Epithelial Transport

Question 1

The choroid plexus divides what two compartments?

Answer 1

cerebrospinal fluid (CSF) and blood

Question 2

The apical side of epithelia can also be referred to as…

Answer 2

luminal, or mucosal side

Question 3

The basolateral side of epithelia can also be referred to as…

Answer 3

interior, or serosal side

Question 4

Whate are the two pathways for passage of substances across an epithelial cell layer?

Answer 4

• paracellular (in between cells)

- transcellular (through cells)

Question 5

Tight junctions consist of what?

Answer 5

• a principal “barrier” protein, CLAUDIN

- a number of accessory proteins (including those that connect the tight junction to the cell’s cytoskeleton)

Question 6

Claudin isoforms are permselective for what?

Answer 6

Claudin isoforms can be permselective for cations (primarily Na+), anions (primarily Cl-), or have no charge preference. These pass through aqueous pores in the claudin.

Claudins limit passage of particles larger than 4-5 angstroms.

Question 7

Movement of glucose from filtrate leaving the glomerulus and being reabsorbed by the proximal tubule:

The energy for the movement of glucose from the filtrate across the apical membrane and into the cell comes from what?

Answer 7

The energy for this movement comes directly from that stored in the electrochemical gradient for Na across the luminal membrane

Question 8

Movement of glucose from filtrate leaving the glomerulus and being reabsorbed by the proximal tubule:

What transport protein is responsible for the coupled flux of Na and glucose in the early portion of the proximal tubule (cotransport via secondary active transport from lumen into cell across apical membrane)?

Answer 8

SGLT2

Question 9

Movement of glucose from filtrate leaving the glomerulus and being reabsorbed by the proximal tubule:

What transport proteins are responsible for the facilitated glucose transport across the basolateral membrane of renal tubules into the blood?

Answer 9

GLUT1 and GLUT2

Question 10

For net glucose transport to be sustained, what is necessary?

Answer 10

The Na-gradient must be maintained by action of an energy requiring system.
This is usually by primary active transport via the Na,K-ATPase

Question 11

In transepithelial transport of solutes (specifically glucose), what three types of carrier-mediated transport are involved?

Answer 11

• secondary active transport (Na-glucose cotransport across apical membrane)
• facilitated diffusion (Na-independent glucse transport across basolateral membrane)
• primary active transport (ATP dependent exchange of Na and K across the basolateral membrane) - this is ultimately responsible for energizing the sustained, net transepithelial flux of glucose

also worth noting is the leakage of K+ ions back out of the cell via channels

Question 12

The lumen of the proximal tubule, or of the small intestine, is essentially ___osmotic with the blood.

Answer 12

iso

therefore, no immediate driving force to promote an osmotic movement of water across the epithelial sheet of cells

Question 13

Transepthelial transport of water occurs via what mechanism?

Answer 13

Osmosis
There is a net movement of solute from the lumen to the blood, this causes a water gradient and a resulting net flow of “osmotically obligated” water from the lumenal to the blood side of the epithelium.

Question 14

In the duodenum and jejunem, the two principal routes for apical Na+ entry are:

Answer 14

• Na/H exchange

- Na-nutrient cotransporters

Question 15

How does transepithelial Cl- flux occur (what mechanism)?

Answer 15

paracellularly

Question 16

Transepithelial flux of Na+, Cl-, and water occur differently in the ileum. It involves the concerted activity of two parallel (in the same membrane) countertransport processes. What are these two processes?

Answer 16

• Na/H exchanger
• Cl/HCO3 exchanger

*both in apical membrane

Question 17

In the ileum, how does the Na/H exchanger work?

Answer 17

Na+ enters the cell, down its chemical gradient, and drives the efflux of H+ out of the cell into the lumen.

Question 18

In the ileum, how does the Cl/HCO3 exchanger work?

Answer 18

Cl- enters the cell, down it schemical gradient, which drives the efflux of HCO3- out of the cell into the lumen

Question 19

What is formed by the increase in the lumen of H+ and HCO3-?

Answer 19

they lead to the spontaneous formation of the free acid H2CO3, which in turn dissociates into CO2 and H2O (enhanced by the activity of the enzyme, carbonic anhydrase, found in the luminal, brush border membrane)

Question 20

After the formation of H2CO3 in the lumen due to the increase of H+ and HCO3- concentrations, what does H2CO3 dissociate into?

Answer 20

dissociates into CO2 and H2O (enhanced by the activity of the enzyme, carbonic anhydrase, found in the luminal, brush border membrane)

Question 21

Is the cell membrane permeable to CO2?

Answer 21

the cell membrane is very permeable to CO2 (and other gasses), so CO2 diffuses into the cell across the luminal membrane

Question 22

The rise in cytoplasmic CO2 leads to the formation of what?

Answer 22

H2CO3 (again facilitated by a cytoplasmic pool of carbonic anhydrase), which in turn, results in the regeneration of free H+ and HCO3-

Question 23

What happens to the Na+ and Cl- in the cytoplasm? How does water follow?

Answer 23

• Na+ leaves the cell via Na,k-ATPase in the basolateral membrane
• Cl- “follows,” it is unclear how exactly, possibly a channel in the basolateral membrane
• water follows by osmosis

Question 24

Is the osmotic flux of water transcellular or paracellular?

Answer 24

Mostly accepted to be transcellular. Water flows through aquaporin water channels.

Question 25

What are two aquaporins of particular interest?

Answer 25

• AQP1: widely distributed in cells including apical and basolateral membrane of proximal tube cells; appears to be constitutively active, present in membrane and effectively open all the time
• AQP2: more restricted distribution (e.g. principal cells of renal collecting duct); its insertion into the apical membrane is under tight regulation, thus permitting the apical membrane of these cells to shift from being effectively water impermeant to water permeant - this is important role in production of concentrated urine

Question 26

What is the most common strategy for the epithelial secretion of salt and water?

Answer 26

Involves basolateral cotransporter that moves 1 Na+, 1 K+, and 2 Cl- ions into the cell by a single, coupled transporter (Na,K,2Cl-cotransporter, or NKCC)

• this electroneutral process allows Na+ and Cl- to enter the cell down their chemical gradients
• K flux is against its chemical gradient, which serves as a check valve of sorts, preventing too much Cl- from coming in

Question 27

What is the result of Cl- entering the cell?

Answer 27

• intracellular Cl- concentration that can reach 50 mM
• this is still less than extracellular [Cl-] of about 100 mM, but it is well above the Cl- equilibrium distribution (which should be closer to 10 mM)
• because the inside of the cell is electronegative, Cl- will spontaneously exit the cell, given a ‘way out’ (via Cl channels in apical membrane; Cl- leaves the cell down its electrochemical gradient)

Question 28

How does Cl- leave the cell via the apical membrane into the lumen?

Answer 28

because the inside of the cell is electronegative, Cl- will spontaneously exit the cell, given a ‘way out’ (via Cl channels in apical membrane; Cl- leaves the cell down its electrochemical gradient)

Question 29

What change in Cl- secretion occurs in Cystic Fibrosis?

Answer 29

• in the secretory cells of the intestine, pancreas, liver, and gall bladder, the major Cl- channel in apical membranes is the same process that, when it fails, is the basis for development of cystic fibrosis: the Cystic Fibrosis Transmembrane conductance Regulator (CFTR)
• the opening of the CFTR Cl- channel is regulated by cytoplasmic concentration of cAMP (different Cl- channels in other tissues are regulated by cytoplasmic Ca2+ concentration)

Question 30

In secretion of salt and water, what happens to Na+?

Answer 30

Na+ enters through the basolateral membrane via the Na,K,2Cl-cotransporter (NKCC) down its electrochemical gradient. It then exits via the Na,K-ATPase in the basolateral membrane back into the blood. The transfer of Cl- transcellularly causes the Na+ to follow paracellularly from the blood to the lumen.

Also worth noting:

• water then is osmotically obligated to follow via aquaporins transcellularly from the blood to the lumen
• K+ that came into the cell via NKCC leaves back out the basolateral membrane into the blood via K+ channels (promotes the intracellular negative membrane potential)