How do muscles contract?

Cross bridge cycle (Molecular fundament) Skeletal muscle fibres remain at rest until a new contraction is generated → signal from a motor neuron, connected to the sarcolemma by a junction, resulting into a neuromuscular junction (synapse connection)

✓ ACh, neurotransmitter, hence diffuses to the sarcolemma and contacts adjacent muscle fibres ✓ stimulates ACh receptors, initiating an electrical impulse or excitation, and action potential firing deep in the T tubules → Ca2+ release from SR

Muscle contraction: cross bridge cycle

1. ACh receptors (concentrated at the crest of the postsynaptic folds) locally DEPOLARISE the membrane (+) because of the neurotransmitter release

2. Voltage-gated Na+ channels convert this depolarisation into action potential propagation away from the neuromuscular junction

3. T tubules carry the action potential deep into the myofibril

4. This activates DHP receptors (dihydropyridine receptor, voltage-dependent calcium channel), which in turns further opens RyR (ryanodine) receptors → Ca2+ release from SR

5. Ca2+ binds to actin in the thin filaments and the cross bridge cycle begins

- calcium ions released from SR bind to tropnin in thin filament, allow tropomyosin to shift, blocking active sites of actin molecules

Cross bridge cycle ceases and muscle relaxes

1. Once the action potential ceases, membrane is no longer depolarised, and DHP receptors deactivate 2. RyR receptors close and Ca2+ stops 3. Hence, there is low cytosolic Ca2+ concentration, and the cross bride cycle ceases

1. The cross bridge cycle is the molecular basis of the sliding filament 2. During the cross bridge, myosin heads bend, pulling the thin filaments 3. Then, each myosin head detaches, binding to the next active site and hence pulling again

Sources of energy for muscle contraction

Steady supply of ATP is needed for muscle contraction and relaxation ✓ Crossbridge cycle ✓ SERCA pumps activity ✓ Na+/K+ ATPase (restore Na+ and K+ intracellular levels)

Sources of energy for muscle contraction

• Stored ATP within the muscle is low (4 mM), it will not be sufficient for constant contraction… where do we get ATP from?

▪ High energy to break bond between creatine and phosphate group → energy released is used to add a P group to ADP ▪ 5-10 seconds only

▪ Glycogen is stored in liver cells (provide glucose) and skeletal cells ▪ Glucose 6 P will be used by glycolysis to generate energy ▪ This will generate lactic acid (muscle fatigue) so it is discarded ▪ 5-10 minutes only!

Oxidative phosphorylation

▪ Long but effective process ▪ Useful for long term contraction ▪ Metabolism of proteins, Aa, and fatty acids → energy ▪ 2-3 hours!

Myotendinous junction (MTJ)

- muscle tendon attachment Key roles: Intermediate in transmitting the forces from muscle fibres to the tendon Allows for muscle contraction and forces to be transmitted to the skeletal system

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Human Phys

Muscles II

Question	Answer
How do muscles contract?	Cross bridge cycle (Molecular fundament) Skeletal muscle fibres remain at rest until a new contraction is generated → signal from a motor neuron, connected to the sarcolemma by a junction, resulting into a neuromuscular junction (synapse connection)
Cross bridge cycle	✓ ACh, neurotransmitter, hence diffuses to the sarcolemma and contacts adjacent muscle fibres ✓ stimulates ACh receptors, initiating an electrical impulse or excitation, and action potential firing deep in the T tubules → Ca2+ release from SR
Muscle contraction: cross bridge cycle	1. ACh receptors (concentrated at the crest of the postsynaptic folds) locally DEPOLARISE the membrane (+) because of the neurotransmitter release
Muscle contraction	2. Voltage-gated Na+ channels convert this depolarisation into action potential propagation away from the neuromuscular junction
Muscle contraction	3. T tubules carry the action potential deep into the myofibril
Muscle contraction	4. This activates DHP receptors (dihydropyridine receptor, voltage-dependent calcium channel), which in turns further opens RyR (ryanodine) receptors → Ca2+ release from SR
Muscle contraction	5. Ca2+ binds to actin in the thin filaments and the cross bridge cycle begins
In detail	- calcium ions released from SR bind to tropnin in thin filament, allow tropomyosin to shift, blocking active sites of actin molecules
	- each myosin head binds to active site on thin filament, displaces ATP remenants ADP and Pi (inorganic phosphate)
	- energy released pulls actin and heads back to original position - remains here until ATP pulls back to resting position
	- each myosin head in thick filament moves to resting position after ATP binds and moves it back to resting position
Cross bridge cycle ceases and muscle relaxes	1. Once the action potential ceases, membrane is no longer depolarised, and DHP receptors deactivate 2. RyR receptors close and Ca2+ stops 3. Hence, there is low cytosolic Ca2+ concentration, and the cross bride cycle ceases
	4. SERCA pumps drive Ca2+ back into the SR, therefore contributing to resting level, low cytosolic Ca2+ concentration and muscle relaxation
Sliding filaments	1. The cross bridge cycle is the molecular basis of the sliding filament 2. During the cross bridge, myosin heads bend, pulling the thin filaments 3. Then, each myosin head detaches, binding to the next active site and hence pulling again
Sources of energy for muscle contraction	Steady supply of ATP is needed for muscle contraction and relaxation ✓ Crossbridge cycle ✓ SERCA pumps activity ✓ Na+/K+ ATPase (restore Na+ and K+ intracellular levels)
Sources of energy for muscle contraction	• Stored ATP within the muscle is low (4 mM), it will not be sufficient for constant contraction… where do we get ATP from?
Creatine phosphate	▪ High energy to break bond between creatine and phosphate group → energy released is used to add a P group to ADP ▪ 5-10 seconds only
Glycolysis	▪ Glycogen is stored in liver cells (provide glucose) and skeletal cells ▪ Glucose 6 P will be used by glycolysis to generate energy ▪ This will generate lactic acid (muscle fatigue) so it is discarded ▪ 5-10 minutes only!
Oxidative phosphorylation	▪ Long but effective process ▪ Useful for long term contraction ▪ Metabolism of proteins, Aa, and fatty acids → energy ▪ 2-3 hours!
Myotendinous junction (MTJ)	- muscle tendon attachment Key roles: Intermediate in transmitting the forces from muscle fibres to the tendon Allows for muscle contraction and forces to be transmitted to the skeletal system
	MTJ has a specialised ECM that differs from tendons and muscles Collagen type I (but also III, IV, V, VI, XII, XIV), proteoglycans including decorin, versican, lumican, and glycoproteins including tenascin, COMP, elastin

Created by: reub8n

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