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BC3004: Cell Signalling > Calcium as a Secondary Messenger > Flashcards

Calcium as a Secondary Messenger Flashcards

1
Q

What are THREE functions of increased Ca2+?

A
  1. Exocytosis (e.g. neurotransmitter release)
  2. Muscle contraction
  3. Regulation of Ca2+ dependent kinases and phosphatases
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2
Q

Where are the TWO main Ca2+ stores in the cell?

A
  1. ER
  2. Mitochondria
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3
Q

What is the RESTING concentration of Ca2+ in the cell?

A

~100nM

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4
Q

What is the ACTIVE concentration of Ca2+ in the cell?

A

µM

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5
Q

What ion channels are involved in the influx of Ca2+ ions from the EXTRACELLULAR environment?

A
  • Voltage-operated Ca2+ channels (VOCCs)
  • Receptor-operated Ca2+ channels (ROCCs)
  • Secondary messenger-operated channels (SMOCCs)
  • Mechanically-operated Ca2+ channels (MOCCs)
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6
Q

How are Voltage-Operated Ca2+ Channels (VOCCs) opened?

A

Open in response to membrane depolarisation

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7
Q

How are Receptor-Operated Ca2+ Channels (ROCCs) opened?

A

Directly coupled to receptors at the cell-surface

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8
Q

How are Secondary Messenger-Operated Ca2+ Channels (VOCCs) opened?

A

Open in response to increases in the cytosolic concentration of secondary messengers

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9
Q

How are Mechanically-Operated Ca2+ Channels (VOCCs) opened?

A

Gated in response to mechanical stimulation of the cell

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10
Q

What TWO families of channel proteins are involved in the release of Ca2+ ions from INTRACELLULAR stores in the ER?

A
  1. IP3 Receptors
  2. Ryanodine Receptors (RyRs)
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11
Q

What are FIVE characteristics of IP3 receptors?

A
  1. Located in ER
  2. Expressed ubiquitously (most in brain)
  3. Activated by IP3 to release Ca2+ from ER
  4. Tetrameric structure
  5. Three isoforms
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12
Q

What are FOUR characteristics of IP3 receptors?

A
  1. Located in SR
  2. Sensitive to plant alkaloid Ryanodine
  3. Tetrameric structure
  4. Three isoforms
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13
Q

What is the mechanism by which IP3 Receptors and RyRs open?

A
  • Dependent on cytosolic Ca2+ concentration
  • Called Calcium Induced Calcium Release
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14
Q

What is required for complete opening of Ca2+ channels in terms of concentration?

A

Threshold concentration of free Ca2+ is required

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15
Q

What is the function of CICR?

A

Acts as amplification mechanism

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16
Q

What does CICR do when cytosolic Ca2+ is increased beyond a certain point?

A

Inhibits further opening of channels
* Negative Feedback

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17
Q

TRUE OR FALSE:
IP3 Receptors require IP3 to be activated

A

True
* Ca2+ acts as a co-activator (CICR)

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18
Q

Are RyRs directly or indirectly activated by Ca2+ (CICR)?

A

Directly

19
Q

What mechanical way can RyRs be activated?

A

Interaction with dihydropyridine receptors which act as ‘voltage-sensors’ in the plasma membrane

20
Q

What THREE ways can Ca2+ be removed from the cytosol?

A
  1. Ca2+ ATPases in the plasma membrane and on the ER and Mitochondria
  2. Association of Ca2+ with binding proteins which buffer it
  3. Ca2+ can also be bound to negatively charged phospholipids
21
Q

What are THREE ways that intracellular calcium can be measured?

A
  1. Calcium binding fluorescent dyes (Fluo-3, Fura-2)
  2. Calcium sensing proteins
  3. 45Ca2+ radiolabelled Ca2+
22
Q

What is Malignant Hyperthermia?

A

Inherited disorder of skeletal muscle

23
Q

What causes Malignant Hyperthermia?

A

Response to inhalation of anaesthetics such as halothane, succinylcholine

24
Q

What are the symptoms of Malignant Hyperthermia?

A
  • Increased O2 consumption and CO2 production
  • High increase in body temperature
  • Tachycardia
  • Skeletal muscle rigidity
  • Organ failure
25
Q

What is the onset time of Malignant Hyperthermia?

A

Occur in minutes or hours

26
Q

What is the gene responsible for Malignant Hyperthermia?

A

RyR1 gene on chromosome 19

27
Q

What do RyR1 gene mutations cause in the cell?

A

Uncontrolled release of Ca2+ from the SR

28
Q

What is a treatment for Malignant Hyperthermia?

A

Dantrolene (muscle relaxant)

29
Q

What TWO ways can some proteins act as effectors for Ca2+?

A
  1. DIRECTLY - Structrual / functional changes of Ca2+ binding proteins (e.g. Calmodulin)
  2. INDIRECTLY - Effector activity modulated indirectly by Ca2+
30
Q

What is Calmodulin?

A

A protein which binds calcium and regulates the structure and function of other proteins

31
Q

Which domains on Calmodulin bind Ca2+?

A
  • EF-hand
  • C2
32
Q

How many binding sites does Calmodulin have?

A

Four (EF-hands)

33
Q

What happens to Calmodulin after binding Ca2+?

A

Undergoes conformational change from ‘dumbbell’ structure to a compact spherical form

34
Q

Which proteins does Calmodulin target?

A
  • Protein Kinases (calmodulin-dependent protein kinase II, myosin light chain kinase)
  • Protein phosphatases (calcineurin)
  • Other enzymes (glycogen phosphorylase kinase)
  • Transporters (Ca2+ ATPase)
  • Ion Channels (RyR, IP3R)
35
Q

What protein does Calmodulin-Dependent Protein Kinase II (CaMKII) phosphorylate to stimulate the release of neurotransmitters?

A

Synapsin 1

36
Q

Which membrane trafficking machinery are phosphorylated by CaMKII?

A
  • SNAREs
  • Rabs
  • ARF proteins
37
Q

How does CaMKII activate neurotransmitter synthesis?

A

Phosphorylates and stimulates tyrosine and tryptophan hydroxylases which are involved in the synthesis of catecholamines and serotonin

38
Q

What is the function of CaMKII in heart muscle?

A

Stimulates calcium sequestration

39
Q

How does CaMKII work in heart muscle?

A

Phosphorylates phospholamban, a protein that regulates activity of Ca2+ ATPase pumps involved in the uptake of Ca2+

40
Q

Which diseases has misregulation of CaMKII been linked to?

A
  • Alzheimer’s Disease
  • Angelman’s Syndrome
  • Heart Arryhthmia
41
Q

What is Calcineurin?

A

Serine/Threonine Protein Phosphatase

42
Q

Is Calcineurin Ca2+ dependent or independent?

A

Ca2+ dependent

43
Q

What are the TWO subunits of Calcineurin?

A
  • A subunit (CATALYTIC)
  • B subunit (REGULATORY)
44
Q

What does Calcineurin target?

A

PKA

BC3004: Cell Signalling (18 decks)

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