Control Of Cytosolic Calcium Flashcards

1
Q

Name some functions of calcium

A
Apoptosis 
Muscle contraction
Neurotransmission
Gene regulation
Memory (LTP)
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2
Q

Equilibrium potential of calcium?

A

+123mv

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3
Q

What are the intracellular and extracellular conc of calcium?

A
Intra = 10^-7M
Extra = 1-2mM
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4
Q

What are the advantages of a large calcium gradient?

A

Small influx = large conc difference

Little has to be removed to re establish resting calcium

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5
Q

Disadvantages of large calcium gradient?

A

maintaining gradient is energy expensive

Easy to overload and lead to cell death

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6
Q

How is the calcium gradient set up and maintained?

A

Plasma membrane Ca2+ ATPase
NCX
Calcium buffers

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7
Q

What are come characteristic of the PMCA?

A

High affinity, low capacitance
Therefore works when levels of calcium are low and does not shift large amounts
Uses ATP
Also regulated by calcium calmodulin complex. Increase in calcium increase complex binding to PMCA which stimulates it to remove calcium

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8
Q

What direction does the PMCA move calcium?

A

Extracellularly

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9
Q

What direction does the NCX move ions?

A

RMP = 3Na+ in 1Ca2+ out

Depolarisation reverses this

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10
Q

Where are some characteristics of NCX channels?

A

Powered by secondary activity transport by sodium gradient set up by Na+K+ATPase
High capacity low affinity
Channel is electrogenic (net + influx) means sodium harder to move in at more positive mV

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11
Q

Name some calcium buffers?

A

Calsequestrin
Parvalbumin
Calbindin

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12
Q

What do calcium buffers do?

A

Bind to calcium with no intrinsic function to slow down rise in intracellular calcium and prevent global cellular rise by maintaining calcium rise in micro-domain (within 0.1-05(micro)m)

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13
Q

What are calcium trigger proteins?

A

Bind calcium which causes an altered effect on protein

E.g. Synaptotagmin in neurotransmission

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14
Q

Explain synaptotagmins (ST) role in neurotransmission

A

ST is a V-SNARE which has a C2A and C2B domain on the cytosolic side
These bind calcium (C2a = 3 calcium, C2B = 2 calcium)
Calcium bind here follows VGCC opening which causes conformational change which allows it to interact with syntaxin (t-SNARE)
Allows for fusion

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15
Q

How is elevation of intracellular calcium achieved?

A

VOCC
Ionotropic glutamate receptors
GPCRs coupled to Gq
Calcium induced calcium release

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16
Q

What are some characteristics of VGCC?

A

Many types (N,L,P/Q,R)
Modulated by PKC
Alpha 1 subunit = 6TMDs made of 4 connected domains
May have accessory subunits

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17
Q

What ionotropic glutamate receptors allows calcium influx?

A

NMAR

AMPAR (those without GluA2 subunit)

18
Q

How does Gq couples GPCRs increase calcium?

A

Formation of ip3 which acts on IP3R on SER

Note SERCA uses ATP to restore calcium stores in SER

19
Q

Where can calcium come from to cause CICR?

A

VGCC
Ionotropic receptors
Intracellular stores

20
Q

What receptors does calcium act on on the SER?

A

Ryanodine

21
Q

Where does CICR occurs?

A
Skeletal muscle
Cardiac myocytes (approx 80% comes from intracellular stores)
22
Q

What is another ligand for ryanodine receptors?

A

Cyclic adp ribose

23
Q

What is the role of the mitochondria in calcium levels?

A
Can uptake via a calcium uniporter
 deals with high concentrations within a microdomain (act as a buffer)
Low sensitivity (low affinity , high capacity)
24
Q

How is the mitochondria important in calcium modulation?

A

Calcium amplification

Spaciotemporal signalling

25
Q

What is calcium moved to after taken up by mitochondria?

A

The ER

26
Q

What is the role of calcium in the mitochondria?

A
Stimulates mitochondrial metabolism (rise in Ca2+ signals more ATP needed to pump out)
Cell death (PD)
BCL-2 important of calcium handling
27
Q

How is basal calcium returned to normal?

A

Termination of calcium signal
Calcium removal
Calcium store refill

28
Q

How is the SER refilled with calcium after depletion?

A

Ca2+ not bound to EF hand motif on internal surface of STIM1 in ER
This allows STIM1 aggregation (normally inhibited by Ca2+)
STIM1 interact with eachoether via coiled coil domain
Cytosolic STIM1 then interacts with Oria 1 channel (Store operated calcium channel) which allows ca2+ entry
SERCA then pumps calcium into SER
Calcium binds to STIM1 EF hand motif and causes uncoupling of oria1 and STIM1

29
Q

It what cell types do storage operated calcium channel sfunction in?

A

Non excitable cells and excitable cells

30
Q

What 3 techniques can be used to measure intracellaul Ca2+?

A

Radioisotope
Electrophysiology
Fluorescent calcium indicator

31
Q

What fluorescent indicator can be used to measure calcium?

A

Fluo-4

32
Q

Since fluo-4 cannot pass through the cell memebrane how must it be administered?

A

Microinjection directly into cell

Given as fluo-4 acetoxymethyl ester which is degraded by intracellular esterases into Fluo-4

33
Q

What happens when calcoum binds to fluo-4

A

It fluoresces which allows visualisation of calcium levels in real time

34
Q

What are the different types of calcium signals?

A

Wave
Blip
Puff

35
Q

How can calcoum regulate so many processes?

A

Differences in space, time and amplitude

36
Q

How does space dictate the processes calcium regulates?

A

Space is dependant on calcium influx which can be different places in the cell e.g. Localised to intracellular store or plasma membrane

37
Q

Five an example of global and elementary increases in calcium

A

Global - gene transcription and muscle contraction

Elementary - microdomains, neurotrasmission

38
Q

How can time regulate calcium signalling?

A

Can be a transient or prolonged increases which have different effect.
Transients avoid cell death
Prolonged calcium signalling may be inflated in cell death, cell proliferation and inflammatory response

39
Q

What can influence calcium pattern over time?

A

Different receptors show different calcium concentration patterns over time upon activation
This may produced different effects and modulate what a cell does in responce to receptor activation

40
Q

How does amplitude regulate how calcium modulates many cellular responses?

A

Strength of signal related to site of transient