Regulation of Intracellular Calcium Levels Flashcards
What is the extracellular level of ca2+?
1 x 10-3 M (1 mM)
What is the cytoplasmic level of ca2+?
100 nM or 1 x 10-7 M or 0.1 microM
What is the difference between extracellular and cytoplasmic levels of ca2+?
Difference of 10,000
What are the levels of ca2+ in the ER/SR?
2 x 10-4 M
How are increases in cytoplasmic Ca2+ concentration mediated?
By movement of Ca2+ across the plasma membrane and release of Ca2+ from the ER/SR
How are increases in cytoplasmic Ca2+ concentration opposed?
Relative impermeability of the plasma membrane to Ca2+, pumps and transporters that move Ca2+ out of the cytoplasm and Ca2+ buffer proteins (Ca2+ binding proteins)
What receptors/pumps/transporters on the plasma membrane let calcium into the cell?
VGCC – lets calcium in when cell reaches a certain voltage
LGCC – lets calcium in when ligand (eg a hormone) binds to the receptor and opens it
NCX – (can work both ways) – 3 sodium in for 1 calcium out
SOC - comparatively very slow - importnt in accessing extracellular Ca2+ when the SER stores for Ca2 are depleted
What receptors/pumps/transporters on the plasma membrane let calcium out of the cell?
Plasma Membrane Ca2+ ATPase (PMCA) – uses ATP to pump calcium against its concentration gradient out of the cell
NCX – (can work both ways) – 3 sodium out for 1 calcium in
What receptors/pumps/transporters on the ER/SR decrease cytosolic Ca2+ levels?
S/ER Ca2+ ATPase (SERCA) - uses ATP to pump calcium into SR/ER
What receptors/pumps/transporters on the ER/SR increase cytosolic Ca2+ levels?
Calcium induced calcium release (CICR) - Ryanodine receptors
IP3 receptors
By how much can activation of IP3 R increase cytoplasmic concentration of calcium ions within a few seconds?
By 5-10 fold
In which type of muscles are store operated channels important?
Smooth muscle where prolonged states of stable contraction are required
Which channels are important in accessing extracellular Ca2+ when the SER stores for Ca2+ are depleted?
Store operated channels
What are SOCs activated by?
Special Ca2+ sensing protein in the SER which detects when the Ca2+ concentration in the SER is low and interacts via close apposition to the SOC channel.
How many ATP molecules does PMCA use to transfer one calcium ion out of the cytosol?
One
How is the affinity of PMCA to calcium ions further optimised?
When it binds with Calmodulin, a cytoplasmic Ca2+ sensing protein
What is the source of the energy used by NCX?
Does not use ATP directly, uses the electrochemical energy gradient provided by the large concentration of extracellular Na+ to exchange 3 Na+ in for every one Ca2+ pumped out
Which is the primary pump of Ca2+ when levels are > 10 micromolar?
NCX
Where is NCX especially active?
In excitable tissues such as nerve and muscle where continuous large movements of Ca2+ underpin physiological activity
When does the NCX act in reverse?
In heavily depolarised cells if the intracellular sodium concentration increases significantly. Moves 3 Na+ out for every one Ca2+ in.
Which type of GPCR contributes to regulation of Ca2+ efflux from the intracellular stores?
Gq
What acts as the ligand on ryanodine receptors?
Ca2+
Why are ryanodine receptors associated with calcium induced calcium release in smooth and cardiac muscle?
With depolarisation of the t-tubule, the VGCCs open and allow an influx of Ca2+. This Ca2+ then binds with the RyR which results in a very large synchronous outward low of SR Ca2+ into the sarcoplasm.
Why are ryanodine receptors associated with calcium induced calcium release in skeletal muscle?
RyR still activated by increased concentration of intracellular calcium concentration however there is a structural modification whereby the T-tubule VGCCs are directly physically coupled to the RyR receptor. This channel coupling means that when the VGCCs open, the RyRs also open and release massive amounts of Ca2+ into the sarcoplasm.
