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ICPP > 3 - G-Proteins + Calcium > Flashcards

3 - G-Proteins + Calcium Flashcards

1
Q

How can you turn off a G-Protein?

A

GTPase in alpha subunit. Prevents overreactive. Drugs and toxins can target GTPase

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2
Q

How would you describe a G-protein?

A
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3
Q

What is the main set up of a GPCR?

A
  1. A receptor (ligand bind in TMD or N terminal)
  2. G-protein
  3. Effector (enzyme/ion channel)
  4. Second messenger
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4
Q

What are the three types of G-protein and what do they govern?

A
  • Gs - Stimulate adenylate cyclase
  • Gi - Inhibit adenylate cyclase
  • Gq - Stimulate phospholipase C
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5
Q

What types of G-protein are all the main receptors?

A

M2 also salivary glands

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6
Q

What is the cascade pathway of a Gs protein?

A
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7
Q

What is the cascade pathway of a Gq protein?

A
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8
Q

How does a cholera and pertussis toxin work?

A

Pertussis - Gi protein. Covalently binds to alpha subunit and inhibits GDP exchange for GTP

Cholera - Prevents GTPase action so Gs-protein constantly activated, can lead to loss of Cl- from cells, leading to diarrheoa

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9
Q

What is the cascade pathway of a Gi protein?

A
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10
Q

How does Phospholipase C work?

A
  • Cuts PIP2, (membrane phospholipid), into DAG and IP3.
  • IP3: Water soluble so binds to LGIC on ER. Receptor stimulated and opens. Influx of calcium ions into cytosol
  • DAG: Lipid soluble. Activates PKC, which acts on lots of proteins
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11
Q

How does cyclic AMP activate PKA?

A

PKA has 4 subunits. cAMP binds to R subunits and releases C subunits so they are active

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12
Q

How does positive inotropy in the heart work?

A
  • B1 Adrenoreceptor therefore GS
  • Sympathetic adrenaline
  • PKA phosphorylates VOCC so that when there is wave of depolarisation, more Ca2+ enters the cell, more Ca2+ released from ER, more forceful contraction
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13
Q

What G protein is involved in smooth muscle contraction?

A

Q

  • Vasoconstriction - a1
  • Bronchoconstriction - M3
  • GI Tract - a2?
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14
Q

How does arteriolar vasoconstriction work?

A
  • Sympathetic noradrenaline on a1 receptors
  • IP3 produced which releases Ca2+ from ER, leading to contraction
  • DAG produced activates PKC which can activate proteins that sustain contraction
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15
Q

How do you modulate neurotransmitter release?

A
  • U-opiod Gi receptor
  • BY unit binds to VOCC stopping it from opening
  • Less Ca2+ in cell, therefore vesicles containing neurotransmitter cannot be released
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16
Q

Where are U-Opioid receptors found?

A

In presynaptic neurones

17
Q

How is chronotropy regulated in the heart?

A
  • M2 so Gi
  • Production of BY binds to K+ channels so membrane more permeable to K.
  • Slows polarisation of membrane as K is leaving
  • SA fires slower, negative chronotropy
18
Q

If opioids stop VOCC working, how does the heart keep contracting?

A

VOCC in neurones are a different type to in the heart.

Heart - L

Neurones - P/Q and N

19
Q

Why is signal amplification important?

A

Allows small changes in extracellular signals to cause significant changes in intracellular behaviour

20
Q

What are serum calcium levels?

A

8-10 mg/dL. 50% is free

21
Q

How is calcium homeostasis regulated?

A
  • Intestinal calcium uptake
  • Bone calcium regulation
  • Reabsorption in kidneys

ENDOCRINE CONTROL

22
Q

What is the concentration of calcium in different compartments?

A
23
Q

What hormones regulate calcium levels?

A
  • Calcitonin (thyroid)
  • Parathyroid hormone
  • Ca receptors in parathyroid gland
  • 1,25 Dihydroxyvitamin D3
24
Q

Why are calcium gradients important?

A
  • Muscle contraction
  • Fertilisation
  • Cell apoptosis
  • Neurotransmission
25
Q

How is calcium concentration increased in a cell?

A
  • LGIC
  • VOCC
  • IP3

- CICR (ryanodine receptor) (calcium binds to receptor opening it)

  • SOCC (low Ca in ER, ligand from ER binds to channel)
26
Q

How are calcium gradients set up in a cell?

A
  • NCX
  • PMCA
  • SERCA
27
Q

Why is NCX classed as active if it is using Na’s concentration gradient?

A

Na+/K+ ATPase is setting up concentration gradient of sodium actively

28
Q

What are the two responses in intracellular calcium concentration when a receptor is activated and why are there multiple responses?

A
  • Peak Plateau
  • Oscilliations

Some proteins need large amounts of calcium to be acitvated, some small and calcium increase may be within microdomains not across whole cell

29
Q

What G proteins does the pertussis toxin act on and why doesnt it affect GS?

A
  • Gi and Go
  • Doesn’t affect Gs as doesnt have same alpha subunit

ICPP (12 decks)

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