Lecture 6 - Contractile mechanism

Question 1

Contraction

Answer 1

Interaction of actin and myosin fuelled by ATP and driven by a rise in Ca2+.

Question 2

Muscle function (4)

Answer 2

Movement of skeleton.
Movement of hollow organs.
Structure to hollow organs when under pressure.
(In)voluntary control of diff muscle over diff time scales.

Question 3

Two types of muscle in general (3)

Answer 3

Striated - skeletal/cardiac muscle
Smooth - blood vessels/ GI tract
Both provide contraction using two contractile proteins (actin and myosin) and regulatory protein (tropomyosin)

Question 4

Skeletal muscle (9)

Answer 4

Striated - cross striation = actin and myosin highly organised.
Voluntary- Controlled by motor nerves.
Muscle contracts in one direction.
Short length of contraction.
Made of bundles of muscle fibres enclosed with a plasma membrane (sarcolemma).
Sarcoplasmic reticulum extends through muscle fibre and contains calcium ions for muscle contraction.
Parts of sarcolemma fold inwards for transverse-tubules= spread electrical impulses so they contract at the same time.
Muscle fasciculus—> Muscle fibre —> Myofibril.
Fibres are tubular and multinucleated.

Question 5

Cardiac muscle (6)

Answer 5

Specialised striated - actin and myosin highly organised.
Striations can be seen but are fairer than skeletal muscle.
Involuntary.
Cells branch and interconnect (intercalated discs) resulting in simultaneous contraction and allows diffusion of ions between cells so AP pass easily and quickly.
Individual cells form long fibres, which branch to form cross-bridges between fibres = ensure electrical stimulation spreads evenly over the walls of chambers.
Fibres are branched and uninucleated.

Question 6

Smooth muscle (6)

Answer 6

Non-striated = no regular arrangement = actin and myosin are disorganised.
Involuntary SM controlled by ANS.
Contracts in different directions.
Slow contraction speed.
Can remain contracted for a long time.
Fibres are spindle shaped and uninucleated.

Question 7

Contractile organised apparatus in striated muscle (3)

Answer 7

Z band - attachment sites for actin
I band - Non-superimposed length of actin
A band - entire length of myosin

Question 8

What happens during sarcomere contraction (5)

Answer 8

Sarcomere - shortens
A-band - no change
I-band - shortens
H-zone - shortens
Z-line - no change

Question 9

What happens during sarcomere relaxation (5)

Answer 9

Sarcomere - lengthens
A-band - no change
I-band - lengthens
H-zone - lengthens 
Z-line - no change

Question 10

Actin (5)

Answer 10

Thinner filament = two strands twisted around each other.
G actin = globular protein, binds ATP = ATPase activity.
F actin = helical protein used ATP to make filaments.
Tropomyosin in striated (not SM), covers actin binding site at rest.
Actin also contains Troponin system e.g. TnI, TnC (calcium binding), TnT(tropomyosin binding).

Question 11

Myosin (7)

Answer 11

The thicker filament.
Myosin II found in muscle.
2 heavy chains - intertwined.
Forms HEAD domain.
ATP binding site, ATPase activity.
Binds to active actin binding sites.
4 light chains = 2 per head.

Question 12

T-tubules (2)

Answer 12

T tubules are cell membranes that extend into the cell interior.
Interact with the internal calcium store (sarcoplasmic reticulum).

Question 13

Model of Ca2+ ion regulation by the SR in the muscle

Answer 13

Depolarisation initiated by nAChRs maintained by sodium channels spreads deep into t-tubules. You find DHP (dihydropyridine) which physically interacts with a calcium release channel in SR (sarcoplasmic reticulum).

Question 14

Model of Ca2+ ion regulation by SR in skeletal muscle (3)

Answer 14

DHP protein is an ion channel that does not conduct ions.
Dihydropyridines = calcium channel blockers = therefore, does not conduct ions.
Physical interaction between DHP and RyR (Ryanodine receptors).

Question 15

How do actin and myosin interact to produce muscle contraction (7,2)

Answer 15

90 - 45 degrees motion. Rowing action.
Muscle is stimulated AP along SARCOLEMMA down T-TUBULE.
Into SR (sarcoplasmic reticulum), stimulates calcium ions channels to open and enter SARCOPLASM.
Calcium binds to TROPONIN-C, which alters the shape, pulling TROPOMYOSIN aside, exposing binding sites on actin.
Primed myosin heads (ATP) bind to actin forming actin-myosin cross bridges between filaments.
Ca2+ activate ATPase activity of MYOSIN (hydrolysis of ATP –> ADP + P).
Myosin head detaches from actin and attaches itself to another actin, the cycle is repeated.
Myosin head cycle 5x per second = 15 Microm s-1.
Once contraction occurs Ca2+ PUMPED back into SR, the muscle relaxes.

Question 16

Model of Ca2+ ion regulation by SR in cardiac muscle (3)

Answer 16

Not a physical interaction between a voltage sensing protein or an ion channel.
Calcium goes from t-tubule into the cell. Calcium-induced calcium released (CICR).
Calcium channel similar to DHP protein in skeletal muscle  - BUT IT ALLOWS IONS THROUGH. and is blocked by dihydropyridine drugs.
Ryanodine receptors form a class of intracellular calcium channels in various forms of excitable animal tissue e.g. muscle/neurons.

Question 17

Smooth muscle contraction (12)

Answer 17

Not in regular arrays.
No t-tubules, SR and IP3 receptor.
IP3 = Inositol trisphophosphate.
Less developed SR.
Myofilaments connect with dense bodies.
No troponin but CALDESMON and CALPONIN.

IP3 released by a receptor diffuses to a receptor, Calcium released.
Calcium sensor is CALMODULIN (not tropnonin). 4 Ca2+ = 1 CALMODULIN.
Activates a GO mechanism –> MLCK (Myosin Light Chain Kinase).
Latch state is the slow release of actin from the myosin.
Myosin in smooth muscle is a different isoform than the skeletal muscle (MYH11 vs MYH1).
Lower ATPase activity - does not relax as well.
MLCK [P] regulatory MLC at ser 19 = increases ATPase activity of myosin head x1000.

Question 18

Performance - Smooth muscle vs Skeletal muscle (5)

Answer 18

Greater shortening in smooth vs skeletal (longer actin).
Slower speed of contraction than skeletal muscle (x30)
Lower energy requirement in smooth muscle than skeletal - latch state.
Greater force of generation in smooth vs skeletal muscle.
Sustained contraction (latch state) due to de[P] actin/myosin having low ATP affinity - cross bridge NOT released.