Control Of Intracellular Calcium Concentration (5.2) Flashcards
What is calcium responsible for or regulate?
Fertilisation Proliferation Secretion Neurotransmission Metabolism Learning and memory Apoptosis and necrosis
Why do calcium levels have to be closely controlled?
Ca cannot be metabolised therefore have to move it in and out of the cytoplasm
What are the advantages and disadvantages to a steep Ca concentration gradient?
Advantages – Increases in Ca concentration occurs rapidly with little Ca movement
Disadvantages – Ca overload leads to loss of regulation and cell death
What does the set up and maintenance of a Ca gradient rely on?
- Impermeable membrane
- Ability to expel Ca across membrane using:
- – Ca ATPase and Na-Ca exchanger
- Ca buffers
- Intracellular Ca stores
- – rapidly and non rapidly releasable
How is the permeability of the membrane regulated?
Is regulated by the open or close state of ion channels
Describe the action of the Ca ATPase
Moves Ca out at the expense of ATP so against a chemical. And concentration gradient
Describe the feedback mechanism for Ca ATPase
What characteristic for affinity and capacity does it have?
An increase in [Ca] occurs and Ca binds to calmodulin (trigger protein)
The Ca-calmodulin complex binds to Ca-ATPase
The Ca-ATPase removes Ca from the cell
– high affinity and low capacity
Describe the action of the Na/Ca exchanger.
What capacity and affinity does the channel have?
[Na] is into the cell, so it is used as the driving force using a Na-K-ATPase
Antiporter is electrogenic so it removes calcium best at a resting potential
Allows for Ca to be removed against its concentration gradient
Low affinity with a high capacity
(Good at high concentrations)
What do calcium buffers do?
Limits calcium diffusion in the cell
– independently regulates the movement of ions
What are the effects of calcium buffers?
Name some Ca buffers
What happens when there is an incresed saturation for the buffers?
How far can a Ca ion normally diffuse before it encounters a buffer molecule?
Ca diffuses more slowly.
Calreticulin, calbindin and calsequestrin
Ca can diffuse further in the cell because it is not limited by the buffer
Normal amount of diffusion to reach a binding molecule is 0.1 -0.5 micrometres
How is the [Ca] elevated then returned to normal levels?
- Ca influx across the membrane through specific channels
- – voltage gated channels and receptor-operated ion channels - Ca is released from rapidly releasable stores
- – G-protein coupled receptors and calcium induce Ca release - Non-rapidly releasable stores
Describe the two ways that Ca influx occurs across a plasma membrane
Voltage operated Ca channels
– senses depolarisation which opens an aqueous pore to allow Ca into the cell
Ionotropic receptors (receptor-operated ion channels) -- e.g. NMDA receptors for glutamate and nicotinic ACh receptors
What facilitates the relates of Ca from rapidly releasable stores?
How does in it get Ca into the store?
What is the concentration of Ca inside the stores?
SERCA pump – sarcoplasmic/endoplasmic reticulum Ca2+ ATPase
Uses ATP to bring Ca in against its steep gradient. The Ca binds to calsequestrin. The release of Ca is controlled by release channels.
Concentration = 1mM
What are the two ways that the release of Ca from intracellular stores is controlled?
- G-protein coupled receptors
2. Calcium induced calcium release
Describe the process of calcium release via G-protein receptors
Where are G-protein receptors found?
What proportion of drugs target these receptors?
Molecule binds to receptor which interacts with a G-protein which mediate the release of effector molecules inside the cell.
Majority of cells contain G-protein receptors
30-50% of drugs target these receptors
