Session 5

Question 0

Why is there a high density of Ca2+ channels at nerve terminals?

Answer 0

Allows for Ca2+ influx to be significant enough for an AP to trigger release of neurotransmitter by exocytosis

Question 1

What are dihydropyridines?

Answer 1

Specific blockers of L type Ca2+ channels e.g. nifedipine

Question 2

What does an increase in intracellular calcium following an AP do?

Answer 2

Activates a group of proteins associated with the vesicle to promote exocytosis of ACh

Question 3

Describe neurotransmitter release

Answer 3

Ca2+ enters into the cell via Ca2+ channels
Ca2+ binds to synaptotagmin
Vesicle is brought close to the membrane
Snare complex make a fusion pore
Transmitter is released through this pore

Question 4

Describe the action of ACh

Answer 4

It binds to nicotinic ACh receptors on the post-junctional membrane to produce an end-plate potential. This depolarisation in turn raises the muscle about the threshold so that an AP is produced in the muscle membrane.

Question 5

What is myesthenia gravis?

Answer 5

Autoimmune disease targeting nACh receptors. Patients suffer profound weakness, which is exacerbated by exercise. Antibodies attack nAChR on post-synaptic membrane of skeletal muscles. Antibodies lead to a loss of functional nAChR by complement mediated lysis and receptor dehydration. Endplate potentials decrease in amplitude leading to muscle weakness and fatigue

Question 6

What are the two types of nAChR blockers?

Answer 6

Acetylcholine competitive antagonists such as tubocurarine which inhibit nicotinic receptors and depolarizing antagonists such as suxamethonium which acts as an acetylcholine excess.

Question 7

What can alterations in [Ca2+]i be useful for?

Answer 7

Fertilisation, proliferation, secretion, neurotransmission, metabolism, contraction, learning and memory, apoptosis and necrosis

Question 8

What is the value for [Ca2+]i in a resting cell?

What is the significance of this value?

Answer 8

100 nM
This is good because it means that changes in [Ca2+]i occur rapidly with little movement of Ca2+ but Ca2+ overload leads to loss of regulation and cell death

Question 9

What does the gradient of Ca2+ rely on?

Answer 9

Relative impermeability of the plasma membrane
Ability to expel Ca2+ across the membrane using Ca2+-ATPase and Na+-Ca2+ exchanger
Ca2+ buffers
Intracellular Ca2+ stores: rapidly releasable and non-rapidly releasable

Question 10

Describe the Ca2+-ATPase channel

Answer 10

Pumps Ca2+ out of the cell when the intracellular concentration increases. Ca2+ binds to calmodulin. The Ca2+-calmodulin binds to ATPase which is then removed.
Has a high affinity but a low capacity

Question 11

Describe the Na+/Ca2+ exchanger.

Answer 11

[Na+] gradient is used a driving force (requires Na+ K+ ATPase). Antiporter is electrogenic - should work to remove Ca2+ best at resting membrane potential.
Low affinity, high capacity

Question 12

What is the function of Ca2+ buffers?

Answer 12

Ca2+ buffers limit diffusion - ATP binding and Ca2+ binding proteins
Ca2+ ion diffuses 0.1-0.5 micro meters before encountering a binding molecule
Ca2+ diffusion depends on conc of binding molecules and their level of saturation

Question 13

What is a microdomain?

Answer 13

Areas where [Ca2+] is in excess of that measured globally

Question 14

How is Ca2+ brought in to cells?

Answer 14

Through voltage-operated Ca2+ channels (VOCC) and receptor operated ion channels (ionotropic receptors)

Question 15

How is calcium released from rapidly-releasable stores?

Answer 15

G-protein coupled receptors (GPCRs) and Ca2+ induced Ca2+ release (CICR –> ryanodine receptors)

Question 16

What is the rapidly releasable store of cells?

Answer 16

Mitochondria

Question 17

Give an example of calcium induced calcium released?

Answer 17

After membrane depolarisation Ca2+ enters through VOCCs, resulting in an explosive release of large amounts of Ca2+ from intracellular stores. This Ca2+ acts on ryanodine receptors of SR to drive Ca2+ release from intracellular stores. This explosive release causes a contractile event.

Question 18

How is Ca2+ handled by myocytes?

Answer 18

During the height of depolarisation the conditions favour reversal of Na+/Ca2+ exchanger. This results in a small amount of Ca2+ entry. As [Ca2+]i increases and membrane repolarisation starts, NCX reverts to Ca2+ extrusion to lower [Ca2+]i. Ca2+ is also pumped back in SR by SERCA.

Question 19

How do Ca2+ channels allow for long propogation?

Answer 19

They show voltage-sensitive activation and inactivation similar to Na+ channels but slower. This, along with low K+ conductance at depolarised AP allows prolongation of depolarisation in cardiac cells

Question 20

Give an example of the functional role of Ca2+ in contraction

Answer 20

In myocytes. Increase in cytoplasmic [Ca2+] results in contraction. Ca2+ binds to troponin, which undergoes a conformational change, causing tropomyosin to move and reveal binding sites on actin for the myosin head groups. In presence of ATP –> sliding filament model

Question 21

What is the role of mitochondria in calcium regulation?

Answer 21

It’s a uniporter with low affinity and high capacity.
Buffering of Ca2+
Regulate pattern and extent Ca2+ signalling
Stimulation of mitochondrial metabolism
Role in apoptotic cell death

Question 22

How are stores refilled?

Answer 22

Recycling of released cytosolic Ca2+ e.g. cardiac myocytes

Capacitative Ca2+ entry (store operated Ca2+ entry channel)

Question 23

Why is too much calcium a problem?

Answer 23

Can lead to activation of enzymes which can cause the cells to incur damage