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Cell Physiology & Pharmacology > Calcium & G-coupled Receptors > Flashcards

Calcium & G-coupled Receptors Flashcards

1
Q

In regards to the movement of ions, how an Na+ K+ ATPase functions?

A

3 Na+ ions out, 2 K+ ions in

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2
Q

Describe, in simple terms, the structure of PKA.

A

A combination of 4 subunits - 2 r subunits to which cAMP binds, and 2 c subunits which are the catalytic entity

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3
Q

List 3 ion transporters used to remove Ca2+ from the cell. Are these ion transporters passive or active transporters?

A

Plasma membrane Ca2+ ATPase (PMCA) - active
Smooth Endoplasmic Reticulum Ca2+ ATPase (SERCA) - active
Na+ Ca2+ Exchanger (NCX) - passive (antiporter)

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4
Q

What effect do agonists have on a receptor? In that case, what effect do antagonists have on a receptor?

A

Agonists activate a receptor - antagonists do not activate a receptor

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5
Q

Describe the structure of a G-protein coupled receptor?

A

A single polypeptide chain spanning the membrane 7 times - it has an extracellular N-terminus and an intracellular C-terminus

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6
Q

Describe the steps explaining how a substrate may activate a G protein.

A

The substrate binds the G protein-coupled receptor at either the N-terminus or by burying itself in the membrane of the receptor - this causes a conformational change in the receptor which releases the G protein - this causes the G protein to release GDP and bind GTP

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7
Q

What type of G-protein activates phospholipase C? What does phospholipase C catalyse?

A

Phospholipase C is actives by a Gq-type G-protein, and catalysts the cleavage of PIP2 to IP3 and DAG

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8
Q

What type of G-protein activates adenylyl cyclase? What type inhibits it?

A

Adenylyl cyclase is activated by Gs-type G-proteins, and is inhibited by Gi-type G-proteins

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9
Q

What molecules make up a G-protein?

A

A G-protein contains an alpha, beta, and gamma subunit (is heterotrimeric) - the beta and gamma subunits functionally act as one however

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10
Q

What cation is required for neurotransmitter release?

A

Ca2+ entry

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11
Q

What is the neuromuscular junction?

A

The synapse between a nerve and a skeletal muscle fibre (cell)

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12
Q

Are Ca2+ levels higher intracellularly or extracellularly?

A

Extracellularly

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13
Q

What is needed to increase the amount of Ca2+ entry at a nerve terminal?

A

Increase in frequency (as opposed to amplitude) of action potentials

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14
Q

What is the pore-forming subunit of a voltage-gated Ca2+ channel?

A

A1 (alpha 1) subunit

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15
Q

How many subunits does a voltage-gated Ca2+’channel have? How does this relate to a voltage-gated Na+ channel?

A

Both have 4 subunits, and share a very similar structure

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16
Q

What molecules can block L-type Ca2+ channels? Can you give 1 example?

A

DHP (dihydropyridines) e.g. nifedipine

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17
Q

What type,of Ca2+ channels are found in the heart?

A

R-type and T-type

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18
Q

How does increased intracellular Ca2+ affect Ca2+ channels?

A

Increased intracellular Ca2+ channels block the activity of Ca2+ channels

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19
Q

How do voltage-gated Ca2+ channels act in comparison to voltage-gated Na+ channels?

A

They act in a slower manner

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20
Q

What type of Ca2+ channels are found in skeletal muscle?

A

L-type

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21
Q

What breaks down acetylcholine in the synaptic cleft?

A

Acetylcholinesterase

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22
Q

What molecule brings Ca2+ vesicles to the pre-synaptic member ae to be released?

A

Synaptotagmin

23
Q

What complex is associated with fusion of the Ca2+ vehicle to form a pore in the pre-synaptic membrane?

A

The SNARE complex

24
Q

What molecules does a nicotinic acetylcholine receptor let pass through its pore?

A

Na+ and K+

25
Q

How many molecules of acetylcholine are required to induce a conformational change and open a nicotinic acetylcholine receptor?

A

2 molecules of acetylcholine

26
Q

If a nicotinic acetylcholine receptor lets through both Na+ and K+, which does Na+ flood into the cell and not K+?

A

The resting membrane potential of a cell is much closer to the equilibrium potential of K+ - as it is much further from the equilibrium potential of Na+, Na+ floods into the cell in an effort to reach equilibrium, which leads to depolarisation of the cell

27
Q

State an example of a competitive nicotinic acetylcholine receptor blocker.

A

Tubocurarine

28
Q

How can a competitive blocker of a nicotinic acetylcholine receptor (such as tubocurarine) be overcome?

A

Increasing the amount of acetylcholine (or the receptors endogenous substrate)

29
Q

How do depolarising blockers act at nicotinic acetylcholine receptors?

A

They act to keep nicotinic acetylcholine receptors in a depolarised state, thereby deactivating adjacent Na+ channels meaning an action potential cannot propagate

30
Q

Can you list an example of a depolarising nicotinic acetylcholine receptor blocker?

A

Succinylcholine

31
Q

Explain the pathogenesis of myasthenia gravis.

A

Myasthenia gravis is an autoimmune disorder where antibodies attack nicotinic acetylcholine receptors on skeletal muscle - these inactivated nicotinic acetylcholine receptors lead to a reduced amplitude of end-plate action potentials, leading to muscle weakness and fatigue

32
Q

How to nicotinic acetylcholine receptors and muscarininc acetylcholine receptors differ? How does this relate to their response?

A

Muscarininc receptors a G protein-coupled receptors, while nicotinic receptors are ligand-gated receptors - muscarininc acetylcholine receptors therefore act in a slower manner

33
Q

How does Ca2+ binding to a protein instigate a change in the proteins function?

A

Through a conformational change

34
Q

What are the approximate values of Ca2+ in the extracellular, cytoplasmic, and in the endoplasmic reticular compartments?

A
  • extracellular = 1-2x10^-3 M
  • cytoplasmic = 1x10^-7
  • endoplasmic reticulum = 2-3x10^-4 M
35
Q

List 3 transporters that are used in removing Ca2+ from the intracellular compartment of the cell.

A
  • NCX - Na+ Ca2+ exchanger
  • PMCA - plasma membrane Ca2+ ATPase
  • SERCA - smooth endoplasmic reticulum Ca2+ ATPase
36
Q

What receptors instigate Ca2+ induced Ca2+ release?

A

Ryanodine receptors - these are found in the membrane of the ER, and act to further increase Ca2+ concentrations in the cytosol, as a result of an increase in the cytosolic Ca2+

37
Q

How may activation of G protein-coupled receptors in the cell membrane lead to an influx of intracellular Ca2+?

A

Gq proteins activates phospholipase C which goes on to cleave PIP2 into IP3 and DAG - IP3 then binds IP3 receptors on the membrane of the ER, which leads to efflux of Ca2+ from the ER into the cytoplasm

38
Q

In normal muscle activity, when stimulation to contract stops, how are resting levels of Ca2+ regained?

A

The SER ATPase pump pumps Ca2+ back into the cell

39
Q

Briefly outline how calcium buffers act to regulate cytosolic Ca2+ following increased levels in the cytoplasm.

A

Ca2+ buffers can bind up to 50 Ca2+ ions, reducing the spread of Ca2+ current from a channel, meaning it acts less on its effectors

40
Q

List a Ca2+ buffer found in the cytosol, sarcoplasmic reticulum, and endoplasmic reticulum.

A
  • cytosol - parvalbumin
  • SR - calsequestrin
  • SER - calreticulin
41
Q

Describe the role of a Ca2+ sensor/trigger protein.

A

The Ca2+ sensor/trigger protein acts as an intermediate, binding Ca2+ and mediating its effects by then acting on its targets proteins itself

42
Q

Give an example of a Ca2+ sensor/trigger protein, briefly describing how it acts, and why this is important.

A

Calmodulin - this binds 4 Ca2+ ions, which induces a conformational change in calmodulin - this is important, as many of the Ca2+ targets can’t actually bind Ca2+ themselves

43
Q

Give a specific molecule that calmodulin acts on, and how it affects its activity.

A

Calmodulin can directly affect the activity of the PMCA (plasma membrane Ca2+ ATPase), increasing its sensitivity to Ca2+ when calmodulin is bound

44
Q

How many subunits make up a G protein? What is interesting about their arrangement?

A

3 - an alpha, beta, and gamma subunit - the alpha subunit acts in dependent lay, while the beta and gamma subunits act together

45
Q

What molecule binds a G protein to induce its active state?

A

GTP

46
Q

How is a G protein turned off?

A

The alpha subunit of a G protein contains intrinsic GTPase activity, which hydrolyses GTP to GDP, and switches off the G protein

47
Q

What is the second messenger of adenyl cylase? What is the secondary messenger of phospholipase C?

A
  • adenyl cyclase - cAMP

- phospholipase C - IP3/DAG

48
Q

Which molecule does cAMP binding regulate?

A

Protein kinase A

49
Q

What happens in Gi activation?

A

The G protein would not release GDP and bind GTP, so would not be activated, and you would get no adenyl cyclase, cAMP, or protein kinase A activity

50
Q

What molecule does adenyl cyclase act on to produce cAMP?

A

ATP

51
Q

Why is signal amplification so widely used in the body?

A

Good economic use of a few ligands to produce a much greater response

52
Q

What is ionotropy?

A

The force of muscle contraction

53
Q

What type of receptor is a u-opioid receptor?

A

A G protein-linked receptor

Cell Physiology & Pharmacology (5 decks)

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