Lecture 8: Transports of Solutes and Water Across Epithelia

What is the epithelium?

a sheet of cells joined together by junctional complexes

What is the function of the epithelium?

• form a dynamic barrier that can import or expel substances

• protect internal environment from the external world

What is the apical membrane?

faces lumen of compartment continuous with outside world

What is the basolateral membrane?

faces extracellular fluid, rests on basement membrane

What is the basement membrane composed of?

extracellular matrix proteins produced by epithelial cells themselves

What are some examples of matrix proteins?

• collagens

• laminin

• proteoglycans

What is the function of the basement membrane?

provide structural support for the epithelium

What are the two different pathways for substances to cross the epithelia?

• transcellular pathway: through the cell

• paracellular pathway: around the cell

What type of transmembrane proteins do tight junctions contain?

claudin and occludin

What do tight junctions do?

create a diffusion barrier

True or False: Zonula occludin 1 is an example of an intracellular protein in tight junctions that help to stabilize the complex and provide intracellular signaling roles (such as links to serine/threonine kinases).

true

True or False: Tight junctions in epithelia impede the passage of molecules and ions between cells of epithelial monolayer.

true

What are the functions of tight junctions in epithelia?

• help to maintain cell polarity

• cell-cell adhesion

What is each tight junction comprised of?

parallel strands of transmembrane proteins

What is the degree of epithelium’s impermeability proportional to?

the number of strands of tight junctions

True or False: Permeability can be modulated in response to physiological stimuli.

true

What is the main structural element in epithelial tight junctions?

claudins

What type of interactions do adhering junctions have?

Ca²⁺-dependent interactions of cadherins

What does cadherin clustering lead to?

intracellular catenin clustering

Adhering junctions are sites of attachment for what?

the actin cytoskeleton

What role do adhering junctions play in organ development and remodeling?

• disruption of adhering junctions leads to B-catenin dissociating from cadherin

• increase in free B-catenin and translocation to the nucleus

• changes in gene transcription

Briefly describe adhering junctions in epithelia.

a belt that encircles the entire epithelial cell, just below level of tight junction

In adhering junctions, cell-cell contacts are mediated by what?

cadherins (extracellular domains)

True or False: Adhering junction formation triggers intracellular cytoskeleton assembly. The cytosolic domains of cadherins link to network of actin filaments.

true

What are gap junctions?

channels that interconnect the cytosols of neighboring cells

What type of molecules do gap junctions allow to pass through? What is this based on?

small molecules and ions (based on electrical coupling)

True or False: Permeability can be regulated in epithelia gap junctions.

true

What do demosomes do?

hold adjacent cells together tightly at single spots

What are desmosomes mediated by?

extracellular domains of desmoglein or desmocollin (types of cadherins)

What links cytosolic domains to intermediate filaments?

anchor proteins (plaques)

What do anchor proteins couple?

couples structurally stabilizing elements of neighboring cells to each other

True or False: Epithelial cells are polarized and membrane morphology increases surface area.

true

What is the apical and basolateral surface area amplified by?

• apical: brush border

• basolateral: smaller infoldings (area amplified to a lesser extent)

Describe the brush border.

• hundreds of microvilli projections

• membrane-bound enzymes that break down sugars, peptides restricted to the apical membrane

True or False: The ECF and outside world have different ion/solute compositions—creating a difference in transepithelial concentrations.

true

True or False: The electrochemical gradients across the apical and basolateral membranes differ.

true

What is transepithelial voltage?

the voltage difference between solutions on either side of the epithelium

How is transepithelial voltage measured?

electrode #1 in the lumen of organ or duct, electrode #2 in interstitial space/blood

What is the equation for transepethelial voltage?

V_bl - V_a = V _te

What is transepithelial resistance?

the measure of how tightly epithelium separates compartments, based on ease of flow of electrical current

What does low electrical resistance equate to?

low-resistance pathway in tight junctions (current flows more easily)

Which side of the membrane is the Na/K only on?

the basolateral side

True or False: Extrusion of Na by the Na/K pump lowers intracellular sodium concentration and creates an inward gradient for sodium on the apical side.

true

Na enters passively through apical what?

ENaC channels

True or False: The lumen-negative transepeithalial voltage provides a driving force for passive Cl- absoprotion in the paracellular pathway.

true

True or False: NaCl is absorbed into the interstitial space.

true

What happens to most of the K taken up by the Na/K pump?

most is recycled back across the basolateral membrane into the interstitial space via K+ channels

True or False: Some epithelial cells also express K+ channels on the apical membrane such as the collecting tubules of the kidney.

true

Inward Na+ electrochemical gradient on the apical side drives uptake of Na+ through what?

the Na-glucose cotransporter

Glucose exits passively across which membrane via the glucose transporter (GLUT)?

basolateral membrane

True or False: Lumen-negative transepithelial voltage is generated—driving passive Cl- absorption into the interstitial space (net NaCl and glucose absorption).

true

Inward Na electrochemical gradient drives secondary active Cl- uptake by what on the basolateral membrane?

by NKCC

How does Cl- exit passively across the apical membrane?

through Cl- channels

True or False: The negative charge entering the lumen (aka Cl) attracts passive Na+ entry into the lumen (paracellular). The net effect is NaCl.

true

Epithelial H₂O permeability varies widely due to which factors?

• membrane lipid composition

• AQP expression

If the lumen and interstitial have similar osmolarities, how do you get H₂O flux across the epithelium (2 possibilities)?

• high constitutive AQP expression: small differences in osmolarity would be sufficient to drive H₂O flux

• modest hyperosmolarity of spaces between epithelial cells and basolateral membrane infoldings