Biochemistry of Muscle Contraction Flashcards
What is the muscle cell?
- the myocyte is extremely specialised
- multi-nucelated
- forms myocytes of muscle fibres
What are the two filaments called in the sarcomere?
actin (+ tropomyosin and troponin) (thin) and myosin (thick)
What is sliding filament model?
- when the sarcomere contracts, the lengths of the thick and thin filaments do not change but their overlap increases
- therefore contraction is caused by the active sliding of thick and thin filaments past each other
What is myosin?
- consists of two large heavy chains and four small light chains
- light meromyosin forms filaments spontaneously
- heavy meromyosin forms cross bridges and S1 sub fragments hydrolyses ATP and binds actin
- myosin is an enzyme
What is actin?
- main component of thin filaments and exists in two 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
What happens during muscle contraction?
- rest: no myosin/actin binding
- muscle excited: myosin heads bind actin
- conformational change in S1 creates lever arm and the power stroke (force generation)
- S1 ready for another cycle of attachment, pulling and detachment
What happens to enzymes during contraction?
- rest: ATP is hydrolysed by myosin slowly, since actin is not involved to help release ADP and Pi
- muscle excited: ADP and Pi released from active site
- active site is empty of ADP and Pi, ATP returns causing detachment of actin and myosin
How does calcium control muscle activity?
- by permitting binding of myosin to F-actin, via troponin and tropomyosin
- sub units of troponin
- Tnl binds to actin
- TnC binds to Ca2+
- TnT binds to tropomyosin
How does neural control of muscle contraction work?
- signals from neurons to muscle are carried out chemically in motor units (motor neurons and the muscle cell they innervate)
- as the motor neuron approaches muscle, it splits into hundred and thousands of branches, ending at neuromuscular junctions
What is a 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 receptor
How do signals transmit across the neuromuscular junction?
- acetylcholine released into synaptic cleft
- acetylcholine binds the 2 a subunits of the receptor and dilate its core
- many Na+ ions flow into the cytosol, with fewer K+ leaving, resulting in a depolarisation of the membrane (“postsynaptic potential”)
- 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 neurons when propogating a nerve impulse, voltage gated K+ channels open to let K+ out of the cytosol and resting membrane potential is resumed
- as opposed to Na+ and K+ voltage gated channels, the acetylcholine receptor is ligand-gated, changing its conformation only when interacting with it’s 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
What is excitation contraction (EC) coupling?
- acetylcholine mediated depolarisation of the muscle fiber stimulates the transverse tubules, an extension of the plasma membrane closely apposed to Ca2+ containing sacs called sarcoplasmic reticulum
- the reservoir of Ca2+ is maintained by Ca2+ ATPase pump which creates a steep concentration gradient across the membrane
- transmission of AP across transverse tubules causes opening of a Ca2+ channel called the ryanodine receptor
- opening thought to be via conformational change of the dihydropyridine receptor
- Ca2+ rises approx. 100 fold