Atp Dependent Pumps And Ion Echangers Flashcards
What are the functions of the Na+K+ ATPase
- Forms Na+ and K+ gradients
– Necessary for electrical excitability
– (only contributes about - 5 mV to the resting membrane potential)
2. Drives Secondary Active transport – Control of pHi – Regulation of cell volume and [Ca2+]i – Absorption of Na+ in epithelia – Nutrient uptake, e.g. glucose or amino acids from the small intestine
Give a summary of the control of resting [Ca2+]i
• Primary active transport
– PMCA expels Ca2+ out of the cell
• High affinity, low capacity (removes residual Ca2+)
– SERCA accumulates Ca2+ into the SR/ER
• High affinity, low capacity (removes residual Ca2+)
• Secondary active transport
– Na+-Ca+-exchange (NCX)
• Low affinity, high capacity (removes most Ca2+)
• Facilitated transport
– Mitochondrial Ca2+ uniports
• Operate at high [Ca2+]i to buffer potentially damaging [Ca2+]
What is the role of the NCX?
- Role in expelling intracellular Ca2+ during cell recovery
- Exchanges 3 Na+ for 1 Ca2+
- Electrogenic – current flows in the direction of the Na+ gradient
- Possible role in cell toxicity during ischaemia/reperfusion
What is NCX activity dependent on?
Membrane potential
Depolarisation of membrane- changes orientation of exchanger
Then exchanges calcium - moves it back in - not good as calcium is toxic to cells
What does the NCX do in ischaemia?
If blood vessels close down blood flow is restricted - ischaemia - blood not flowing
Infarction = stop bs moving
Depletion of atp in tissue
Na/K pump needs atp to be hydrolysed so cannot push sodium out
Na/Ca exchanger needs Na in to push ca out
Depolarisation - exchanger is now doing opposite - doing job of sodium pump
BUT moving calcium in -
High ca in becomes toxic
Ca deposited in tissue
In patients w/ myocardial infarction, Ca deposits inside myocites
How is cell pH controlled?
Acid Extruders
Na+/H+ exchanger - NHE
Drives protons out so cells become more alkaline
Na+ dependent Cl-/HCO3- exchanger NBC (sodium bicarbonate cotransporter) - moves Na and HCO3 in (best buffer), HCl moves out
Base Extruders
Cl-/HCO3- exchanger -
AE (anion exchanger)
Very important in movement of drugs
What is the function of the NHE
• Exchanges extracellular Na+ for intracellular H+ • Electroneutral 1:1 exchange • Regulates pHin • Regulates cell volume • Activated by growth factors • Inhibited by amiloride (a potassium sparing diuretic)
What are the bicarbonate transporters?
Na+ bicarbonate chloride cotransporter NBC - H+ and CL- out, Na+ and HCO3- in
Alkalinises cell
Anion exchanger Band 3 - acidifies cell - HCO3- out Cl- in
Extruding hydrogen and chloride In peripheral capillary co2 enters rbc Only 1% traces in Hb - most in HCO3- Can exchange with chloride ion in band 2 co trabnsporter Causes ph change (decrease) Affect structure of Hb Release oxygen Exchaneges CO2 for O2
What ion transports regulate cellular pH
Na K ATPase - ALL CELLS - creates Na+ gradient to provide energy for following transporters
Na H exchange - MOST CELLS - Acid extrusion
Na+/Cl-/HCO3-/H+ co transport (NBC, coupled Na+-H+ and anion exchange) - SOME CELLS - Acid extrusion and alkali exchange
Na+/HCO3- co transport - SOME CELLS - alkali influx
Anion exchange Band 3, AE - MOST CELLS - alkali extrusion
How is intracellular pH regulation co ordinated?
pH is held at the set point. Any drift away from this pH is corrected by the increased activity of either the Na+-H+- or Cl–HCO3- exchangers
If cell becomes too acidic Na/H exchanger brings Na back up
Heteostasis
Hypertension - new homeostatic point
Modulates around this point to get to normal range
Water and Na levels need to be altered
How is cell volume regulated?
- Transport of osmotically ‘active’ ions, e.g. Na+, K+, Cl- or organic osmolytes (amino acids) out of cell
- Water follows
- Cell swelling – extrude ions
- Cell shrinking – influx ions
What are 3 ways to resist cell swelling
Efflux of osmotically active ions K+ and Cl- via conductive systems, H2O follows
Efflux of osmotically active ions K+ and Cl- and AAs via cotransporter systems, H2O follows
Chloride leaves, HCO3- enters
K+ leaves, H+enters
H+ and HCO3- form H2CO3, splits into CO2 and H2O, H2O leaves
Outline 3 mechanisms to resist cell shrinking
Influx of osmotically active ions (Na+ K+ Cl-) via conductive systems, H2O follows
Influx of osmotically active ions (Na+ K+ Cl-) via cotransport systems, H2O follows
H2CO3 dissociates Into HCO3- and H+, these leave in exchange for Cl- and Na+ respectively, water and CO2 enter to make H2CO3
Describe bicarbonate reabsorption by the PCT
- If filtration occurred on its own
- Then Na+ and HCO3- ions would leave the body
- H2O would also go too and your patient would rapidly dehydrate
Nahco3 in ionic form
Na in epithelial cell
Na pump pumps sodium out and k+ in, K out through K+ channels
Remove Na from duct into blood stream
HCO3- binds with hydrogen and makes carbonic acid, acted by carbonic anhydrase
Produces water and CO2
Acted on by carbonic anhydrase
Dissociates into H+ (for NA/H+ exchanger)
Bicarbonate ion needs to get intto bloodstream
Via AE, brings CL- in
Cl- out through chloride channel
What can renal control of circulating Na+ conc be used as a treatment of?
- Here’s an example:
- Renal control of circulating Na+ concentration is often a first line treatment for patients with mild hypertension
- The ‘water tablet’ or diuretic therapy
Describe Na+ reuptake by the kidney
Na/k/di chloride so transporter moves everything into epithelial cell K/cl hits surface, co transporter moved both Chloride channel moves cl- All driven by sodium potassium pump ROMK put k+ back into lumen Loop diuretics block symporter Take water with them Reduces blood pressure
