Flashcards in 9. Control Of Cytosolic Ca2+ Deck (12)
What are some disadvantages of the large inward gradient of calcium?
It is energy expensive to maintain, Ca2+ overload is easy with slight loss of regulation and can lead to cell death.
How is the large inward gradient of calcium set up and maintained?
Relative impermeability of plasma membrane - regulated by open/close state of ion channels.
Expulsion of Ca2+ across the plasma membrane using:
-Ca2+ATPase: high affinity, low capacity. [Ca2+]i increases, Ca2+ binds to cal modules, Ca2+-cal modules binds Ca2+ATPase, Ca2+ATPase removes Ca2+.
- Na+/Ca2+ exchanger: low affinity, high capacity. [Na+] gradient used as driving force. Anti porter is electrogenic and works best at resting membrane potential.
- Ca2+ buffers. They limit Ca2+ diffusion, diffusion depends on concentration of binding molecules and their level of saturation.
What are trigger proteins?
Some proteins bind Ca2+ and alter function. They regulate free [Ca2+].
How is [Ca2+]i elevated and returned to basal levels?
- Ca2+ influx across the plasma membrane.
A) voltage operated Ca2+ channels: regulated by voltage and undergo conformational changes so calcium can diffus in down the concentration gradient.
B) ionotropic receptors: binding of the ligand (calcium) causes conformational change so channel opens and exposed the pore and Ca+ can move through.
- Ca2+ is released from rapidly releasable intracellular stores, like the endoplasmic reticulum. SERCA pump allow entry of calcium into th endoplasmic reticulum, it then acts as a store that can be released via release channels.
- Non-rapidly releasable stores, like mitochondria.
How is Ca2+ release from endoplasmic reticulum mediated?
Via G protein coupled receptors, G protein released from the ligand binding to GPCR reacts with PIP2 and is cleaved into IP3 which opens the IP2 receptor to allow exit of Ca2+ from the stores.
Also by use of Ca2+ induced Ca2+ release (CICR). Ca2+ influx from the VOCC acts on the CICR to allow more release from the stores of Ca2+.
Where does the Ca2+ that acts on Ca2+ induced Ca2+ release channels come from?
VOCCs, ionotropic receptors and intracellular stores.
What are the landmark features of cardiac action potentials?
0 - upstroke because of Na+ channels opening and Na+ moving in
1 - brief repolarisation as K+ and Cl- move out
2 - plateau as Ca2+ moves in via VOCC and K+ out
3 - rapid repolarisation as K+ moves out
How do mitochondria uptake Ca2+?
Via uni porters - low affinity, high capacity.
What is the role of mitochondrial Ca2+ uptake?
Ca2+ buffering - regulate pattern and extent of Ca2+ signalling.
Stimulation of mitochondrial metabolism - match energy demand and supply.
Role in cell death - apoptosis.
How do [Ca2+]i return to normal?
Ca2+ store refilling.
How do Ca2+ stores refill?
There is a depleted signal, so the capacitative or store-operated channel (SOC).