Ca and Na regulation Flashcards
What occurs if there is an increase in intracellular Na
- Decrease in inward chemical gradient
- ENa becomes less positive (=30mV) decreasing the electrical gradient
- It therefore takes longer for a potential difference to develop
- Problems arise in the formation and propagation of action potentials
- Action potentials that do fire have a slower conduction
How does the thick ascending limb regulate Na
Totally impermeable to water - favours Cl and Na reabsorption - Na/KATPase on basolateral membrane keeps intracellular Na low
NKCC2 moves one Na in along with one K and 2 Cl
K is recycled over the apical membrane via ROMK
This creates a transepithelial gradient for countercurrent multiplication
If Na is raised - NaCl reabsorption is inhibited and the transepithelial osmotic gradient is diminished
How does the Na/KATPase work
1 ATP molecule is hydrolysed in order to move 3Na out and 2K in
Na binds to the channel - ATP hydrolysis causes a protein phosphorylation in the channel - conformational change causes Na ions to be exposed to the inside of the channel - so are moved out the cell
K binds to the outside surface of the channel - Dephosphorylation of the channel protein causes another conformational change that exposes the K to the inside of the cell so is moved in
what three factors affect Na/KATPase rate of action
Dependent on the concentration of Na inside the cell and K outside the cell
Also dependent on ATP so also depends on the metabolic state of the cell
What two chemicals inhibit Na/KATPase
Ouabain and digoxin - Result in increased intracellular Na which inhibits NaCa exchanger so intracellular Ca increases - this increases contractility of cardiac muscle - hypertension - cardiac arrest
What are the normal concentrations of Ca intra and extracellularly
1mM and 100nM 10,000 - fold concentration gradient
Why is Calcium entry into a cell favoured
Due to such a high concentration gradient across the membrane and ECa being +120mV
What is the action of the Na/Ca exchanger
3Na enter the cell and 1 Ca leaves, the 3 Na result in a cubing of the electrochemical gradient - multiplied by the resting potential Na gradient being 10 fold results in a 10,000 fold gradient
What are the three types of CaATPase
PMCA - Act to pump Ca out of the cell
SERCA - Act to pump Ca out of the cytoplasm and into organelles to store Ca
SPCA - Found on golgi apparatus membrane
What are the 4 types of Ca signalling pathways
VOCC - found in excitable cells - activated by depolarisation
ROCC - Found in secretory cells and nerve terminals - activated by ligand binding
Mechanically activated - Found in many cells and respond to deformation
SOCC - activated following depletion of calcium stores
What are the two types of calcium channel in store membranes
- IP3 receptors activated by IP3 binding - expressed in most cells
- Ryanodine receptors - Low concentrations of ryanodine activate the channel - high concentrations inhibit it
Found in excitable cells - Malignant hyperthermia - MUTATION IN RYANODINE RECEPTOR - general anaesthetic increases its sensitivity leading to more Ca release into sarcoplasmic reticulum - Mitochondria have an oxidative burst - use up huge amounts of ATP - rapid rise in temperature and muscle contraction - also has effects on smooth muscle - Tachycardia, hypertension
How does calcium store signalling take place
When Ca levels in the store are depleted - activates a receptor on the plasma membrane - this results in signalling from PLC - PIP2 - IP3, IP3 binds to receptors on the store to signal to SOCCs - they then open allowing Calcium to come into the cell - into the store
