Muscle Contraction Flashcards
What are the three different types of muscles?
Compare and contrast them.
- skeletal e.g voluntary motor muscle, in pairs, movement of bones e.g thigh and calf
- cardiac - located in the heart
- smooth - involuntary action of the ANS e.g the gut, digestive system
Skeletal - Striated, Multinucleate, uniform cells. 40mm. Skeletal muscle organised in bundles called fascicles made of fibres. Actin and myosin arranged in a particular banded pattern
Cardiac - Striated, Mononucleate, Branched structure, Intercalated discs between cells for free diffusion of ions. Contracts powerfully and continuously → does not tire easily → controlled by ANS.100 μm.
Smooth Muscle - Non-striated, Mononucleate, actin and myosin are arranged in a regular way. 30-100 μm
What is the purpose of the T-tubule?
What is the purpose of the sarcoplasmic reticulum?
The T-tubule brings membrane events deep within the cell for regulation and interaction with the SR. Within t-tubules, there are voltage sensing ion channels like proteins which physically interact with Ca2+ in sarcoplasmic reticulum. Present in skeletal and cardiac muscle.
Sarcoplasmic reticulum stores Ca2+
Describe skeletal muscle contraction.
- Ach binds to the nAchR
- The Na+ ion channels on the cell membrane are triggered, which causes an influx of Na+ ions into the sarcoplasm. This causes depolarisation of the cell, which brings an action potential along the sarcolemma and down the T-Tubule.
- The action potential also activates DHP receptors (dihydropyridine), which are in physical contact with the calcium release channels (ryanodine receptors) on the Sarcoplasm Reticulum (SR). When the DHPs are activated, they undergo a conformational change and open the ryanodine receptors, releasing calcium ions into the sarcoplasm.
- These calcium ions bind to Troponin in the sarcoplasm, making Ca-Troponin, which leads to contraction. Generalised contractile cycle follows.
- SERCA (Sarco/Endoplasmic Reticulum Ca²⁺-ATPase) is also present on the SR, and it is used to bring Ca2+ ions back into the SR, which leads to relaxation.
Describe cardiac muscle contraction.
- Ach binds to the nAchR
- The Na+ ion channels on the cell membrane are triggered, which causes an influx of Na+ ions into the sarcoplasm. This causes depolarisation of the cell, which brings an action potential along the sarcolemma and down the T-Tubule.
- In this case, the DHP receptors are not in physical contact with the SR, so they release some calcium ions into the sarcoplasm. This causes the ryanodine receptors on the SR to open in response to the local calcium presence. This is called Calcium-Induced Calcium Release (CICR).
- The calcium then combines with Troponin in the sarcoplasm to make Ca-Troponin, which leads to contraction. Generalised contractile cycle follows.
- SERCA (Sarco/Endoplasmic Reticulum Ca²⁺-ATPase) is also present on the SR, and it is used to bring Ca2+ ions back into the SR, which leads to relaxation.
Describe smooth muscle contraction.
- Sympathetic nerves synthesize and release noradrenaline which binds to the α1-adrenoreceptor on vascular smooth muscles.
- The α1-adrenoreceptor is linked to a Gαq/11 subunit. This activates and stimulates Phospholipase C, which catalyzes the cleavage of PIP2 to IP3 and DAG, both of which behave as secondary messengers.
- This IP3 travels down to the calcium release channels on the SR, and causes them to release Ca2+ ions into the sarcoplasm.
- Calcium ions also enter the sarcoplasm from the ECF (extracellular fluid) via voltage-dependent or receptor-mediated calcium channels. Due to the local rising calcium CICR occurs which in results causes a huge increase in calcium.
- These calcium ions then bind with calmodulin in the sarcoplasm, which then activate Myosin Light Chain Kinase. After a series of events, this leads to contraction. Contractile cycle follows (but with calmodulin rather than troponin)
Describe the generalised contractile cycle.
1) Ca2+ ions bind to troponin-C, weakening the bond between troponin and tropomyosin.
2) The troponin molecule undergoes a conformational change and changes position, rolling the ‘suppressive’ tropomyosin molecule away from active sites on actin allowing interaction with primed myosin heads (ATP hydrolysed by ATPase present on myosin head - causing kinking of myosin head and causing it to prime for interaction).
3) The active sites on actin are exposed and myosin heads bind to them, forming cross bridges. ATP is hydrolysed and initially Pi is released for tight binding of actin filament (M head binds to actin further up).
4) Myosin heads pivot towards the M line, releasing ADP. This action is known as a power stroke. Myosin undergoes a conformational change and the powerstroke causes actin to slide along the myosin and move towards centre of sarcomere.
5) Another ATP binds to the myosin heads, breaking the link between myosin and actin. The active site is exposed and able to form another cross bridge. Myosin is now primed again.
6) Myosin reactivates when the free myosin head splits ATP into ADP and a phosphate. The energy released is used to recock the myosin head and the process starts all over again.
Describe the difference between smooth muscle and other muscle.
SMOOTH MUSCLE HAS:
- the myosin contains a regulatory light chain
- there is low inherent ATPase activity
- there is no troponin, but calmodulin instead
- there’s dual regulation (with MLCK (Myosin Light-Chain Kinase)
- no T-tubules
- less developed SR
- sustain contraction for longer periods of time
Describe what happens after the activation of Myosin-Light-Chain Kinase.
The activation of Myosin-Light-Chain Kinase phosphorylates regulatory MLC at Ser 19. This increases the ATPase activity of the myosin head around 1000 fold and alters the structure of the myosin.
Describe the difference in performance between smooth and skeletal muscle.
- there’s a greater shortening in smooth muscle (because of the longer actin)
- there’s a slower speed of contraction in smooth muscle (~30x)
- there’s a lower energy requirement in smooth muscle (latch state)
What is Rigor Mortis?
Dying cells release Ca 2+ ions, which allow the binding of actin and myosin. However there is no more ATP for unbinding, so muscles stay contracted.
What is contraction?
Contraction is the interaction of actin and myosin fueled by ATP and driven by rise in [Ca2+]
What are actin and myosin sometimes referred to?
What proteins are also associated with actin?
Describe the structure of myosin
-actin: thin filament
-myosin: thick filament
PROTEINS ASSOCIATED WITH ACTIN
-tropomyosin: blocks the active site of actin in absence of calcium
-troponin C: binds to Ca2+
-troponin T: binds to tropomyosin
MYOSIN STRUCTURE
-has a head and tail
-head has 2 domains:
1) binds to ATPase which allows it to flex
2) binds to actin
How do you initiate the sliding filament mechanism?
-influx of Ca2+ from the sarcoplasmic reticulum which allows Ca2+ to bind to troponin-c
-this causes troponin T to bind to tropomyosin with pulls the tropomyosin out of the active site on actin
-this means that actin is free to bind to myosin
Outline what occurs at the neuromuscular junction
- The neuromuscular junction occurs between the nervous system and muscle. Similar to synapse (REFER TO NOTES ON SYNAPSES/ RECEPTOR MECHANISMS)
1. Action potentials arrive at end of axon → open voltage-gated calcium ion channels → influx of calcium ions down a concentration gradient from the fluid surrounding the presynaptic membrane.
2. Calcium causes vesicles of acetylcholine to move towards and fuse with the membrane.
3. Acetylcholine diffuses across junction and fuses with nicotinic ACh receptors in sarcolemma.
Suggest why β-adrenoreceptors cause smooth muscle relaxation but are also involved in contraction of cardiac muscle.
SMOOTH MUSCLE
- Sympathetic nerve synthesises and releases noradrenaline which binds to the β2 adrenoreceptor
- β2 adrenoreceptor is linked to a Gαs subunit, so it stimulates adenylate cyclase
- Increased conversion of ATP to cAMP
- Increased activation of protein kinase A
- Increased potassium ion channel activity
- Action of myosin light chain kinase is inhibited by protein kinase A due to phosphorylation of MLCK enzymes (regardless of any increase in [Ca 2+]
- Reduced phosphorylation of myosin light chains
- Reduced smooth muscle contraction
CARDIAC MUSCLE
- Sympathetic nerves synthesize and release noradrenaline which binds to the β1 adrenoreceptor
- The β1 adrenoreceptor is linked to a Gαs subunit, so it stimulates adenylate cyclase.
- This leads to an increase in intracellular cAMP concentration, due to increased conversion of ATP to cAMP which leads to an increase in activated PKA.
- Muscle contraction is increased i.e the contractions of the heart are much more forceful
Both adrenoreceptors are Gαs linked. The main difference is because MLCK enzymes are not present in cardiac muscles and therefore cardiac contraction is unaffected (as unlike smooth muscle, it is not dependent on the activity of this enzyme).
