lecture 18 Flashcards
what is the amplifier in the phosphoinositide pathway?
beta form of phospholipase C (PLC-B)
what is the purpose of the phosphoinositase pathway?
based off phosphorylation and dephosphorylation needed for cell signalling
what does the PLC-B do?
splits PIP2 molecule into diaceylglycerol and IP3
what does the diacylglycerol do?
stays in plane of membrane - eventually activates protein kinase C
what does the IP3 do?
releases Ca2+ from the endoplasmic reticulum
why does IP3 diffuse to the cytosol?
-due to its negative charge
-can act on ion channels to release stored calcium (that’s in ER)
what causes an increase in Ca2+ spike frequency?
hormone concentration
what does CICR cause?
regenerative Ca2+ release
how are the calcium waves brought about?
-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)
what 2 components do intracellular Ca2+ signals have?
temporal (spike)
spatial (wave)
when is the peak reached?
-when whole cell is full of calcium
-wave propagated across whole cells
why does the wave spread across the whole cell and neighbouring?
as calcium moves, it triggers its own release
what would occur if no CICR was present?
-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)
why isn’t diffusion the best way for calcium movement?
Ca2+ movement is very slow as relies solely on diffusion
what do the buffers cause?
no rise in calcium - no wave/spike as effect buffered
why do we have CICR?
why are the buffers and OFF mechanisms so strong?
Ca2+ is cytotoxic, can be toxic to body so needs strong mechanisms to protect against potential side effects
what is the Ca2+ wave?
the spatial correlate/equivalent of the spike
what is the Ca2+ spike?
temporal correlate/equivalent of the wave
where does the Ca2+ spike occur?
in mast cells
what can Ca2+ waves be propagated by?
InsP3rs and RyRs
where are InsP3Rs found?
hepatocytes (liver cells), neurones, secretory cells, eggs
where are RyRs found?
cardiac myocytes, neurones, secretory cells, eggs
what is RyR?
release calcium from internal stores during excitation contraction coupling in muscles
what is cADPR and what is its function?
-cyclic adenosine diphosphate ribose
-stimulates Ca2+ release from the RyR
-works in similar way can propagate a calcium wave
what happens to channels in presence of coagonists?
-channels can behave as CICR channels and release calcium when stimulated by the calcium
-allows regenerative Ca2+ release
what is a coagonist?
a drug/chemical that can bind to a receptor to enhance the effect
how are InsP3Rs and RyRs regulated?
-in biphasic manner by cytosolic Ca2+
-stimulation and inhibition phase
what does InsP3R require?
both InsP3 (coagonist) and Ca2+
what does RyR require?
only Ca2+
what do the channels require for maintaining them?
-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
what causes the calcium spark?
RyR
what happens with the elementary Ca2+ release events?
-stays highly localised
-calcium spark represents calcium release from cluster of ryanodine receptors
