VL 41 (Salim Seyfried)

Question 1

Molecular organization of the sacromere

Answer 1

• competent = cell that is able to respond to an inducing signal
• competence may be acquired during development by receptor expression/gap junction formation

Sliding filaments theory
says that Actin slide together during contraction
* H band visible in relaxed state
* Myosin activity pulls actin cables in middle → H band disappears (actin, myosin overlap), I band shortens (myosin moves closer to Z and)
* →every sarcomere with defined distance to which it can shorten (Δx = H band, part of I band)
* several sarcomeres in myofiber (parallel) → calculate shortening of entire muscle fiber (multiply Δx for each sarcomere, sarcomere number N)

Zband
* e- dense with various proteins (join adjacent sarcomeres; organize sarcomere set up, regulate activity)
* end points of one sarcomere
* Titin: defines spacing + set up of actin/myosin filaments; kinase activity; contains phosphorylation sites

based on structure-appearance under polarisation microscope
* I (isotropic) band: actin; light region
* A (anisotropic) band: myosin, actin; dark region
H band:
* myosin; middle region (light, lighter, dark)

Actin
* 6 actin filaments surround 1 myosin filament
* (+)-end towards Z band; (-)-end towards middle

Myosin
* (-)→(+)
* →pull actin filaments in middle

Question 2

The actin-myosin contractile cycle

Answer 2

• Rigor mortis due to myosin-binding to actin (rigor-complex); no ATP → stiff muscles
• separation (myosin-actin) by ATP
• ATP-binding → F-actin exchange; transition state with myosin in original conformation
• ATP-cleavage by ATPase → conformational change (37 nm to next actin monomer); unstable complex
• ADP, Pi-cleavage → conformational change → force (37 nm actin movement)
  ➔ Cycle occurs as long as ATP is available

Question 3

Relationship sacromere length/ force generation

Answer 3

• 3.6: sarcomere overstretching; few myosin head domains bound to actin→min. force
• 2.4: many head domains interact with actin→max. force
• 1.8: all head domains interact with actin; opposite directions/polarity→myosin pushes
  against each other; middle force

Question 4

Actin-Troponin-Tropomyosin complex

Answer 4

• Ca2+-binding to TnC (4 binding sites; all binding sites bound
  → conformational change)
• Troponin-Tropomyosin-complex changes
  → actin myosin-binding sites demasked
• Myosin-ADP-Pi-complex binds actin
  → actomyosin-ATPase activation
• Myosin-ADP-Pi→ADP-Pi release → myosin conformational change → force

TnT = Tropomyosin-binding subunit
TnC = Ca2+-binding subunit
TnI = inhibitory subunit

Question 5

The human heart

Answer 5

• Left ventricle: larger, more muscular (presses blood in aorta)
• Right ventricle: support lung aorta → shorter circulatory loop
• Atrioventricular valve opens → blood flow into ventricles →
  ventricle pressure increases→ valves close→ aortic/pulmonary valve opens
• Blue: blood from vena cava from brain
• Red: blood from lungs (oxygenated) → brain, body

Question 6

The cardiac contractile cycle

Answer 6

• pressure → blood (can ́t be compressed) escapes into region with lower pressure → pressure gradient

Question 7

Action potentials pace maker cells

Answer 7

• K-permeability decreases (K+-effluxv→ resting potential) with time & Na-permeability (“funny current”; ) increases → instable resting potential → slow depolarisation (Na+-influx in pace maker cells; = pace maker potential)
• at threshold potential (-40 mV)
  → voltage-gated Ca2+-channels opens
  → Ca2+-influx depolarisation
  → 10-20 mV
  → voltage-gated K+-channel (K+-efflux) open
  → hyperpolarisation
  → voltage-gated Ca2+- channels closes
  → repolarisation
  → hyperpolarisation
• excitation transmission onto other cardiomyocytes in entire atrium via gap junctions
• all cardiomyocytes can generate an action potential
• pace maker cells are first cells, which generate an action potential
• longer action potential than in e.g. nerve cells

Question 8

Excitation transmission heart:

Answer 8

• sinus knot: pace maker cells → 1st action potential
• cardiomyocytes in atrium linked via gap junctions → systolic phase → contract → blood pushed through AVC valves
• cells in atrioventricular knot excited, activated by neighbouring cardiomyocytes → excitation through his-bundle, tawara-branches → ventricle tips (purkinje fibers cover cardiomyocytes) → cardiomyocytes in ventricles (linked via gap junctions) pushes excitation wave upwards
• delay from tip wave initiation → blood from tip → aorta, pulmonary aorty

Question 9

Pressure gradients within cardiovascular system:

Answer 9

• flow = volume movement = blood volume, passing through a defined diameter of vessels during a defined period of time
  ➔ net flow in high pressure region (e.g. aorta), low pressure region (e.g. veine) is equal
  ➔ blood amount pushed in aorta has to be equivalent to blood amount that flows in through vena cava

Question 10

Resistance within the cardiovascular system:

Answer 10

• r variable (dilation, constriction); L, eta fixed
• resistance to bllod flow increases
  o increasing L, eta o decreasing r

Question 11

Effect of radius on the resistance within the cardiovascular system:

Answer 11

Question 12

Volume flow within the
cardiovascular system

Answer 12

Question 13

Flow velocity within cardiovascular system

Answer 13

• Higher vessel diameter→lower v
• Arterioles
  –> control flow into small capillary networks
  –> dilation/constriction
  –> in junction with vascular smooth muscle cells

Question 14

The pressure gradient within the cardiovascular system:

Answer 14

• requirement for the flow movement: pressure gradient

Question 15

Liquid exchange within capillaries:

Answer 15

• Pkap: hydrostatic, blood pressure
  → pushes blood into interstitium
• PIF: interstitial fluid pressure
  → pushes liquid into capillary, neglectable
• πKap: blood solutes with colloid osmotic pressure
  → pushes blood into capillary
• πIF: interstitial colloid osmotic pressure
  → pushes liquid into interstitium
• → small net deficit (→ lymphatic system) of liquid lost from capillaries
• blue: internal capillary pressure
• green: colloid osmotic pressure in capillary; contributes less to H2O-regain
  compared to liquid loss due to capillary pressure (red arrows indicate deficit)
• venous capillaries: capillary pressure with larger contribution for H2O-regain
• blood pressure drives liquids out of capillaries (filtration)
• ~ 90% resorbed back due to colloid osmotic pressure differences
• ~ 10% returned to circulation via lymphatics