Epithelial Transport

Question 1

Where is the apical surface of the epithelium lining?

Answer 1

Faces the “special” fluid ((e.g.; food in the gut; urine in the kidney; saliva in the parotid duct). AKA mucosal; lumenal

Question 2

What type of transporters are seen in the apical surface?

Answer 2

Usually contains the special transporters that endow the epithelium with its specialized transport properties.

Question 3

Where is the basolateral surface of the epithelium lining?

Answer 3

Exposed to the interstitial fluid. AKA serosal peritubular

Question 4

What type of transporters are seen in the basolateral surface?

Answer 4

Usually has generic transport properties like the plasma membranes of non-epithelial cells

Question 5

If a substance needs to get across the epithelium; which two pathways may it follow?

Answer 5

May either cross two membranes by entering the epithelial cell on one side and leaving on the other; OR it may cross no membranes at all by passing in between cells through the pericellular shunt pathway (“leaky” tight junctions).

Question 6

What is the driving force for MOST transport (water;salt;nutrient;non-volatile metabolic wastes)? Where is it located?

Answer 6

Na/K pump. ALWAYS located in the basolateral membrane

Question 7

What does keeping intracellular Na concentration low do?

Answer 7

By keeping intracellular sodium ion concentration low; the Na/K pump provides the energy to drive a host of secondary transporters

Question 8

What is the main exception to universal dependence of epithelial pumping on the Na/K pump? Why?

Answer 8

Protons. Because primary active transporters have evolved for protons (most notably in the stomach (to secrete acid into the lumen of the stomach) and kidney (to excrete protons - a metabolic waste product.)

Question 9

With respect to permeability; membrane potential; etc.; which membrane is most like a normal cell?

Answer 9

The basolateral membrane (relatively low sodium permeability/high potassium permeability. Membrane potential = -70 mV).

Question 10

How is the apical membrane different than the basolateral membrane with respect to permeability/membrane potential?

Answer 10

Is relatively highly permeable to sodium; not potassium. Vm is more positive; close to +10 mV. NO Na/K pump in the apical membrane

Question 11

How are salt & water transported from apical to basolateral solution (when tight junctions are tight)?

Answer 11

Sodium ions leak into the cell across the apical membrane (down their electrochemical gradient). They are then pumped out of the other side of the cell by the Na/K pump (across the basolateral membrane). Results in the net transport across the epithelium of a positive charge. Chloride follows passively; drawn by the electrical force. The net transport of NaCl produces an osmotic gradient (draws water along).

Question 12

If one were to measure the voltage across this epithelium; what would be the result?

Answer 12

The apical solution is negative with respect to the basolateral solution.

Question 13

What would happen to the transepithelial voltage if the chloride ions in the apical solution were replaced with a larger anion that could not fit through the chloride channel?

Answer 13

The Na/K pump would continue to operate. Because no anion can follow; the transepithelial voltage will increase. Soon the apical solution would become so negative that net sodium transport would stop.

Question 14

How do you calculate the transepithelial potential difference (transPD)?

Answer 14

TransPD = Vm (Basolateral) - Vm (Apical)

Question 15

What three rules must be used to calculate transPD?

Answer 15

i) all membrane potentials are written as the potential of the inside of the cell with respect to the outside (i.e.; outside = zero); ii) the transepithelial potential is written as the potential of the apical solution with respect to the basolateral (i.e.; basolateral = zero); iii) the cell is isopotential (all voltage drops are at membranes ? no change over distance; except across membranes).

Question 16

What are the main differences with water/salt movement across the epithelium when tight junctions are leaky?

Answer 16

Major difference is that the leaky epithelium is usually capable of moving a larger amount of material. 2 - leaky tight junctions partially short-out the transepithelial potential difference; a lower transepithelial voltage is measured. 3 - Chloride and water follow the shunt pathway instead of passing through the membrane.

Question 17

In the loop of Henle (kidney) and respiratory tract the apical sodium channel is replaced with what?

Answer 17

An electroneutral cotransporter. Carries 1 potassium; one sodium; two chloride ions into the cell each cycle.

Question 18

What channel drives epithelial secretion? Where is it?

Answer 18

A chloride channel in the apical membrane

Question 19

In a resting cell; is the Cl- channel in the apical surface open or closed?

Answer 19

Closed

Question 20

What happens when the Cl- channel is activated? How does this work?

Answer 20

Begins to secrete electrolytes and water into the lumen. Cl- is pumped into the cell across the basolateral membrane (by a Na-K-2Cl cotransporter) and leaks out the other side through a Cl- channel. As the Cl- leaks into the lumen; electrical negativity that it creates draws Na+ along passively (Na+ flows mostly through the intercellular shunt pathway). Resulting osmotic gradient draws water along; giving a net secretion of an isotonic solution of NaCl

Question 21

What is the state of Cl- channels during secretion? During absorption?

Answer 21

At rest the apical Cl- channels are closed; so absorption wins. When Cl- channels are opened; secretion wins

Question 22

How is secretion turned on during digestion?

Answer 22

Parasympathetic nerve stimulation leads to hormones in the blood. In the GI tract chemicals activate receptors in the basolateral membrane. Signal is carried across insdie of cell to apical membrane by cell signaling mechanisms (Ca++ ions; activated protein kinases; cyclic AMP; etc.)

Question 23

How does cholera toxin work?

Answer 23

By locking open the Cl- channels causes a massive efflux of fluid from the cell. Leads to profound diarrhea and dehydration. Toxin secreted by Vibrio cholerae.

Question 24

What is the specific Cl- channel that is important in cystic fibrosis?

Answer 24

Cystic Fibrosis Transmembrane Conductance Regulator (CFTCR or commonly CFTR)

Question 25

How does cystic fibrosis work?

Answer 25

CFTR channel is mutated. Reduces the ability of epithelia to secrete serous (watery) fluid. Leads to thickened mucous secretions; infections; and other lifeshortening complications.

Question 26

How does epithelial absorption of sugars/amino acids work in the GI tract and kidney?

Answer 26

Solutes are pumped into cells via a secondary active transporter which is driven by the inward sodium leak. The solutes diffuse across the cell and are transported down their energy gradient out of the cell across the basolateral membrane by way of facilitated diffusion. Na+ is pumped out of cell by Na/K pumps in basolateral membrane

Question 27

How is most (14.5 out of 15 moles) of metabolic waste gotten rid of?

Answer 27

As CO2 (the end product of carbon metabolism). A volatile molecule; it is simply exhaled via the lungs

Question 28

What type of waste does the kidney get rid of?

Answer 28

Non-volatile metabolic waste. Most is the end product of nitrogen metabolism (urea). Most of the remained are protons.

Question 29

What does the kidney have to do to get rid of urea since we don’t have urea transporters?

Answer 29

It forms an ultrafiltrate of plasma (contains water; salts; sugars; amino acids; etc. plus the non-volatile metabolic waste products) in the glomerulus. As this plasma ultrafiltrate passes along the renal tubules; the epithelial cells lining the tubules reabsorb (pump back into the blood) the things that it wants to keep; allowing the wastes to pass on. Requires a lot of ATP

Question 30

What else does the kidney do (in addition to excreting non-volatile metabolic wastes)? Why does it have to do this?

Answer 30

Regulates the ECF composition by adjusting the activity of the transporters that do the reabsorbing. Has to do this bc the GI tract absorbs everything regardless of the needs of the ECF.

Question 31

How does the kidney get rid of extra water?

Answer 31

The epithelium is made water impermeable so water cannot follow the solutes out of the lumen.

Question 32

How is the epithelium made impermeable to water?

Answer 32

The hypothalamus detects a drop in plasma osmolarity and stops secreting anti-diuretic hormone (vasopressin). Causes kidney epithelial cells to remove aquaporins from their apical membranes.

Question 33

Describe the basic 3 steps of water conservation

Answer 33

1. NaCl is pumped out of the tubule; water cannot follow; the interstitium is not well vascularized so that the salt raises the osmolarity there. 2. Water is removed passively in the distal tubule (5/6 of the water is removed here) 3. More water is removed in the collecting duct. Produces a hyperosmotic output (urine)