ATP-dependant Pumps And Ion Exchangers Flashcards
What are the functions of NaKATPase?
- Forms Na and K gradients which are necessary for electrical excitability. But, it only contributes about 5mV to the resting membrane potential.
- It drives secondary active transport.
What things does secondary active transport regulate?
- Control of pH
- Regulation of cell volume and [Ca2+]
- Absorption of Na in epithelia
- Nutrients uptake eg glucose or amino acids from the small intestine.
What transporters are used to control the resting concentration of calcium? How?
- NCX (Na+-Ca+ exchanger) - this is a secondary active transporter because it does not require ATP. It has low affinity, high capacity and removes most of the calcium from the cell.
- PMCA (Plasma membrane Calcium ATPase) - this removes residual calcium out of the cell because it is high affinity, low capacity. It is a primary active transporter and also moves H+ in.
- SERCA (sarco(endo)plasmic reticulum Calcium ATPase - this moves residual calcium into the sarcoplasmic reticulum and is high affinity, low capacity. This is also a primary active transporter which moves H+ out of the sarcoplasmic reticulum (opposite to Ca).
- Mitochondrial Calcium uniports - these operate at high calcium concentrations to buffer the potential damage.
What happens if the concentration of calcium in a cell gets too high?
Calcification. This occurs because there are lots of phosphate molecules in cells so, CaPO4 forms which is a ppt. Calcium can also form CaCO3 which is another ppt. This ppt is dangerous because all reactions occur in solution in a cell.
How does the sodium calcium exchanger work?
- It’s role is to expel intracellular Ca during cell recovery (after muscle contraction)
- it exchanges one Ca for 3 Na
- Electrogenic - the current flows in the direction of the Na gradient (net change in charge across membrane).
- Causes depolarisation (make it more positive inside cell).
What happens or the Sodium Calcium exchanger(NCX) if cell is depolarised?
The ions move in the opposite direction to normal (reversed mode of operation). So, Na moves out of the cell while Calcium moves in.
What role does NCX play in ischaemia?
Ischaemia is when blood is flowing slower than expected to an organ so, it receives less oxygen than normal so heart works harder. (More anaerobic respiration -only glycolysis- so not enough ATP for muscle contraction)
This lack of ATP causes reversed mode of operation (Na moving out and Ca in) because NaKATPase cannot pump Na in and create the electrochemical gradient needed for depolarisation so NCX does it
This means that more Ca goes into the cell than expected and becomes toxic. If length of time, calcium deposits appear in cardiomyocites. These calcium deposits are a sign of a myocardial infarction.
How is pH controlled inside a cell?
pH is controlled using Acid and Base Extruders.
Acid extruders: (move H+ out)
-Na+/H+ exchanger (NHE) -is a secondary active process. Causes cell to become more alkaline.
-Na+ dependant Cl-/HCO3- exchanger / NBC (sodium bicarbonate transporter). This moves Na and bicarbonate in and chloride and hydrogen ions out (HCl) . This is the best buffer in the body. If your blood is acidic (acidosis) then bicarbonate is used to neutralise.
Base extruders :
-Cl-/HCO3- exchanger - AE (anion exchanger) - Important in drug movement and in erythrocytes.
Describe the properties and role of the Na+/H+ exchanger.
- exchanges extracellular Na for intracellular H+
- Electroneutral (no change in charge)
- Regulates pH
- Regulates cell volume (water moves in with Na)
- Activated by growth factors
- Inhibited by amiloride (a potassium soaring diuretic). This is a hypertension drug.
What causes a change in cell volume?
When osmotically active ions (Na, K, Cl) or organic osmolytes (amino acids) are moved, water follows. This causes cell swelling end shrinkage.
Cell swelling is caused by an influx of ions so the best treatment is to extrude (remove) ions.
Cell shrinkage is causes by a lack of ions so, to treat you need an influx of ions.
There are 6 water molecules around every Na ion. If her Cs poisoning, you become Oedemic because each molecule = 36 water molecules.
What mechanisms resist cell swelling?
Conductive systems - as K and Cl move out then water follows
Cotransport system - as ions and amino acids move out, water goes with it
As choline moves out, bicarbonate moves in. Potassium also moves out and hydrogen moves in. The bicarbonate and hydrogen combine to form carbonic acid. This carbonic acid breaks down to form carbon dioxide and water which both leave and therefore reduce cell shrinkage.
What mechanisms resist cell shrinkage?
Use the opposite mechanisms to those which resist cell swelling.
Co-transport - NaCl co-transport or Na and organic osmolytes (amino acids). The movement in will take water with it.
Conductive systems - NaCa channels bring water in too.
In erythrocyte, carbon dioxide combines with water to form carbonic acid. Carbonic anhydrase then breaks this down into H+ (and Na) and HCO3 (Cl) which both leave the cell via antiport cotransport
What would happen if ions were not reabsorbed after filtration in the kidney?
Water would follow the Na and HCO3 our of the blood and your patient would rapidly dehydrate.
How does the kidney bring the ions back into the blood in the proximal tubule?
Sodium Bicarbonate is in ionic form in lumen.
Sodium goes into epithelial cells using NHE.
This bring H+ into lumen.
The H+ combine with HCO3- to form carbonic acid.
This carbonic acid is broken down into carbon dioxide and water using carbonic anhydrase.
Both CO2 and H2O go into epithelial cells and reform carbonic acid which is the broken down.
H+ goes bake to lumen and HCO3 goes into capillaries via an anion exchanger. (This takes Cl back into epithelial cells)
Na goes into capillary via Na K pump.
K goes back to lumen.
Cl goes into capillary via chloride channel.
What is renal control of Na conc a first lie treatment for?
Mild hypertension (high BP) by taking a water tablet (diuretic therapy) such as furosemide. Although first line treatment now is ace inhibitor or Ca tablet.
