PSC2002/L18 Calcium Signalling II

Question 1

Describe the phosphoinositide pathway. (5)

Answer 1

Receptor activation of GPCR or RTK
PLC activation to break down PIP2 into IP3 and DAG
Calcium release from ER triggered by IP3
PKC activation by DAG - PKC phosphorylates target proteins
PI3K pathway (alternative): PI3K generates PIP3 activating downstream proteins like Akt

Question 2

What is the role of DAG?

Answer 2

Second messenger
Acts within lipid bilayer to stimulate effector IP3

Question 3

What is the role of IP3?

Answer 3

Second messenger
Diffuses into cytosol and acts on ion channels to release Ca2+ stored in ER

Question 4

Describe a series of Ca2+ spikes.

Answer 4

Ca2+ spike frequency increases with hormone concentration
Similar amplitude waves

Question 5

What kind of calcium release results from CICR?

Answer 5

Regenerative calcium release

Question 6

Describe regenerative calcium release.

Answer 6

Ca2+ feed forward to promote further Ca2+ release from neighbouring parts of cell (e.g., ER)

Question 7

What is the:
a) temporal
b) spatial
component of intracellular Ca2+ signals?

Answer 7

a) wave is spatial correlate
b) spike is temporal correlate

Question 8

What is a regenerative Ca2+ signal required for?

Answer 8

To saturate buffers and to generate Ca2+ waves and spikes

Question 9

What rate do Ca2+ waves propagate at in cardiac myocytes?

Answer 9

5-100um/s

Question 10

What can Ca2+ be propagated by? (2)

Answer 10

InsP2Rs
RyRs

Question 11

Which receptors do hepatocytes contain?

Answer 11

Only InsP3Rs

Question 12

What receptors do cardiac myocytes contain?

Answer 12

Mostly RyRs

Question 13

Which cells contain both InsP3Rs and RyRs? (3)

Answer 13

Neurones
Secretory cells
Eggs

Question 14

What are RyRs sensitive to? (3)

Answer 14

NOT IP3
Cyclic adenosine diphosphate ribose (cADPR)
Different Ca2+ release to InsP3 receptor

Question 15

What confers CICR ability on a receptor?

Answer 15

Co-agonist presence

Question 16

Describe the biphasic manner of INSP3R and RyR regulation.

Answer 16

First phase - stimulatory
Second phase - active inhibition

Question 17

Which receptor is less sensitive to calcium?

Answer 17

RyR

Question 18

What is the effect of cADPR on the [Ca2+]-Ca2+-release curve?

Answer 18

Makes receptors more sensitive to Ca2+ - shift to left

Question 19

When won’t a cell produce a calcium signal?

Answer 19

If it has low energy levels (can’t activate OFF mechanism) due to cytotoxic high [Ca2+]

Question 20

What is required by:
a) InsP3R
b) RyR?

Answer 20

a) InsP3 & Ca2+, ATP
b) Ca2+ & ATP
ATP BINDING not hydrolysis