Flashcards in 4. ATP-dependent Pumps and Ion Exchangers Deck (17):
How is [Ca2+]i controlled?
Using primary active transport: PMCA expels Ca2+ out of the cell (high affinity, low capacity), SERCA accumulates Ca2+ into the SR/ER (high affinity, low capacity).
Secondary active transport: NCX (low affinity, high capacity).
Facilitated transport: mitochondrial Ca2+ uni ports (buffers high concentrations).
How does the sodium calcium exchanger work?
Exchangers 3Na+ in for 1Ca2+ out, this makes it electrogenic with current flowing in the direction of the Na+ gradient.
What happens to the sodium calcium exchanger as the membrane depolarises?
It reverses in action as there is high [Na+]i and low [Ca2+]i so Na+ is pumped out and Ca2+ is pumped in.
How does the sodium calcium exchanger respond in ischaemia?
Ischaemia means ATP is depleted so the sodium pump is inhibited and Na+ accumulates inside and depolarises the cell. So the sodium calcium exchange reverses, if Ca2+ levels get too high, it can be toxic.
How is cell pH controlled?
Acid extruders - Na+H+exchanger, extrudes acid from the cell, Na+ dependent Cl-/HCO3- exchanger, brings in base and extrudes acid.
Base extruders - Cl-/HCO2- exchanger, extrudes base and brings in acid.
What is the function of the Na+H+ exchanger?
Exchanges H+ (goes out) for Na+ (enters). It regulates pHi and cell volume.
What is the Na+H+exchanger activated and inhibited by?
Activated by growth factors. Inhibited by amiloride.
What are the bicarbonate transporters and what is their role?
Na+ bicarbonate chloride contras porter alkalinises cell.
Anion exchanger acidifies cell.
They regulate cell volume.
What is the basic principle of cell volume regulation?
Move an osmotically active ion, water follows it. If the ion is extruded, the cell shrinks. If the ion is influxes, the cell swells.
What mechanisms resist cell swelling?
Conductive systems: K+ channel and Cl- channel.
Anion exchange brings in HCO2-, which joins with H+ from K+/H+ exchanger, to form H2CO3. This breaks down into H2O and CO2 which are extruded.
Exit of amino acids and K+ and Cl- means water leaves too.
What mechanisms resist cell shrinking?
Entry of Na+ and Cl-, Na+ K+ and 2Cl-, Na+ and organic osmolytes so H2O enters.
Entry of Na+ and Ca2+ through channel so H2O enters.
Exit of HCO3- and H+, entry Cl-, Na+ and CO2. Water enters and forms H2CO3 which breaks down into HCO3- and H+ which exit the cell.
How do loop diuretics affect the thick ascending limb of the kidney reuptake of Na+?
It stops the Na+ K+ 2Cl- exchanger transporting molecule. This means less water leaves the lumen of the thick ascending limb. Also less K+ and Cl- enter the capillary so less water moves in. THis leads to a lower BP.
How do thiazide and amiloride affect Na+ reuptake by the distal convoluted tubule of the kidney?
Thiazides block the Na+Cl- cotransporter. Amiloride inhibits ENaC. This means less Na+ and Cl- leaves lumen of the the distal convoluted tubule.
How do aldosterone, sprionolactone and amiloride affect the Na+ reuptake of the cortical collecting duct of the kidney?
Aldosterone up regulates ROMK and ENaC so more K+ and Na+ enter the lumen of the cortical collecting duct. Spironolactone blocks ROMK. Amiloride blocks ENaC.
Generally, how do diuretic drugs work in the kidney to reduce BP?
One or more Na+ reabsorption mechanisms are blocked by the diuretic drugs. This increases Na+ excretion and produces a hyper osmotic urine and the excretion of water.
How can [Ca2+]i be raised?
Facilitated diffusion - receptor-operated Ca2+ channels (ROC), voltage-operated Ca2+ channels (VOCC), IP3-gated Ca2+ channels (IP3R), Ca2+ induced Ca2+ release (CICR), store-operated Ca2+ channels (SOC), mitochondrial Ca2+ uni porters.
Secondary active transporters - Na+Ca2+exchange in reverse mode with depolarised cells.