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Flashcards in GPCRs/Calcium Deck (67):
1

What is the normal extracellular Ca2+ concentration?

1x10-3 M (1mM)

2

What is the normal intracellular Ca2+ concentration?

1x10-7 M (100nm)

3

What is the normal SER/SR Ca2+ concentration?

2-3x10-4 M (200-300 micromoles)

4

What channels cause the influx of Ca2+ into the cytosol from the extracellular fluid? (4)

VOCC
Ligand Gated ion Channels
Store operated ion channels

NCX (when cell is heavily depolarised)

5

What channels cause the efflux of Ca2+ from the cytosol out of the cell?

NCX
PMCA

6

Which molecules are moved by the NCX? How many of each?

3Na+ into the cell
1Ca2+ out of the cell

7

What provides the concentration gradient for the movement of Na+ and Ca2+ at the NCX?

Concentration gradient set up by the Na/K ATPase pump

8

Which channels can result in the efflux of Ca2+ from SER/SR stores?

Ryanodine Receptors (RyRs)
IP3 receptors

9

What type of GPCRs are activated to produce IP3 that can bind with IP3 receptors?

Galpha-q associated GPCRs

10

What acts as the ligand at RyRs? What is the process of efflux of Ca2+ at RyRs called?

Calcium ions

Calcium Induced Calcium Release

11

In which muscles is contraction driven by CICR?

Smooth muscle
Cardiac muscle

12

What is the main driver of Ca2+ release for contraction in skeletal muscle?

The T-tubule VOCCs are directly coupled with RyRs, so when VOCCs open, RyRs open

13

What proteins act to regulate Ca2+ cytosol concentrations and slows down diffusion of the ions within the cytoplasm?

Calcium ion buffer proteins

14

What is an example of a Ca2+ binding protein? Give an example of a protein it interacts with? How many calciums can it bind?

Calmodulin
Regulates activity of PMCA
Binds up to 4 calcium ions

15

What are the 3 superfamilies of cell surface receptor?

Kinase linked receptors (receptors with intrinsic enzymatic activity)

Ligand Gated ion Channels

G protein coupled receptors

16

Give an example of a ligand Gated ion channel. Give an example of a kinase linked receptor. Give an example of a GPCR.

Nicotinic ACh receptor

Insulin receptor

Muscarinic ACh receptor

17

What is affinity?

How well a ligand binds

18

What is efficacy?

How well a ligand causes a response

19

What is an agonist?

Molecule that binds to a receptor and activates it

20

What is an antagonist?

Molecule that binds to a receptor and does not activate it

21

Give two examples of B2-adrenoceptor agonists? Which disease are these drugs used in the treatment of?

Salbutamol
Salmeterol

Asthma

22

Give two examples of u-opioid receptor agonists? What are they used for?

Morphine, fentanyl

Analgesia/anaesthesia

23

Give two examples of b-adrenoceptor antagonists. What are they often used to treat?

Propranolol
Atenolol

Hypertension

24

Give two examples of d2-dopamine receptor antagonists. What are they used to treat?

Haloperidol
Sulpiride

Schizophrenia

25

GPCRs can respond to a small variety or great variety of stimuli?

A great variety of stimuli

26

GPCRs consist of how many polypeptide chains?

1

27

Why are GPCRs sometimes called 7TM receptors?

They have 7 transmembrane spanning regions

28

What is the position of the n terminal and c terminal at GPCRs?

Extracellular n terminal

Intracellular c terminal

29

What two places at GPCRs do ligands typically bind?

At a ligand binding site buried between the TM domains (made up by 2-3 of the domains)

At the n terminal region

30

What are two examples of ligands that bind between the TM domains at GPCRs?

Adrenaline
Acetylcholine

31

What are two examples of ligands that bind to GPCRs at the n terminal?

Glutamate
Thyroid stimulating hormone

32

What does binding of a ligand do to a GPCR?

Causes a conformational change in the GPCR - activating it and allowing it to interact with G proteins

33

What subunits make up a G protein?

Alpha

Beta & Gamma (Function together)

Make up a heterotrimer

34

What does interaction of the activated GPCR with the G protein result in?

GDP ----> GTP on the alpha subunit of the G protein

Immediate dissociation of the alpha subunit from the beta/gamma subunit

35

Why is GTP able to bind readily to the alpha sub unit once it is activated to?

GTP is present at high concentrations in the cell

36

What happens to the two separated units of the G protein to cause a response?

They each interact with effector proteins

37

Where in the cell do all the steps of G protein activation, termination etc occur?

On the plasma membrane

38

How is G protein signalling terminated?

GTP is hydrolysed to GDP

The alpha sub unit possesses GTPase activity and hydrolyses the GTP

High affinity between the two subunits returns, inactive G protein reformed

39

Which G proteins are all beta-adrenoceptors associated with? What is the enzymatic result of their activation?

G-alpha-S

Increased adeneylyl cyclase

40

What G proteins are the m4 muscarinic ACh receptors associated with? What is the enzymatic result of their activation?

G-alpha-i

Decreased adenylyl cyclase

41

On which GPCRs does pertussis toxin have its effect?

Gi GPCRs

42

What effect does Pertussis toxin have on the Gi protein?

Causes covalent modification
No GDP/GTP exchange

G proteins can't be activated

43

What G proteins are affected by cholera toxin?

Gs proteins

44

What effect does cholera toxin have on the G protein?

Makes the G protein unable to hydrolyse GTP

Permanently activated G protein

45

Which reaction does adenylyl cyclase catalyse?

ATP ----> Cyclic AMP

46

Which reaction does phospholipase C catalyse?

PIP2----> IP3 + DAG

47

What reaction does PI3K catalyse?

PIP2----> PIP3

48

What reaction does cGMP phosphodiesterase catalyse?

Cyclic GMP ---> 5'-GMP

49

What are examples of effectors at the ends of GPCR pathways?

Enzymes
Ion channels
VOCCs

50

Why is the cell not deprived of ATP during increased activity of adenylyl cyclase?

In reality it is a relatively small side reaction

51

What does cyclic AMP primarily bind to after it has been produced?

PKA

52

Name 2 GPCRs other than b-adrenoceptors that are Gs preferring.

D1-dopamine receptors
H2-histamine receptors

53

Name two examples of Gi preferring GPCRs other than a2, m2 and m4 receptors.

D2-dopamine receptors
u-opioid receptors

54

What is the structure of PKA?

Has 4 sub units

2 Regulatory
2 catalytic

55

How does cyclic AMP interact with PKA?

Cyclic AMP binds with the regulatory sub units of PKA

Release of catalytic sub units

56

What does PKA do?

Phosphorylate different substrates

57

Other than the pumps that exist, how else is the very low intracellular calcium ions concentration maintained?

Relative impermeability of the plasma membrane and calcium binding proteins

58

Which GPCRs result in increased phospholipase C activation?

Gq preferring GPCRs

59

What substrate does phospholipase C work on?

PIP2

Cleaves it to form IP3 and DAG

60

What does increased DAG production result in?

Activation of PKC

61

The activation of IP3 receptors can increase intracellular calcium ion concentration how many fold within a few seconds?

5-10 fold

62

Other than a1, m1 and m3 receptors, name a receptor that prefers Gq proteins?

H1-histamine receptors

63

Increased intropy is the result of activation of which receptors? How does it cause increased force of contraction?

B1-adrenoreceptors

PKA phosphorylates VOCCs, increased calcium ---> increased contraction

64

Vascular smooth muscle contraction (vasoconstriction) is controlled by which GPCR?

a1-adrenoceptors

65

Bronchoconstriction can be affected by which GPCR?

M3-muscarinic receptors

66

What is an example of an effector molecule for the activated beta/gamma subunit?

VOCCs

67

What effect can beta/gamma sub units have at VOCCs at synapses?

Inhibit specific VOCCs reducing calcium influx, reducing neurotransmitter release