Cell Homestasis Flashcards
What does the thick ascending limb of the loop of Henle do?
It reabsorbs sodium chloride in preference to water
This creates a transepithelial osmotic gradient which is responsible for the counter current multiplication later seen in the collecting duct
What is the sodium concentration typically outside of a cell?
145 mil mol
What does the NKCC in the loop of henle depend on?
It depends on the inward movement of sodium into the loop of henle
What happens if sodium levels inside of the cells at the loop of henle become too high?
Then sodium chloride absorption at the thick ascending limb decreases in the cell.
What happens if the transepithelial osmotic gradient is dissipated (abandoned)?
remember this is when water wasnt absorbed in the thick ascending limb of the loop of henle to make an osmotic gradient which would move water into the collecting duct. Instead sodium chloride was absorbed.
You would have an increase in levels of urine and increase sodium chloride moving into the urine. As the Na Cl wouldnt be absorbed at the ascending limb.
What is the normal voltage of sodium inside the cell, its nernst potential, the membrane potential of a excitable cell in general and how much sodium is usually found outside the cell
Sodium inside the cell = 15 mv
Nernst potential = +60mv
Vm = +70mv
Sodium outside of cell = 145 mv
Electrical gradient of sodium is largely into the cell.
What would be the effect of sodium voltage inside the cell increasing from 15 to 45mv? And what is the problem with this?
The nernst potential of the sodium becomes +30mv which keads to a decrease in electrical gradient
This would causes an issue with action potential
This leads to a slower conduction of the action potential.
Sodium potassium ATPase? What does it extrude? And is the NAKCC channel in the ascending limb of the loop of henle a pump?
3 sodium ions coupled to 1 hydrolysed ATP
No the NaKCC channel is not a pump. It doesnt need ATP
The specifics - how does the sodium potassium ATPase actually work? As in what happens with sodium, calcium and potassium
ATP binds to the pump (this forms ADP)
The pump is now phosphorylated
Sodium already bound to the pump, then dissociates from the pump.
In the next stage calcium enters and binds to the the cleft of the pump
Potassium then binds, exposing the cleft of the pump to the inside of the cell. This causes the pump to undergo a CONFORMATIONAL change. Potassium then enters the cell.
The turnover rate of the sodium potassium ATPase pump depends on?
ATP levels
What inhibits the sodium ATP pump?
It is inhibited by cardiac glycosides - ouabain and digoxin
They can stop the pump from dephosphorylating
What is the role of the ATPase?
Controls membrane potential
Net effect makes cell more negative inside
Allows potassium to accumulate in the cell so it can be used in the hyperpolarisation stage of an action potential = cell is more negative.
In the collecting duct. Amiloride sensitive channels are found on the apical membrane of the epithelial cells. Where is the sodium potassium pump found?
On the basolateral membrane
This allows sodium to be transported right across the cell from the lumen of the intestines right to the basolateral membrane and then into the blood.
Why is calcium regulation in cells important. And what in the general amount inside and outside of the cell?
There is usually 100nM inside the cells
In the extracellular is usually 1x10^6 nm
Calcium must be regulated in the cell because its an important second messenger. E.g. in pancreatic fusion cells
How do we keep calcium levels in the cell keep low and why do we use this method?
We use the sodium calcium exchanger and active calcium pumps to move calcium out
This is because gradients favour calcium entering the cell. Remember voltage gradients move from higher to lower voltages. And calcium outside the cell is at +120 mv so it wants to move into the cell where the voltage of calcium is lower.
How does the sodium calcium exchanger work?
3 sodium move in and 1 calcium moves out
At equilibrium what is the equation for the sodium calcium exchanger?
[ca outside]/ [ca inside] = ([Na outside] /[Na inside])3 x (water potential out - water potential outside / 60
Water potential is represented by a trident
What family is the calcium exchanger part of? What are the three forms of this exchanger in mammals?
It is part of the SLCB gene family
There is the P type:
- The PMCA - plasma membrane calcium pump
- This acts to pump calcium across the plasma membrane and out of the cell
There is SERCA
- PUMPS found on the sarcoplasmic reticulum/ endoplasmic R
- this pumps calcium out of the cytoplasm into organelle which act as calcium stores.
The SPCA:
- this is a calcium pump found on the golgi apparatus
- also transports Mn2+
How do the three types of calcium pump work?
Calcium binds to the pump
So does ATP
Shape of protein changes
It then is exposed to the other side of the cell membrane
The pump is then dephosphorylated - ADP leaves
All pumps keep calcium levels in the cytoplasm low allowing for a calcium gradient from outside the cell to in.
What are the channels involved in calcium movement? 4 types?
Voltage operated calcium channels VOCC
- These are found in excitable cells activated by depolarisation
- due to a voltage calcium enters
Receptor operating calcium channels
- found in secretory cells and nerve terminals activated by the binds of an agonist. E.g. NMDA receptor.
Mechanical activated Ca channels
- found in many cells and respond to cell deformation - example is stretch activated channels
This may activate the caclium mediated channel
Store operated calcium channels:
- activated following the depletion of calcium stores. These are in the cells membrane helping the calcium stores replenish their stocks.
What are the two receptors in the endoplasmic reticulum (Which store calcium) help with the release of calcium?
IP3 receptors - these are activated by IP3 2nd messenger
Ryanodine receptors: AGAIN these release calcium
- lower levels of ryanodine active these channels whereas higher levels inhibit this receptor. This channel is also stimulated by caffine
- the natural activator of this channel is cADP ribose and these channels are found in excitable cells
What are SOOC’s and what do they do?
These are store operated calcium channels - they work to move calcium back into stores
They are located on the calcium stores
What is the pathway which activates SOOCs?
Note SOOCS are found on the ER membrane and are activated to bring calcium back in!
A receptor is stimulated on the calcium stores membrane e.g. the ER’s membrane
- this causes the stimulation of phospholipase C
Ip3 then goes onto activate the receptor on the ER
Calcium moves out into the cytoplasm
The loss of calcium is detected and signals are sent to the stores membranes which causes calcium to move back in.
How is calcium also released with the help of stim proteins?
Note these stim 1 proteins are calcium binding proteins found in the membranes of calcium stores such as the ER
When the store is activated it changes binding of STIM 1 and calcium
This causes STIM1 to change its shape and cause the release of calcium which it was originally bound to from the ER into the cytoplasm via CRAC channels - calcium release activated channels
How is calcium reuptaken from the extracellular fluid via stim 1 and orai channels?
Stim 1 proteins move the ER to the cell plasma membrane - it drags the ER membrane to the plasma membrane
The stim 1 proteins and ORAI channels interact - calcium moves into the cell via the Orai channels
Calcium then moves straight into the stores of the ER thanks to stim 1 proteins
