Calcium Homeostasis Flashcards
Give an example of a cellular role of calcium
Concentration changes are used to transmit information through mediation of specific bond formation.
How is calcium moved through a sodium/calcium exchanger
Generally flows out of the cell down the concentration gradient (passive, no ATP required). Calcium exchanged for sodium
Where is calcium ATPase located
Endoplasmic reticulum (ER)
Where does calcium in the cytoplasm go
Pumped out of the cell by sodium/calcium exchanger
Or
Pumped into the ER (through action of calcium ATPase) or mitochondria (down electrochemical gradient)
How many calcium molecules can bind to a single calmodulin molecule?
4
What happens when calcium binds to calmodulin
Calcium/calmodulin complex formed.
Increased affinity for target enzymes due to exposure of hydrophobic regions
Inhibition of calcium/calmodulin dependent kinase 2 is stopped. Therefore it can function.
Suggest methods for measuring calcium ion levels
Radioactive labels Ion-sensitive microelectrodes Indirect electrophysiological measurements NMR spectroscopy Ion-sensitive dyes Fluorescent indicators
What types of calcium homeostasis occur in the human body
Cellular - in constant oscillation
Serum - fixed
Bone - continuously changing
What are the calcium concentrations at rest
Outside ~10^-3 M
In the ER ~ 10^-3 M
Inside <10^-7 M
Why is calcium homeostasis important
The sole function of calcium is to transmit information. Requires precise concentrations to be maintained
Summarise the movement of calcium in a cell
Passive diffusion out of the stores (mitochondria/ER) into the cytoplasm
Active transport into the ER by SERCA pumps
Diffusion into the cell through voltage- and ligand-gated ion channels
Transported out of the cell by pumps and exchangers (e.g. Na/Ca exchanger)
How is calcium pumped out of the cytosol
Na/Ca exchanger on membrane (pumps Ca out, and Na in)
Ca pump in cell membrane (pumps out calcium, but requires ATP)
How is calcium pumped into the ER and mitochondria
Ca pump in ER membrane (SERCA pump; requires ATP)
Ca-binding molecules in cytoplasm
Ca import in the mitochondria
What are the main transporters involved in calcium transportation
TRP channel (Outside calcium into cytoplasm) PMCA (calcium pumped outside) NCX (Na/Ca exchanger)(calcium pumped in/out of cell) GPCR/IP3R channel (Gq receptors activated IP3 which trigger calcium release from the ER) SERCA pump (pumps Ca into the ER)
Which calcium transporters are involved in keeping calcium concentrations low
Na/Ca exchanger BK channel (by blocking influx through VGCC/ROCC) Ca-binding molecules SERCA pump Import into the mitochondria
Which calcium transporters are involved in raising calcium levels
SMOCCs (GPCR) VGCC ROCC IP3 pathway (GPCR + ER)(activated by RTK/insulin mGluR-S etc) SOCCs
What role does Phospholipase C[beta] have with PIP3
Degrades to two messengers; DAG and IP3 (by catalysing hydrolysis of PIP3)
How does hydrolysis of PIP3 free intracellular calcium
Degraded to DAG and IP3
DAG activates PKC
IP3 activates IP3R channel which causes calcium efflux from the ER
What is the structure of IP3
6 carbon ring.
3 phosphate groups; 3 OH groups. Phosphate groups at 1,4,5 carbons.
What is the structure of the IP3 receptor (IP3R)
Tetramer. Each subunit has 6 TM domain. Each subunit has one IP3 binding site.
At least 3 known subtypes (S1-3) which modulate/express differently and found in different places
Where is the IP3R1 receptor located
Brain (esp cerebellum)
What are the two key components of calcium restocking in the ER
Sensor (to tell when the calcium store is depleted); STIM proteins
Channel (that facilitates calcium re-entry);
ORAI proteins
What is the role of STIM proteins
To detect when the ER calcium store is depleted, and activate ORAI channels
What is the structure of ORAI proteins
Tetramer protein.
3 subtypes - ORAI 1-3
