Contractile Mechanism

Question 1

What are the three different types of muscles?

Answer 1

• skeletal
• cardiac
• smooth

Question 2

What is the purpose of the T-tubule?

Answer 2

The T-tubule bring membrane events deep within the cell for regulation.

Question 3

Describe skeletal muscle contraction.

Answer 3

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 Ca2+ down the T-Tubule.
The depolarisation 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 open the ryanodine receptors, releasing calcium ions into the sarcoplasm.
These calcium ions bind to Troponin(-C?) in the sarcoplasm, making Ca-Troponin, which leads to contraction.
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.

Question 4

Describe cardiac muscle contraction.

Answer 4

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 Ca2+ down the T-Tubule.
In this case, the DHP receptors are not in physical contact with the SR, so they simply release some calcium ions into the sarcoplasm. This causes the calcium release channels on the SR to open in response to the 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.
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.

Question 5

Describe smooth muscle contraction.

Answer 5

Adrenaline binds to a G-protein coupled receptor on the cell membrane, which, after a series of events, creates IP3. This IP3 travels down to the calcium release channels on the SR, and cause them to release Ca2+ ions into the sarcoplasm.
Calcium ions also enter the sarcoplasm from the ECF (extracellular fluid) via voltage-dependent or voltage-independent calcium channels.
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.

Question 6

Describe the generalised contractile cycle.

Answer 6

1) Ca2+ ions bind to troponin-C, weakening the bond between troponin and tropomyosin.
2) The troponin molecule changes position, rolling the tropomyosin molecule away from active sites on actin allowing interaction with primed myosin heads (has ATP).
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 acitn further up).
4) Myosin heads pivot towards the M line, releasing ADP. This action is known as a power stroke. This causes actin to slide along the myosin.
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.

Question 7

Describe the difference between smooth muscle and other muscle.

Answer 7

• the contractile arrays are NOT in regular arrays (instead, they are in a lattice-like array)
• the myosin contains a regulatory light chain
• there is low inherent ATPase activity
• the actin is longer than in skeletal muscle
• there is no troponin, but caldesmon and calponin instead
• the myofilaments connect with dense bodies
• there’s dual regulation (with MLCK (Myosin Light-Chain Kinase) and MLP)

Question 8

Describe what happens after the activation of Myosin-Light-Chain Kinase.

Answer 8

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.

Question 9

Describe the difference in performance between smooth and skeletal muscle.

Answer 9

• 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)
• there’s sustained contraction (latch state) due to dephosphorylated actin/myosin having low ATP affinity
• there’s a greater force generation in smooth muscle

Question 10

What is Rigor Mortis?

Answer 10

Dying cells release Ca ions, which allows the binding of A and M. However there is no more ATP for unbinding, so muscles stay contracted.