Calcium Flashcards
Which properties of calcium allow it to interact with a wide range of varied molecules?
- Divalent - strongly attracted to negatively charged/polarised points on biological molecules.
- ‘Polarisable’ electron clouds - can bind in variety of irregular surfaces/enclosed spaces.
- Squishiness - wide range of bonding angles and great variability in bond length.
How does calcium binding to a protein change the activity of that protein?
1 - Ca2+ binds to exposed O2 atoms of protein’s aa.
2- Causes conformational change in protein structure - physical work or further signalling.
3- ATP-driven activity to remove Ca2+ - protein back to resting state.
What is the proportionate conc. difference between extracellular and intracellular calcium?
10,000 x
Name the intracellular calcium stores.
- Mainly smooth ER (or sarcoplasmic reticulum in muscle): rapid release store.
- But also mitochondria (buffer excessive [Ca2+]i levels): slow release
What are the extracellular, intracellular and intracellular store concentrations of calcium?
- Extracellular: 1 x 10^-3 M (1 mM)
- Intracellular: 1 x 10^-7 M (100 nM)
- sER: 2-3 x 10^-4M (300 uM - 1mM)
Which channels enable Ca2+ entry from the extracellular space into the cytosol? What do they open in response to?
- Voltage-operated calcium channel (VOCC)
- membrane depolarisation
- Ligand-gated ion channel (LGIC)
- binding of excitatory NTs
- Store-operated channel (SOC)
- low [Ca2+]SER and very active PMCA - opened by Ca2+ sensor in SER membrane
Where are SOCs important? Why?
- In smooth muscle where prolonged states of stable contraction are required.
- Channel has very low conductance and operates over seconds - comparatively slow.
Which molecules allow calcium efflux from the cytosol to the extracellular space?
- Na+/Ca2+ exchanger (NCX)
2. Plasma membrane Ca2+ ATPase (PMCA)
How do the NCX and PMCA transport Ca2+ out of the cell?
NCX:
- Utilises electrochemical energy gradient provided by large conc. of extracellular Na+.
- 3 Na+ in for 1 Ca2+ out.
PMCA:
- Uses 1 ATP molecule.
When and where is each Ca2+ transporter used?
NCX
- Primary pump when high [Ca2+]i.
- Has lower Ca2+ affinity but high capacity as extensively expressed in many cell types.
- Esp active in excitable tissue, e.g. Nerve and muscle, where continuous large movement of Ca2+ underpins activity.
PMCA
- High Ca2+ affinity (esp when binds with calmodulin) but low expression - role in fine tuning [Ca2+]i.
- Expressed in all cell types.
Which molecule allows calcium uptake from the cytosol to the intracellular store?
- Smooth/sarco endoplasmic reticulum calcium ATPase (SERCA)
- Enables rapid re-establishment of basal [Ca2+]i following external stimulus of cell.
- Requires ATP as transports Ca2+ against very steep concentration gradient.
Which molecules enable calcium movement from the intracellular store to the cytosol?
- IP3R
- Ryanodine receptor (RyR)
Describe how the opening of IP3R is regulated.
- Ligand binds to GPCR - activates Gq.
- Activates PLC - conversion of PIP2 to IP3.
- IP3 binds to IP3R (LGIC) - calcium efflux from SER/ER.
Describe how the opening of RyR is regulated?
Calcium induced calcium release:
- T-tubule depolarisation - VOCC opens (and LGIC) - calcium influx.
- Calcium acts as ligand for RyR (LGIC) - very large synchronous efflux of SER calcium into sarcoplasm.
In which cell type is RyR mainly expressed?
Muscle cells
