Skeletal Muscle Flashcards
What factors control muscle mass?
nutritional status, hormones, genetics, innervation, inflammation, oxidative stress, blood flow, exercise, disease
What are the different muscle fibre types
Type I - slow twitch and Type IIa and IIx - fast twitch
What is a pure muscle fibre?
one that contains only one type of heavy chain myosin vs hybrids which contain multiple forms
What are the goals of interventions for muscle wasting disorders?
attenuate muscle atrophy, increase muscle strength without increasing muscle fatigue
What is myostatin?
a negative regulator of muscle mass
What are the different types of muscle atrophy?
disuse atrophy, denervation atrophy, disease states e.g. cancer cachexia
What percentage of cancer related deaths are attributed to cachexia?
20%
What is sarcopenia?
age related muscle wasting associated with loss of mass and function
What are the causes of sarcopenia?
disuse, changing endocrine function, chronic diseases, inflammation, insulin resistance, nutritional deficiencies
How is sarcopenia diagnosed?
gait speed of less than 1m/s and a lean to fat ratio of less than 2 SD of the average young adult - or a loss of muscle mass combined with low muscle strength and or low physical performance
Can sarcopenia be stopped with healthy behaviours?
no
What is weakness?
an inability to develop an initial force appropriate for the circumstance
Are fast or slow muscles more affected by ageing?
fast muscles
What is age related motor unit remodelling?
denervation of type II motor units and reinnervation with type I motor units - leads to slowed contraction
What happens to motor neurons with age?
demyelination, small diameter axons, increase in connective tissue in nerves
What happens to the NMJ with age?
longer nerve terminals, fewer side branches, widening of end plate
Can the effects of ageing on muscle be attenuated?
yes - through strength training before 50 years of age
Decreased circulating levels of what hormones contribute to changes in muscle size and strength?
testosterone, GH, IGF-1
What is the age of onset of duchenne muscular dystrophy?
2-6 years old
What are the symptoms of duchenne muscular dystrophy?
generalised weakness and muscle wasting affecting limb and trunk muscles first - calves often enlarged
What is the progression of duchenne muscular dystrophy?
disease progresses slowly - affects all voluntary muscles - rarely survive beyond late twenties
What is the inheritance of duchenne muscular dystrophy?
X-linked recessive
How many newborn males are affected by DMD?
1 in 3500-6000
How many cases of DMD are a result of a new mutation?
1 in 3
What gene is mutated in DMD?
dystrophin
What is the dystrophin associated protein complex?
a series of transmembrane proteins associated with dystrophin which maintain the architecture of the muscle fibre as well as being involved in cell signalling
How is dystrophin bound to the cytoskeleton?
via binding with F-actin
What happens to muscles in the absence of dystrophin?
muscle membranes will be highly fragile and there will be decreased muscle signalling
What is the age of onset of becker muscular dystrophy?
adolescence or adulthood
What are the symptoms of becker muscular dystrophy?
same as DMD but less severe
What is the progression of BMD?
disease progresses slowly but will affect all voluntary muscle - survive into mid to late adulthood
What is the inheritance of BMD?
X-linked recessive
What gene is affected in BMD?
dystrophin
What is the difference between DMD and BMD?
in DMD there is a deletion in the gene which causes a frame shift so there is only synthesis of very small fragments - in BMD the reading frame is preserved so larger more useful portions of dystrophin are synthesised
Why does a lack of dystrophin lead to degeneration of skeletal muscle?
a loss of dystrophin will lead to disorganised costameres, membrane leak, increased oedema, inappropriate cytosolic calcium and ROS generation and increased extracellular matrix deposition around myofibres
What are the different ways to treat muscular dystrophy?
gene therapy, stem cell therapy or pharmacological intervention
What drugs are available for muscular dystrophy?
corticosteroids, anabolic steroids, beta 2 agonists, IGF-1, myostatin inhibitors, proteasome inhibitors, membrane sealants, vitamin E, calcium channel blockers, heat shock protein induction
