6.1

Question 1

What is the definition of blood pressure?

Answer 1

Blood pressure is the force that drives blood around the body.

Question 2

What does blood pressure do?

Answer 2

It pumps blood around the body.

Question 3

Does blood pressure remain constant?

Answer 3

No, it varies throughout the day and with other factors.

Question 4

What are the determinants of blood pressure?

Answer 4

Cardiac output, volume, and peripheral vascular resistance.

Question 5

How does heart rate affect blood pressure?

Answer 5

A faster, stronger heartbeat increases blood pressure.

Question 6

How does blood volume affect blood pressure?

Answer 6

In a closed system, increased volume raises blood pressure.

Question 7

What is peripheral vascular resistance affected by?

Answer 7

Compliance, vasoconstriction, and vasodilation.

Question 8

What happens to blood pressure during vasoconstriction?

Answer 8

It increases due to increased afterload and SVR (small lumen).

Question 9

What happens to blood pressure during vasodilation?

Answer 9

It decreases due to decreased afterload and SVR (large lumen).

Question 10

What determines vascular resistance?

Answer 10

The contractile state of blood vessels.

Question 11

What causes blood vessels to change?

Answer 11

Biochemical signals (Ang II, NA, ET-1) and biomechanical stimuli (flow/shear stress).

Question 12

Which cells are involved in vascular contractility?

Answer 12

Vascular smooth muscle cells (VSMC) and endothelial cells (EC).

Question 13

How do cytosolic Ca2+ levels affect vascular diameter?

Answer 13

↑ VSMC [Ca2+] causes contraction; ↑ EC [Ca2+] causes relaxation.

Question 14

What is the role of Ca2+ in VSMC in small arteries and arterioles?

Answer 14

It activates MLCK, leading to actin-myosin cross-bridge formation and contraction.

Question 15

Which pathways are involved in VSMC contraction?

Answer 15

Ca2+-calmodulin pathway and GPCR-mediated ROCK pathway.

Question 16

What does MLCK do?

Answer 16

Phosphorylates myosin regulatory light chains to initiate contraction.

Question 17

What does ROCK do in VSMC?

Answer 17

Activates myosin light chain phosphatase for contraction.

Question 18

What are the main calcium entry mechanisms?

Answer 18

Voltage-operated channels, receptor-operated channels, store-operated entry, purinergic receptors, transient receptor potential channels, and Na+/Ca2+ exchanger.

Question 19

Why is Ca2+ influx favoured into the cytosol?

Answer 19

Because cytosolic Ca2+ is lower than extracellular levels, creating a favourable gradient.

Question 20

What are VOCCs?

Answer 20

Voltage-operated Ca2+ channels.

Question 21

What are the three VOCC families?

Answer 21

Cav1, Cav2, and Cav3.

Question 22

What determines the gating properties of VOCCs?

Answer 22

The amino acid sequence of the pore-forming alpha-1 subunit.

Question 23

What do TM5-6, TM4, and TM6 do in VOCCs?

Answer 23

TM5-6 forms the pore; TM4 opens with depolarisation; TM6 binds calcium channel blockers.

Question 24

What are the two types of VOCCs and their activation ranges?

Answer 24

T-type (-60 mV to -15 mV) and L-type (-30 mV to +30 mV).

Question 25

What does Ca2+ entry through L-type and T-type channels cause?

Answer 25

VSMC contraction.

Question 26

What receptor does Ca3.2 activate?

Answer 26

Ryanodine receptor.

Question 27

What happens after Ca2+ is released from the VSM?

Answer 27

Activates Ca2+-activated K+ channels causing hyperpolarisation and inhibition of Ca1.2 and Ca3.1 channels.

Question 28

What activates receptor-operated Ca2+ channels?

Answer 28

Ligand binding to GPCR or TKR.

Question 29

What does phospholipase C activation lead to?

Answer 29

Increased IP3 and DAG → intracellular Ca2+ release and channel opening → VSMC contraction.

Question 30

What does store-operated calcium entry involve?

Answer 30

Calcium release from intracellular organelles and mobilisation from stores.

Question 31

What does increased IP3 activate?

Answer 31

IP3 receptors on the SR.

Question 32

What causes relaxation in VSMCs?

Answer 32

Ca2+ activates BKCa channels, SR Ca2+ uptake via SERCA, and hyperpolarisation.

Question 33

What are IP3Rs and how many isoforms exist?

Answer 33

Inositol trisphosphate receptors; 3 isoforms exist, but only 1 and 3 are in VSMC.

Question 34

What is needed to activate IP3Rs?

Answer 34

Binding of IP3 to all 4 subunits and Ca2+ binding.

Question 35

What is the biphasic effect of Ca2+ on IP3Rs?

Answer 35

Ca2+ can stimulate or inhibit depending on concentration.

Question 36

What is calcium-induced calcium release?

Answer 36

A mechanism where Ca2+ activates ryanodine receptors on the SR, causing more Ca2+ release.

Question 37

How many subunits do ryanodine receptors have?

Answer 37

Four subunits.

Question 38

What are calcium sparks?

Answer 38

Localised increases in Ca2+ causing relaxation via spatial interaction between RyRs and BKCa channels.

Question 39

What ensures BKCa activation during a calcium spark?

Answer 39

Spatial coupling and high local Ca2+ near spark foci (~20nm).

Question 40

What does SERCA do?

Answer 40

Pumps Ca2+ from the cytosol back into the SR, lowering cytosolic Ca2+.

Question 41

Which SERCA isoforms are predominant in VSMC?

Answer 41

SERCA2b > SERCA2a > SERCA3.

Question 42

What type of pump is SERCA?

Answer 42

A P-type ATPase.

Question 43

What are the conformational states of SERCA?

Answer 43

E1 (high Ca2+ affinity) and E2 (low Ca2+ affinity).

Question 44

What does each SERCA cycle require?

Answer 44

One ATP to pump two Ca2+ into the SR and release 2-3 H+ into the cytosol.