CVS - contractile mechanisms

Question 1

Structure of a sarcomere

Answer 1

Thick filament = myosin + light chains

Thin filament = actin + tropomysin + 3 subunits of troponin (Tp1, TpT, TpC).

Question 2

Movement

Answer 2

Calcium binds to TpC to trigger movement of tropomysin and allow actin to interact with myosin.

Question 3

Length-tension relationship

Answer 3

The relationship between calcium and tension is a sigmoid relationship.
Approx the same shape in cardiac and skeletal muscle.
Ascending phase steeper in cardiac muscle than in skeletal muscle. This is due to differing intracellular calcium concentration and the longer sarcomere contractile proteins being more sensitive to calcium.
Intracellular Calcium concentration during contraction is 10um in skeletal muscle, 1um in cardiac muscle.
Length-tension relationship underlies increased twitch amplitude when cardiac muscle is stretched.

Question 4

Heartbeat

Answer 4

Transient low levels of calcium

Tetany in skeletal muscle caused by sustained high calcium levels.

Question 5

Starlings law of the heart

Answer 5

Increasing ventricular volume (venous return), increases the force of contraction to expel the additional blood.

Question 6

Starling curves of the heart

Answer 6

Vary ventricular volume and measure the stroke volume. Increased filling pressure of the ventricle (same as increased end diastolic pressure) increases the stroke volume of the heart.

Question 7

Guytons analysis

Answer 7

Matching venous return to cardiac output.
As cardiac output is increased, right atrial pressure decreases.
Right atrial pressure represents a back pressure, restricting venous return, assosciated with venous recoil.
Cardiac output intersects venous return when flow into veins equals flow out of heart.
In heart failure heart muscle is weakened, the jntersection occurs higher up the curve (higher venous pressure, larger ventricular volume).
Normal venous flow is high with low central venous pressure, and zero with high central venous pressure.
Normal cardiac output is low with low central venous pressure, and high with high central venous pressure.

Question 8

Skeletal muscle contraction

Answer 8

Caused by electrical signalling in the motor nerve which synapses with each muscle cell at a neuromuscular junction. ACh released by the nerve terminal diffuses across the synaptic cleft binds to and causes depolarisation of skeletal muscle membrane, this generates an action potential the causes contraction.
AP generated is propogated along the sarcolemma and down t-tubules. AP triggers calcium release from terminal cisternae of the SR. Calcium binds to troponin, troponin changes shape, removing the blocking action of tropomysin, exposing actin active sites.
Myosin crossbridges alternatively attach to actin and detach, this pulls actin filament towards the centre of the sarcomere, it is powered by ATP hydrolysis.
Removal of calcium by reuptake into the SR occurs after AP ends. Tropomysin blockage is restored, contraction ends, muscle fibres relax.

Question 9

Smooth muscle (vascular, respiratory,intestinal, urerogenital tract) contraction

Answer 9

Contractile proteins - myosin + light chains, actin, calmodulin, myosin light chain kinase, myosin light chain phosphatase.
A thick filament regulated system.
Calcium bound calmodulin displaces the auto-inhibitory region of myosin light chain kinase, which then phosphorylates myosin, now myosin is active and act with actin to cause contraction. Myosin light chain phosphatase catalyses dephosphorylation of myosin, causing relaxation.

Question 10

Flagella and cilia contractile mechanisms

Answer 10

Similat motility systems to bacteria, 9 + 2 microtubule arrangement.
Common motility unit in both cilia and flagella - axoneme
Structure of microtubule - 13 protofilaments, tubule A shares 3 protofilaments with tubule B. Tubules are linked around their circumference by protein nexin. Dyenein (equiv to myosin) binds to each tubulin and has a cross bridge like action, sproke protein joins outer tubules to inner pair.
9+2 arrangement only applies to motile section.
Dyenein proteins slide microtubules relative to each other, bjnding is created by the combination of sections that slide and sections that have fixed geometry.
Electrical activity of the cell and local concentration of cAMP and cGMP thought to be involved. Calcium levels next to microtubules, modulate activity.