Ion Transporter In Cell Physiology

Question 1

How is intracellular acidification (decreased pH) opposed by ion transporters?

Answer 1

• Na+/H+ exchanger (NHE) in some cells exchanges exchanges extracellular sodium for intracellular protons - acid extrusion.
• Na+/HCO3- cotransporter (NBC) in some cells exchanges extracellular sodium for intracellular protons - acid extrusion, and intracellular chloride for extracellular bicarbonate - alkali influx.

Question 2

How is intracellular alkalisation (increased pH) opposed by ion transporters?

Answer 2

• Anion exchanger (AE) in most cells exchanges extracellular chloride for intracellular bicarbonate - alkali extrusion.

Question 3

What drives the activity of intracellular pH-regulating ion transporters?

Answer 3

• The sodium gradient generated by Na+/K+ ATPase.

Question 4

How is cell volume regulated without affecting membrane potential?

Answer 4

• Electroneutral transport of ions (move 1 positive and 1 negative at the same time)
• Allows osmotic strength of the cytoplasm to be varied without effect on membrane potential

Question 5

How does ion transport change to regulate cell swelling?

Answer 5

• Cell swelling - efflux of osmotically active ions (Na+, K+ & Cl-) or solute molecules - water follows ions out of the cell - cell shrinks.

Question 6

How does ion transport change to regulate cell shrinking?

Answer 6

• Cell shrinking - influx of osmotically active ions (Na+, K+ & Cl-) - water follows ions into cell - cell swells.

Question 7

Which ion transport systems are used to regulate cell swelling?

Answer 7

• Conductive systems, e.g.
  K+ channel
  Cl- channel

- Cotransport systems, e.g.
   Amino acid transporter
   K+/Cl- symport
   Cl-/HCO3- antiport 
   K+/H+ antiport
(HCO3- and H+ react in the cell to form H2CO3 - excreted as CO2)

Question 8

Which ion transport systems are used to regulate cell shrinking?

Answer 8

• Conductive systems, e.g.
  Na+ channel
  Ca2+ channel

- Cotransport systems, e.g.
   Na+/Cl- symport
   Na+-dependent Cl-/K+ symport
   Na+/organic osmolyte symport
   Anion exchanger
   NHE

Question 9

Where does bicarbonate reabsorption in the kidney occur? Why is this important?

Answer 9

• Proximal tubule

- Retains base for pH buffering capacity

Question 10

Describe the reabsorption of bicarbonate in the proximal tubule of the kidney.

Answer 10

1. In the proximal tubule lumen, NaHCO3 is broken down into HCO3- and Na+.
2. HCO3- reacts with H+ to form H2CO3.
3. Carbonic anhydrase breaks down H2CO3 to H2O and CO2 which can diffuse across the lipid bilateral into the proximal tubule cell.

These processes are driven by the NHE, which drives the secondary active transport of H+ from the PT cell to the PT lumen using the Na+ gradient generated by the break down of NaHCO3.

4. In the PT tubule cell, Carbonic anhydrase allows H2O and CO2 to react, forming H2CO3.
5. H2CO3 dissociates into H+ (transported to PT lumen via NHE) and HCO3-.
6. HCO3- is transported to the capillaries via an AE which exchanges intracellular HCO3- for Cl-.

Question 11

Where does Na+ reabsorption in the kidney occur?

Answer 11

• Thick ascending limb
• Distal convoluted tubule
• Cortical collecting duct

Question 12

In which disease is renal control of circulating Na+ conc. important?

Answer 12

Mild hypertension: water follows Na+ so decreasing Na+ movement into BVs would reduce water content of BVs and thus decrease BP.

Question 13

Describe the reabsorption of sodium from the cortical collecting duct lumen.

Answer 13

There is a low intracellular Na+ concentration in the cortical collecting duct cell.

• 1Na+ can thus move by facilitated diffusion via ENaC from the CCD lumen into the CCD cell.
• The Na+/K+ ATPase can then pump 3Na+ (in exchange for 2K+) into the capillaries.

K+ is returned to the capillary or CCD lumen via ROMK (Renal Outer Medullary K channel).

Question 14

What is special about the transport of water from the collecting duct lumen and how is this endogenously controlled?

Answer 14

• Presence of aquaporin - specialised H2O channel which allows 5x faster movement of water.
• ADH (anti-diuretic hormone) increases expression of aquaporins. Production of ADH is inhibited by alcohol (diuretic).

Question 15

Which endogenous molecule enhances the movement of Na+ and K+ across cortical collecting duct cells?

Answer 15

• Aldosterone (part of the renin-angiotensin system) = primary mineralocorticoid enhancing expression of mineralocorticoid receptors (ENaC, ROMK and Na+/K+ ATPase).

Question 16

Which exogenous molecules (used in hypertension treatment) inhibit the movement of Na+ and K+ across cortical collecting duct cells?

Answer 16

• Spironolactone = mineralocorticoid receptor antagonist - TF which blocks production of ENaC, ROMK and Na+/K+ ATPase.
• Consequently: decrease Na+/K+ and H2O in capillary so decreased BP.
• Amiloride blocks ENaC - same effect.

Question 17

How do glucose transporters in intestinal epithelial cells transport glucose from the gut into the blood against the uphill concentration gradient for glucose? Which other part of the body utilises the same mechanism?

Answer 17

1. Na+/K+ ATPase in basal epithelial cell membrane exchanges K+ from blood for Na+ from epithelial cell - creates low [Na+]i.
2. Na+/glucose symporter in apical cell membrane transports 1 glucose from intestinal lumen into epithelial cell for every 2 Na+, using Na+ gradient generated by Na+/K+ ATPase. SECONDARY ACTIVE TRANSPORT
3. GLUT2 transporter in basal cell membrane allows movement of glucose from the cell into the blood via FACILITATED DIFFUSION.

• Kidney epithelial cells

Question 18

How does the uptake of glucose from the blood into adipose, brain, liver and skeletal muscle cells differ to that found in intestinal and kidney epithelial cells?

Answer 18

• Glucose conc gradient favours uptake so glucose enters by facilitates transport via glucose transporters (GLUT1-7 - different kinetic properties).
• In some cells, these transporters are not permanently within the plasma membrane, but need insulin to stimulate their translocation from the cytoplasm when specific glucose uptake is required.

Question 19

How does insulin stimulate the rate of glucose uptake into adipose tissue and skeletal muscle?

Answer 19

• Recruits GLUT-4 transporters from internal vesicular membranes to the plasma membrane to increase the transport capacity of the membrane.

Question 20

What prevents the efflux of glucose from cells in tissues (e.g. Adipose and skeletal muscle) when the circulating glucose concentration falls to resting levels in the post-absorptive period after a meal?

Answer 20

• Glucose is rapidly converted to glucose-6-phosphate on entering the cell by the actions of hexokinase in the liver and glucokinase in other cells.
• Thus, the intracellular glucose conc never rises high enough to reverse the conc gradient.

Question 21

Apart from glucose, what other metabolites use the sodium gradient for their uptake into cells against their conc gradient?

Answer 21

• Amino acids (family of known transporters for different groups of related amino acids).