Control Of Cytosolic Calcium Flashcards
Name some functions of calcium
Apoptosis Muscle contraction Neurotransmission Gene regulation Memory (LTP)
Equilibrium potential of calcium?
+123mv
What are the intracellular and extracellular conc of calcium?
Intra = 10^-7M Extra = 1-2mM
What are the advantages of a large calcium gradient?
Small influx = large conc difference
Little has to be removed to re establish resting calcium
Disadvantages of large calcium gradient?
maintaining gradient is energy expensive
Easy to overload and lead to cell death
How is the calcium gradient set up and maintained?
Plasma membrane Ca2+ ATPase
NCX
Calcium buffers
What are come characteristic of the PMCA?
High affinity, low capacitance
Therefore works when levels of calcium are low and does not shift large amounts
Uses ATP
Also regulated by calcium calmodulin complex. Increase in calcium increase complex binding to PMCA which stimulates it to remove calcium
What direction does the PMCA move calcium?
Extracellularly
What direction does the NCX move ions?
RMP = 3Na+ in 1Ca2+ out
Depolarisation reverses this
Where are some characteristics of NCX channels?
Powered by secondary activity transport by sodium gradient set up by Na+K+ATPase
High capacity low affinity
Channel is electrogenic (net + influx) means sodium harder to move in at more positive mV
Name some calcium buffers?
Calsequestrin
Parvalbumin
Calbindin
What do calcium buffers do?
Bind to calcium with no intrinsic function to slow down rise in intracellular calcium and prevent global cellular rise by maintaining calcium rise in micro-domain (within 0.1-05(micro)m)
What are calcium trigger proteins?
Bind calcium which causes an altered effect on protein
E.g. Synaptotagmin in neurotransmission
Explain synaptotagmins (ST) role in neurotransmission
ST is a V-SNARE which has a C2A and C2B domain on the cytosolic side
These bind calcium (C2a = 3 calcium, C2B = 2 calcium)
Calcium bind here follows VGCC opening which causes conformational change which allows it to interact with syntaxin (t-SNARE)
Allows for fusion
How is elevation of intracellular calcium achieved?
VOCC
Ionotropic glutamate receptors
GPCRs coupled to Gq
Calcium induced calcium release
What are some characteristics of VGCC?
Many types (N,L,P/Q,R)
Modulated by PKC
Alpha 1 subunit = 6TMDs made of 4 connected domains
May have accessory subunits
What ionotropic glutamate receptors allows calcium influx?
NMAR
AMPAR (those without GluA2 subunit)
How does Gq couples GPCRs increase calcium?
Formation of ip3 which acts on IP3R on SER
Note SERCA uses ATP to restore calcium stores in SER
Where can calcium come from to cause CICR?
VGCC
Ionotropic receptors
Intracellular stores
What receptors does calcium act on on the SER?
Ryanodine
Where does CICR occurs?
Skeletal muscle Cardiac myocytes (approx 80% comes from intracellular stores)
What is another ligand for ryanodine receptors?
Cyclic adp ribose
What is the role of the mitochondria in calcium levels?
Can uptake via a calcium uniporter deals with high concentrations within a microdomain (act as a buffer) Low sensitivity (low affinity , high capacity)
How is the mitochondria important in calcium modulation?
Calcium amplification
Spaciotemporal signalling
