what happens in intracellular Ca2+ signalling?
-hormones, growth factors & neurotransmitters bind to the receptor
-Ca2+ released
-causes a response eg. change in permeability, secretion, contraction, metabolism, fertilisation etc.
what compound releases Ca2+ in the phosphoionsitide pathway?
IP3
how is calcium concentration kept low in cells?
by the OFF mechanisms (turn calcium signal off to keep inside conc low)
what are the different OFF mechanisms?
- Ca-ATPase pumps
- Na/Ca exchanger
- mitochondria
- proteins (+lipids)
what occurs at the Ca-ATPase pumps?
-ATP hydrolysed to ADP
-pumps calcium ions out the cell using the energy produced
what happens at the Na/Ca exchanger?
-exchanges sodium ions coming in for calcium ions leaving
-driven by the inward sodium gradient
-expels sodium ions from the cell and replaces with calcium ions
how does the mitochondria maintain help maintain low intracellular calcium conc?
it takes up calcium to act as a buffer
why can OFF mechanisms work over a range of Ca2+ concentrations?
to protect the cytotoxic effect of calcium over a wide range of concentrations
which gradient in exploited in order to generate calcium movement?
inward calcium gradient (so moves into cell)
what are the 3 types of Ca2+ signal?
- elementary events
- global Ca2+ wave (intracellular)
- global Ca2+ wave (intercellular)
what are the elementary events?
-calcium signals trigger exocytosis of vesicle/in vicinity of nucleus - so calcium enters nucleus and triggers gene transcription
-remains highly localised in cell
what is the intracellular global Ca2+ wave?
-wave of calcium behind in one part of cell and propagates across whole cell
what is the intercellular global Ca2+ wave?
-between cells
-wave spreads into neighbouring cells
-occurs in wound healing
what happens in the phosphoinositide (PI) pathway?
- chemical signal induces a conformational change in the 7 membrane spanning receptor
- G protein becomes activated and stimulates an amplifier (phospholipase C)
- PLC acts on minor membrane PIP2 to form DAG and IP3 (second messengers)
- CICR causes the onset of the Ca2+ signal
- Ca2+ uses specific binding proteins to induce contractions in muscle cells/directly acts on ion channels to influence excitability
what does CICR stand for?
calcium intake calcium release
where does DAG act?
-within plane of lipid bilayer
-stimulates an effector (protein kinase C)
what is the function of IP3?
-diffuses into cytosol
-acts on ion channels to release Ca2+ stored up in endoplasmic reticulum
