Biochemistry of muscle contraction (wk2)

Question 1

Identify and describe the unique features of the muscle cell
(Muscle cell, muscle fibres, striated appearance)

Answer 1

-Muscle cell -> The myocyte is extremely specialised. Unlike other cells, it is multi-nucleated due to fusion of myoblasts during development. Form myotubes, or muscle ‘fibres’.
-Muscle fibres – Filled with 1000 parallel rods of contractile material packed in cytosol (microfibrils)
-Striated appearance in ‘flight muscle’ in the proteins

Question 1

Describe the sliding filament theory of muscle contraction and the biochemical processes involved
(High E. Huxley)

Answer 1

-Hugh E. Huxley 1924-2013 -> ‘when the sarcomere contracts, the lengths of the thick and thin filaments do not change, but their (degree of) overlap increases’. Therefore, contraction is caused by the active sliding of thick and thin filaments past each other.

Question 2

Describe the properties of contractile proteins that facilitate movement

Answer 2

-Thick and thin filaments overlap and are composed of contractile proteins
-Thick -> mostly myosin + Thin -> mainly actin, tropomyosin and troponin
-M – line -> myomesin and M-protein
-Z – line -> (symbol)-actinin

Question 3

Describe the properties of contractile proteins that facilitate proteins
(myosin, actin, myosin isoforms and fibre type, control of muscle activity by Ca2+)

Answer 3

-Myosin (an essential protein in contraction) -> Very large (520kda) and very abundant in muscle. Consists of 2 large heavy chains and 4 small light chains. Lights meromyosin forms filaments spontaneously (self assembly). Heavy meromyosin forms cross bridges and S1 sub fragment hydrolyses ATP and binds actin (myosin is an enzyme ATPase).
-Actin -> Main component of thin filaments and exists in 2 forms: G-actin (globular) and F-actin (fibrous). F actin monomers intertwine and form the trunk of thin filaments to which tropomyosin and troponin attach. F actin greatly increases ATPase activity of myosin by increasing the rate at which ADP and Pi are released from the active site.
-Myosin isoforms and fibre type -> Genes encode proteins, but variations in proteins can arise from one gene via alternate splicing or RNA editing. These variants are referred to as isoforms. Myosin displays multiple isoforms that influences muscles and ultimately, exercise performance. Adult humans have Myosin Heavy Chain (MHC) I, IIa and IIx (was IIb).
-Control of muscle activity by Ca2+ -> Calcium (non-energy nutrient) controls muscle contraction by permitting binding of myosin to F-actin, via Troponin and tropomyosin. There are subunits of Troponin. Tnl binds to actin. TnC binds Ca2+. TnT binds tropomyosin.
-Rest: Tropomyosin covers binding site on actin

Question 4

Describe the cellular structures, proteins and processes that regulate the neural control of muscle contraction
(neural control of muscle contraction and the neuromuscular junction)

Answer 4

-Neural control of muscle contraction -> Signals from neurons to muscle are carried out chemically in motor units (motor neurons and the muscle cells they innervate). As the motor neuron approaches muscle, it splits into hundreds and thousands of branches, ending at neuromuscular junctions.
-Neuromuscular junction -> Each junction contains many synapses, where a neurotransmitter, Acetylcholine is discharged when action potentials arrive at the pre-synaptic membrane. Signal is carried in muscle thanks to acetylcholine receptors.

Question 5

Draw the signal transmission across the neuromuscular junction

Question 6

Describe the 4 steps of the signal transmission across the neuromuscular junction

Answer 6

• The postsynaptic potential is aided by voltage gated Na+ channels in the plasma membrane that facilitate Na+ entry after depolarisation
• As is the case in neurones when propagating a nerve impulse, voltage gated K+ channels open to let K+ out of the cytosol and resulting membrane potential is resumed
• As opposed to Na+ and K+ voltage gated channels, the acetylcholine receptor is ligand-gated, changing it’s conformation only when interacting with its ligand (acetylcholine)
• After the excitation has passed, free acetylcholine is hydrolysed in the synaptic cleft by acetylcholinesterase and the receptor returns to its original conformation

Question 7

Draw the excitation contraction coupling and the cellular processes involved

Question 8

Describe the linking neuron to muscle contraction (EC coupling)

Answer 8

-Linking neuron to muscle contraction (EC coupling) -> Acetylcholine mediated depolarisation of the muscle fibre stimulates the transverse tubules, an extension of the plasma membrane closely apposed to Ca2+ containing sacs called the sarcoplasmic reticulum. The reservoir of Ca2+ is maintained by Ca2+ ATPase pump which creates a steep concentration gradient across the membrane

Question 9

Describe linking the neuron to muscle contraction (EC) coupling

Answer 9

-Linking neuron to muscle contraction (EC) coupling -> Transmission of AP across transverse tubules causes an opening of Ca2+ channel called the ryanodine receptor. Opening thought to be via conformational change of the dihydropyridine receptor. Ca2+ rises approx. 100 folds

Question 10

Describe the distribution in calcium handling

Answer 10

-Disruption in calcium handling -> Ryanodine is a poison that binds with high affinity to the ryanodine receptor. It blocks calcium release from the SR, resulting in paralysis. A lack of activity of the Ca2+ ATPase means resting gradient cannot be restored, leading to rigor mortis

Question 11

Describe the passing of the action potential and relaxation

Answer 11

-Passing of the action potential and relaxation -> Binding of Ca2+ to TnC activated muscle contraction. When AP passes, Ryanodine receptor closes, preventing Ca2+ efflux from the SR, Ca2+ ATPase returns resting gradient. Energy therefore required for both contraction and relaxation (see Rigour Mortis). Myosin ATPase and Ca2+ ATPase major energy consumers in muscle.

Question 12

Describe how large is the requirement for ATP with muscle contractions (6 points)

Answer 12

• Assuming 1 ATP is used for a single actin-myosin power stroke
• There are 100’s of myosin heads in each sarcomere
• There are 100’s of thousands of sarcomeres in each much fibre
• There are approx. 250,000 muscle fibres in a muscle like the bicep
• Assuming all fibres are engaged, single muscle switch requires ~7.5 billion ATP molecules
• Demand for ATP hydrolysis during strenuous exercise can be as high as 12 heximillion molecules of ATP per minute