MR S5 - Control of Calcium

Question 0

Discuss the diversity of Ca channels

Answer 0

Ca channels have structural diversity
This means a blocker of one channel may not block another channel
They also have different primary locations
This means if one channel is selectively blocked, there can be a localised effect

Question 1

Describe the sequence of events when an action potential reaches the presynaptic membrane

Answer 1

Arrival of AP causes Ca channels to open
Influx of Ca ions down concentration gradient
Increase of intracellular Ca concentration causes neurotransmitter release

Question 2

How does fast synaptic transmission occur?

Answer 2

In fast synaptic transmission, the receptor protein is also the ion channel - this means no secondary messenger is necessary

Question 3

Describe in detail how intracellular Ca concentration causes ACh release

Answer 3

Ca ions enter cell
Bind to “synaptotagmin”, causing snare complex formation
Snare complex causes ACh release

Question 4

What occurs on the post junctional membrane after ACh release from presynaptic neurone?

Answer 4

The ACh will bind to the nicotinic ACh receptors on the post-junctional membrane
Depolarisation raises the muscle to threshold
End plate potential produced

Question 5

State the binding site of competitive nicotinic receptor blockers and give an example of a blocker

Answer 5

Bind at the ACh binding site

Eg tubocurarine

Question 6

Describe how depolarising nicotinic receptor blockers work and give an example of a blocker

Answer 6

Cause maintained depolarisation at the post junctional membrane
Therefore Na channels do not activate due to accommodation
Eg succinylcholine (used in operations to induce paralysis)

Question 7

Describe myasthenia gravis

Answer 7

Antibodies destroy ACh receptors on post synaptic membranes
Causes drooping eyelids, profound weakness which worsens upon exertion
Treated with AChe inhibitors

Question 8

Why is control of intracellular Ca concentration important?

Answer 8

So many processes use small changes in Ca concentration as triggers or use Ca as a catalyst
Ca cannot be metabolised, can only be moved in or out of the cell

Question 9

What are the benefits and disadvantages of very tightly controlled intracellular Ca concentration

Answer 9

Benefits:
-Changes in concentration can occur rapidly and without active transport
Disadvantages:
-Energy expensive to maintain
-Ca overload causes loss of regulation and cell death

Question 10

What does the Ca gradient rely on?

Answer 10

• The impermeability of the membrane
• The ability to expel Ca
• Ca buffers
• Intracellular Ca stores

Question 11

How is membrane permeability controlled?

Answer 11

By the presence of ion channels and their status (open/closed, active/inactive)

Question 12

How may Ca be expelled from the cell?

Answer 12

By Ca ATPase:
High affinity, low capacity
Intracellular Ca binds to calmodulin then this complex bonds to the channel and Ca is removed from the cell
By Na Ca exchanger
Low affinity, high capacity
Na gradient used as driving force (3Na in, 1Ca out)
Electrogenic and works best at resting membrane potential

Question 13

How do Ca buffers affect the Ca gradient?

Answer 13

Buffers limit diffusion via binding proteins eg parvalbumin, calreticulin, calsequestin, calbindin
Diffusion depends on binding protein concentration and saturation

Question 14

How may intracellular Ca be increased?

Answer 14

Ca influx through plasma membrane (altered permeability)
Ca release from rapidly releasable stores
Ca release from non rapidly releasable stores

Question 15

How does Ca enter the cell via the plasma membrane?

Answer 15

Voltage gated calcium channels open to allow an influx of Ca down it’s concentration gradient
Receptor operated Ca channels open in response to binding of ligands

Question 16

What are the rapidly releasable Ca stores?

Answer 16

There is a store in the sarcoplasmic reticulum which is set up by the SERCA membrane protein
Ca binds to calsequestrin

Question 17

How is Ca released from rapidly releasable stores?

Answer 17

G protein coupled receptors (GPCRs)

Calcium induced calcium release (CICR)

Question 18

How do GPCRs cause Ca to be real eased from rapidly releasable stores?

Answer 18

A ligand binds to the GPCR on the cell membrane
Activates a subunit which binds to membrane phospholipid PIP2
Release of IP3 which binds to a receptor on the sarcoplasmic reticulum
Triggers the release of Ca down it’s concentration gradient

Question 19

How does CICR or “Ca induced Ca release” cause Ca to be real eased from rapidly releasable stores?

Answer 19

Ca binds to Ryanodine receptor on sarcoplasmic membrane

This triggers the release of Ca down it’s concentration gradient

Question 20

When is CICRs role especially important physiologically?

Answer 20

In cardiac myocytes, the CICR mechanism is responsible for 85% of the Ca released so is very important for strong contraction of cardiac muscle

Question 22

Why is Ca concentration returned to basal levels?

Answer 22

Repetative signalling requires a return to basal levels

Too high intracellular [Ca] for too long is toxic to cells

Question 23

How are Ca stores refilled?

Answer 23

Recycling of cytosolic Ca

SOC (store operated Ca channel) moves mitochondrial Ca to the sarcoplasm

Question 24

What does a return to basal levels of Ca require?

Answer 24

Termination of signal
Ca removal
Ca store refilling

Question 25

Describe muscarinic receptors

Answer 25

G protein coupled receptors
Slower than nicotinic
Acts by secondary messengers (multiple subunits)

Question 26

Describe nicotinic receptors

Answer 26

Ca influx causes release of ACh at presynaptic membrane
ACh binds to a nicotinic receptor on the post synaptic membrane
The receptor is also a Na channel which opens and allows an influx of Na which causes depolarisation
This is fast.

Question 27

How is Ca released from non rapidly releasable stores?

Answer 27

Mitochondria actively take up Ca to aid buffering, regulatory signalling (micro domains) and stimulation of ATP production via a Ca uni porter
Ca is also taken up as an emergency response when cytoplasmic Ca is high