fibre or enter the empty space left by damage and fuse together in a very similar pattern to development
One cell must assume a quiescent state as a replacement
What is muscular dystrophy?
Caused by mutations in genes encoding for proteins of:
- extracellular matrix - absence of lamin-𝛂2
- muscle fibre membrane (sarcolema)
- contractile apparatus
- Cytoskeleton - beneath the membrane, anchoring myofibrils
Characterised by necrosis and a failure to adequately regenerate muscle
