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psc2002 > lecture 18 > Flashcards

lecture 18 Flashcards

1
Q

what is the amplifier in the phosphoinositide pathway?

A

beta form of phospholipase C (PLC-B)

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2
Q

what is the purpose of the phosphoinositase pathway?

A

based off phosphorylation and dephosphorylation needed for cell signalling

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3
Q

what does the PLC-B do?

A

splits PIP2 molecule into diaceylglycerol and IP3

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4
Q

what does the diacylglycerol do?

A

stays in plane of membrane - eventually activates protein kinase C

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5
Q

what does the IP3 do?

A

releases Ca2+ from the endoplasmic reticulum

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6
Q

why does IP3 diffuse to the cytosol?

A

-due to its negative charge
-can act on ion channels to release stored calcium (that’s in ER)

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7
Q

what causes an increase in Ca2+ spike frequency?

A

hormone concentration

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8
Q

what does CICR cause?

A

regenerative Ca2+ release

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9
Q

how are the calcium waves brought about?

A

-occurs because of CICR
-Ca2+ released from IP3 feeds forward and triggers Ca2+ release through CICR of neighbouring bit of ER
-occurs multiple times to form a calcium wave
-Ca2+ generates own release as goes through the cell (results in propagating wave)

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10
Q

what 2 components do intracellular Ca2+ signals have?

A

temporal (spike)
spatial (wave)

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11
Q

when is the peak reached?

A

-when whole cell is full of calcium
-wave propagated across whole cells

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12
Q

why does the wave spread across the whole cell and neighbouring?

A

as calcium moves, it triggers its own release

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13
Q

what would occur if no CICR was present?

A

-cell would rely on diffusion of Ca2+ ions
-some Ca2+ binds sensing proteins which will induce a response in the cell
-ca2+ bind to buffers (soak up the calcium)

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14
Q

why isn’t diffusion the best way for calcium movement?

A

Ca2+ movement is very slow as relies solely on diffusion

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15
Q

what do the buffers cause?

A

no rise in calcium - no wave/spike as effect buffered

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16
Q

why do we have CICR?

A
17
Q

why are the buffers and OFF mechanisms so strong?

A

Ca2+ is cytotoxic, can be toxic to body so needs strong mechanisms to protect against potential side effects

18
Q

what is the Ca2+ wave?

A

the spatial correlate/equivalent of the spike

19
Q

what is the Ca2+ spike?

A

temporal correlate/equivalent of the wave

20
Q

where does the Ca2+ spike occur?

A

in mast cells

21
Q

what can Ca2+ waves be propagated by?

A

InsP3rs and RyRs

22
Q

where are InsP3Rs found?

A

hepatocytes (liver cells), neurones, secretory cells, eggs

23
Q

where are RyRs found?

A

cardiac myocytes, neurones, secretory cells, eggs

24
Q

what is RyR?

A

release calcium from internal stores during excitation contraction coupling in muscles

25
Q

what is cADPR and what is its function?

A

-cyclic adenosine diphosphate ribose
-stimulates Ca2+ release from the RyR
-works in similar way can propagate a calcium wave

26
Q

what happens to channels in presence of coagonists?

A

-channels can behave as CICR channels and release calcium when stimulated by the calcium
-allows regenerative Ca2+ release

27
Q

what is a coagonist?

A

a drug/chemical that can bind to a receptor to enhance the effect

28
Q

how are InsP3Rs and RyRs regulated?

A

-in biphasic manner by cytosolic Ca2+
-stimulation and inhibition phase

29
Q

what does InsP3R require?

A

both InsP3 (coagonist) and Ca2+

30
Q

what does RyR require?

A

only Ca2+

31
Q

what do the channels require for maintaining them?

A

-ATP binding in one of the intracellular domains (allows to behave as CICR if high enough energy)
-used as safety mechanism to prevent cytotoxic effects

32
Q

what causes the calcium spark?

A

RyR

33
Q

what happens with the elementary Ca2+ release events?

A

-stays highly localised
-calcium spark represents calcium release from cluster of ryanodine receptors

34
Q
A
35
Q
A

psc2002 (15 decks)

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