calcium singalling Flashcards
how do specific calcium codes differ?
the frequency, amplitude and duration of caclium osscilations determine the end result of selective intracellular activation processes
what is the normal physiological range cytosolic and extracellular calcium
extracellular - 1.4mMol
intracellular 100nMol at rest
so calciuim has one of the largest ioninic gradients
name some regulatory machinery for calciuim
Okay but how regulate
calcium pumps
ATP ases and exchangers like PMCA, SERCA
na/ca exchanger
STIM 1 and Orai1 CRAC channels as well for SOCE to replenish ouur stores of calcium
how can intracellular calcium levels be induced
stimuli bind to receptors on cell surface, leads to second messenger levels rising of
inositol triphosphate -ip3
cyclic adp robdoe
naadp (Nicotinic acid adenine dinucleotide phosphate)
how does calcium maintain its low intracellular/cytocsolic conc?> (100nmol)
- using pumps and exchangers
- sequeste/store calcium in SR, ER, mitch
- chelating calcium, having it bound to proteins
how can calcium be put into its stors?
SERCA pumps are located on the membrane of endo/sarcoplasmic reticulum to store calcium
there are also mitochondrial uniporters
which receptors are present on the ER?
Ip3 receptors and ryanodine receptors which mediate calcium release from the Stores
how do non excitable cells become activted
they do not have voltage gated ion channels so cannot generate an AP, rely on a second messenger
= calcium release from intracellular stores, which can then activate processes like granular secretion as seen in PAC
how can we replenish the ER store ?
via store operated calcium entry
use the STIM1 ER membrane proteins which respond to low calcium in ER and interact with plasma membrane to TO ACTIVATE ORAI proteins and activate the CRAC channels
calcium entry then moves through the ER pump to remain in ER
in very toxic high intracellular calcium, we can inhibit this oligomerisation of STIM1
