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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)?

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
What is the onset time of Malignant Hyperthermia?
Occur in minutes or hours
26
What is the gene responsible for Malignant Hyperthermia?
RyR1 gene on chromosome 19
27
What do RyR1 gene mutations cause in the cell?
Uncontrolled release of Ca2+ from the SR
28
What is a treatment for Malignant Hyperthermia?
Dantrolene (muscle relaxant)
29
What TWO ways can some proteins act as effectors for Ca2+?
1. DIRECTLY - Structrual / functional changes of Ca2+ binding proteins (e.g. Calmodulin) 2. INDIRECTLY - Effector activity modulated indirectly by Ca2+
30
What is Calmodulin?
A protein which **binds calcium** and **regulates the structure and function** of other proteins
31
Which domains on Calmodulin bind Ca2+?
* EF-hand * C2
32
How many binding sites does Calmodulin have?
Four (EF-hands)
33
What happens to Calmodulin after binding Ca2+?
Undergoes **conformational change** from 'dumbbell' structure to a compact spherical form
34
Which proteins does Calmodulin target?
* **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
What protein does Calmodulin-Dependent Protein Kinase II (CaMKII) phosphorylate to stimulate the release of neurotransmitters?
Synapsin 1
36
Which membrane trafficking machinery are phosphorylated by CaMKII?
* SNAREs * Rabs * ARF proteins
37
How does CaMKII activate neurotransmitter synthesis?
Phosphorylates and stimulates **tyrosine and tryptophan hydroxylases** which are involved in the synthesis of **catecholamines and serotonin**
38
What is the function of CaMKII in heart muscle?
Stimulates calcium sequestration
39
How does CaMKII work in heart muscle?
**Phosphorylates phospholamban**, a protein that **regulates activity of Ca2+ ATPase pumps** involved in the uptake of Ca2+
40
Which diseases has misregulation of CaMKII been linked to?
* Alzheimer's Disease * Angelman's Syndrome * Heart Arryhthmia
41
What is Calcineurin?
Serine/Threonine Protein Phosphatase
42
Is Calcineurin Ca2+ dependent or independent?
Ca2+ dependent
43
What are the TWO subunits of Calcineurin?
* A subunit (CATALYTIC) * B subunit (REGULATORY)
44
What does Calcineurin target?
PKA

BC3004: Cell Signalling (18 decks)

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