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what is myasthenia gravis?
causes muscle weakness, particularly in muscles of eyes, eyelids and face
Defects in signalling from nerve to muscle at neuromuscular junctions
Untreated → difficulties in swallowing and breathing
what are the 3 types of muscle?
sksletal
Cardiac
Smooth
what are the stages of muscle organisation?
filaments→sarcomere→myofibril→fibre→fasciculus→muscle
what does a muscle ultrastructure look like when relaxed?
ends of actin from Z discs barely overlap
what does a muscle ultra structure look like when contracted?
actin filemnts pulled inwards, overlap to maximum extent
Myosin molecule vs myosin filament:
myosin filament is made up of 200-300 myosin molecules
describe the structure of an actin filament:
double stranded F-actin (filamentous actin) molecules comprising polymerised G-actin molecules
2 strands of tropomyosin molecules
Troponin complex on each tropomyosin for contraction (binds Ca2+)M
How much myosin and actin is found in a myofibril?
1500 myosin filaments
3000 actin filaments
what are the contractile proteins of muscle?
myosin
Actin
what are the regulatory proteins of muscle?
tropomyosin
Troponin
what are the structural proteins of muscle?
titin
a-actinin
Myomesin
Nebulin
Dystrophin
what are the first steps of sliding filament of muscle contraction which allow contraction to be initiated?
In low Ca2+ conditions, tropomyosin blocks access to the myosin binding site of actin
In high Ca2+, Ca2+ binds to troponin
Positions of troponin and tropomyosin are altered on actin
Myosin can now access its binding site on actin
Contraction now favoured
How does the sliding filament theory take place once myosin can access its binding site?
ATP on myosin is hydrolysed to ADP and Pi, to reorientate and energise the myosin head
Myosin head attached to myosin-binding site on actin, releases phosphate
Cross-bridges form, power stroke occurs, myosin head pivots from 90→45 degree angle
ADP released. Cross bridge generates force, sliding actin past myosin
Cross bridge remains attached to actin until another ATP is bound. When ATP binds to myosin, myosin head detaches from actin
Repeats
What happens to the muscle fibres in low calcium conditions?
tropomyosin blocks access to the myosin binding site of actin
what happens to the muscle fibre in high calcium conditions?
Ca2+ binds to troponin, troponin and tropomyosin change positions, leaving the myosin binding site accessible
How does the length of the filaments change during contraction?
they do not change length, only change position relative to each other
what causes the actomyosin cross bridge to break down?
ATP binds to myosin
lenth-tension relationship depends on:
sarcomere length within a muscle before contraction begins
what is the resting length?
2.2um
Optional overlap in sarcomere, maximum tension possible
what enables optional resting muscle fibre length in skeletal muscle
tendon attachment of muscle to bon
how much tension is possible in unstretched muscle?
little
how much tension is possible at highest stretch?
no tension - actin pulled to ends of myosin - no overlap
what does excitation-contraction in skeletal muscle lead to?
skeletal muscle contraction
Generated high Ca2+ conditions needed for actin-myosin binding
what does acetylcholine bind to in the neuromuscular junction?
nicotinic receptors
Muscle action potential flows rapidly through the centre of the muscle fibre via..
the t-tubules
what senses the action potential voltage in a muscle fibres?
dihydropyridine receptors (L-type channels) on T-tubule membrane
what is the function of L-type channels on t-tubules?
trigger the Ca2+ release channels on sarcoplasmic reticulum called ryanodine receptors to open and release Ca2+ into sarcoplasm
what is the result of ryanodine receptors releasing Ca2+ into sarcoplasm?
increase in intracellular Ca2+ enable Ca2+ binding to troponin, therefore troponin and tropomyosin move, allowing binding to the myosin head
how does Ca2+ re enter the sarcoplasmic reticulum store?
calcium ATPase pump
What are the functional classifications of skeletal muscle fibres?
Type 1 - slow twitch
Type IIA - fast twitch
Type IIB - fast twitch
What are slow twitch muscle fibres?
postural muscles of back
Slow, sustained contractions
Oxidative metabolism
Many mitochondria
Red myoglobin
Resists fatigue
what are IIA fast twitch muscle fibres?
soleus in calf
Fast contractions
Oxidative metabolism
Many in mitochondria
Red-pink myoglobin
Intermediate fatigue resistance
what are fast twitch IIB muscle fibres?
extraocular muscle
Rapid contractions
Anaerobic glycolysis
Few mitochondria
White-little myoglobin
High glycogen content