9 - Signalling via Calcium - Williamson Flashcards
explain why Ca is unusual as a signalling molecules
- 2nd messenger
- behaves as a binary signal, on/off. strange for 2nd messengers because normally strength of signal proportional to amount of 2nd messenger. not with calcium, high amounts of Ca = ON and low amounts = OFF. no in between
- Ca is not made/degraded it is stored in ER/outside of the cell and moved in
state the resting intracellular and extracellular [Ca2+] and state what the intracellular [Ca] rises to upon receiving signal
intracellular; < 10^-7 M
extra; 10^-3 M
rises to around 10^-6 (factor of 10)
how do cells work to [Ca2+] low inside cells?
- Ca pumps pump OUT Ca from the cytoplasm and into the ER)
- Ca channels regulated by signals
(need some mechanism of recognising a rise in intracellular [Ca])
why is it good that there is a large difference in Ca conc between the inside and outside of a cell?
- because the gates do not need to be open for v long to see a change in [Ca]
describe the differences in Na and K conc inside and outside of the cell and state how much ATP is used to maintain these gradients in various cells
- Na is 10-30x lower inside cells than out
- K is 10-30x higher inside cells than out
- around 25% of ATP in eukaryotic cells required to maintain this gradient (around 65% in neurons)
how does the comparison of Na and K conc inside / outside the cells compare to Ca2+ conc difference inside & outside the cells?
Ca2+ conc is typically 10,000 times lower inside than out of the cells. shows how much harder the cell has to work to keep this gradient
describe the 2 main types of Ca pump
1) ATP - P-type Ca2+ ATPase
- pumps out one Ca for 1/2ATPs
- found in all eukaryotic cells
- eg sarcoplasmic reticulum in muscle stores Ca to stimulate muscle contraction. around 90% of membrane protein here is P-type ATPase . allows for Ca conc to be reset within 30ms
2) Na gradient utilised
- one Ca out; 3Na in
- one Ca + 1 K out; 4 Na in (works even harder!)
this is found in cells that do lots of signalling eg muscle, nerve cells
extra pumps that pump Ca into the ER
name the 2 signals that allow Ca gates to be opened
- GPCR activation eventually leading to IP3 production and binding to IP3 gated channels
- membrane depolarisation
how does the activation of a GPCR lead to Ca release from intracellular stores? what is the result of this ca release?
- activated GPCR -> activates Gqa -> activates PLCy
- cleaves PIP2 in membrane to release soluble IP3
- IP3 binds to IP3 gated ion channels on ER leading to release of Ca2+ to the cytoplasm due to the Ca gradient
- Ca2+ then binds and activates PKC -> cellular effects eg P and activation of metabolic enzymes and TFs
what is the long name for IP3
inositol 1,4,5-triP
what is an additional function of IP3
fertilisation of the egg by the sperm
describe cell membrane depolarisation and how it leads to an influx of Ca2+ . draw a diagram of this
- eg action potential passing along plasma membrane eg in muscle cell
- membrane depolarisation causes opening of Ca2+ channels, influx of Ca2+ (Ca2+ channels present in T-tubule membrane)
- influx of Ca2+ through T tubule allows activation of ryanodine R when Ca binds. causes opening and release of more Ca from intracellular stores eg from Sarcoplasmic reticulum in muscle cells
overall, state the 2 main ways in which Ca2+ can be release into the cell
- depolarisation leading to activation of voltage-gated Ca channel
- activation of Ryanodine receptor leading to release of intracellular stores of Ca
what is positive feedback in terms of Ca channels. what is positive feedback responsible for?
some Ca channels activated by Ca itself providing amplification through positive feedback eg ryanodine receptors
- responsible for the waves and oscillations seen inside cells that can travel further than simple changes in Ca conc would
Ca conc are not the ____ across the cell - there are large _____
same
gradients
