Control of Intacellular Calcium Flashcards
Give 8 examples of cellular processes that are calcium sensitive
Fertilisation, Secretion, Neurotransmission, Metabolism, Contraction, Learning and memory, Apoptosis, Necrosis
How can Ca be metabolised?
It can’t
How does the cell regulate intracellular Ca concentration?
Based largely on moving Ca into and out of the cytoplasm
What is the extracellular concentration of Ca at rest
1-2mM
What is the intracellular concentration of Ca at rest?
100nM
What is the problem with the tight regulation of Ca levels?
The large gradient is energy expensive
What are the advantages of the large Ca gradient?
Changes in intracellular Ca occur rapidly and with little movement
What are the disadvantages of the large Ca gradient?
Ca overload leads to loss of regulation and cell death
What does the Ca gradient rely on?
The relative impermeability of the plasma membrane
The ability to expel Ca across the plasma membrane
Ca buffers
Intracellular Ca stores
What gives the ability to expel Ca across the plasma membrane?
Ca ATPase
Na-Ca Exchanger
What are the types of intracellular Ca stores?
Rapidly releasable
Non-rapidly releasable
What is membrane permeability regulated by?
The open/closed state of ion channels
What is the affinity of Ca ATPase?
High
What is the capacity of Ca ATPase?
Low
How does Ca ATPase work?
Intracellular Ca increases
Ca binds to calmodulin- a binding trigger protein
Calmodulin-Ca binds to Ca ATPase
Ca is removed from cell
What is the affinity of the Na/Ca Exchanger?
Low
What is the capacity of the Na/Ca Exchanger?
High
What is required to drive the Na/Ca Exchanger?
The Na gradient produced by Na/K-ATPase
How many Na are transported for how many Ca in the Na/Ca Exchanger?
3 Na in for 1 Ca out
What does the Na/Ca Exchanger do for the charge of the membrane?
Nothing- the antiporter is electrogenic
When does the Na/Ca Exchanger work best?
At resting membrane potential
What do Ca buffers do?
Limit diffusion
How do Ca buffers limit diffusion?
Through ATP and Ca binding proteins
Give 4 examples of Ca binding proteins
Parvalbumin
Calreticulin
Calbindin
Calsequestin
What does diffusion of Ca depend on?
The concentration of binding molecules, and their level of saturation
What happens when some other proteins bind Ca?
It alters their function
Give an example of a protein that changes function on Ca binding
Calmodulin
How high can Ca levels rise when it is being used to regulate cellular activity?
~1µm
How is intracellular Ca concentration increased?
Ca influx across the plasma membrane due to altered permeability
Ca release from ‘rapidly releasable’ and ‘non-rapidly releasable’ stores
How does the permeability of the membrane allowing Ca influx change?
Voltage gated Ca channels
Receptor operation ion channels (ionotropic receptors)
What controls Ca release from rapidly releasable stores?
G-protein coupled receptors
Ca induced Ca release
What are voltage-gated calcium channels?
Channels that open to allow the influx of calcium down its concentration gradient, triggered by membrane depolarisation
How does a receptor operated Ca channel work?
A ligand/agonist binds to the channel, opening it and allowing Ca to enter down its concentration gradient
Where are stores of Ca set up inside the cell?
In the sarco/endoplasmic reticulum
How are Ca stores set up in the sarco/endoplasmic reticulum set up?
By the SERCA protein.
Ca moved in using energy from ATP hydrolysis
What happens once Ca has been moved into the sarco/endoplasmic reticulum?
It binds to proteins such as calsequestrin
How do G-protein coupled receptors alter intracellular Ca concentration?
A ligand binds to the GPCR on the cell membrane, activating its Gαq subunit. This subunit then binds to the membrane phospholipid PIP2, releasing IP3, which in turn binds to its receptor on the sarco/endoplasmic reticulum, triggering the release of Ca down its concentration gradient into the cell
How does Ca induced Ca release (CICR) work?
Ca binds to the Ryanodine receptor on the side of the sarco/endoplasmic reticulum, triggering the release of calcium down its concentration into the cell
Give an example of an important physiological role for CICR?
In the cardiac myocyte
Why is CICR important in the cardiac myocyte?
Ca entry through VOCCs following depolarisation of the membrane binds to the ryanodine receptors, causing an explosive release of large amounts of Ca from intracellular stores
What are mitochondria important, regarding calcium?
They take up Ca when intracellular concentrations are high as a protective mechanism
Participate in normal Ca signalling
Why can mitochondria take place in normal Ca signalling?
Due to microdomains
What are microdomains?
Areas of cytoplasm with higher concentration of Ca due to their proximity to a channel
What is the purpose of mitochondria taking up Ca?
Aids in buffering, regulating, signalling, and stimulation of ATP production
How do mitochondria take up Ca?
Via a Ca uniporter
What drives the Ca uniporter in mitochondria?
Respiration
What does repetitive signalling require?
A return to the basal state
What happens if there is too much Ca for too long?
It’s toxic to cell
What does a return to basal Ca require?
Termination of signal
Ca removal
Ca store refilling
How are Ca stores refilled?
By recycling of cytosolic Ca
Using Ca stored in mitochondria to replenish SR stores
How does the Ca stored in mitochondria replenish the SR stores?
Via the store-operated Ca channel (SOC)
