Lecture 5: Solute Transport Across Cell Membranes Part 2

What is passive (uncoupled) transport?

moves down electrochemical gradient; doesn’t require energy

For ions and hydrophilic solutes, specialized pathways across membranes are needed such as what?

• pores

• channels

• carriers

Describe pores.

• always open

• straight tube structure

• no change in conformational state

What do porins allow?

allows solutes as large as 5 kDa to diffuse; water diffusion

Describe aquaporins.

• large family of proteins, expressed from bacteria to mammals

• specialized pores that form channels just large enough for water molecules to pass through

• form permeation pathways for single-file diffusion of water

What are the 4 major components of ion channels?

• gate: determines whether the channel is open or closed

• sensor(s): respond to changes in membrane voltage, 2nd messenger systems, or ligands

• selectivity filter: determines type(s) of ions that pass through (specificity)

• open channel pores

True or False: During each channel opening, multiple ions cross per open event, and ion flux can be detected as a small electrical current.

true

List the carrier-mediated transport process.

1. the carrier is open to the outside

2. X enters from outside and binds at a binding site

3. the outer gate closes and X becomes occluded, still attached to its binding site

4. the inner gate opens with X still bound

5. X exits and enters the inside of the cell

6. the inner gate closes, occluding an empty binding site; this cycle can also flow in reverse order

True or False: Carriers are conduits that are gated by two doors that are never open at the same time.

true

What is facilitated diffusion?

passive (downhill) movement of a solute by a carrier

True or False: Each carrier can transport a small, fixed number of solute particles per cycle.

true

What does the rate of carrier transport depend on?

• solute concentration

• number of carriers

True or False: There is a fixed number of carriers in the cell membrane, each with limited speed.

true

What is active (coupled) transport?

moves uphill against the electrochemical gradient

What is primary active transport?

energy needed comes from ATP hydrolysis

What is secondary active transport?

coupling uphill movement of one or more solutes to downhill movement of one or more other solutes

True or False: An example of secondary active transport is a favorable inward sodium electrochemical gradient (set up by primary transport) often used to drive secondary transport of another solute.

true

What needs to be considered with active transport?

• transported solute has to be bound when the pump is open to the side where concentration is low

• solute needs to be released on the side where concentration is high

• this process takes energy

What type of transporter are pumps?

primary active transporters

What are ATPases?

pumps energized by ATP hydrolysis

Describe the Na-K pump.

• nearly ubiquitous

• alpha subunit: catalytic subunit

• beta subunit: essential for pump assembly and membrane targeting

How does the Na-K pump work?

couples extrusion of 3 Na+ and uptake of 2 K+ to hydrolysis of 1 ATP

What is the Na-K pump responsible for maintaining?

low intracellular sodium and high intracellular potassium, relative to the extracellular fluid (ECF)

True or False: The Na-K pump is the only primary active transport process for sodium and the most important one for potassium.

true

What is the enzymatic cycle for the Na-K pump?

1. the E1 form of the pump, with ATP bound, is empty and exposed to the intracellular space

2. three 3 Na+ ions within the cell then bind to sites on E1

3. the ATP molecule is hydrolyzed, phosphorylating the alpha subunit; this phosphorylation of E1 results in a conformational change to E1-P, which occludes Na+ from both the cytosolic and extracellular space

4. the conformation of the pump spontaneously changes to E2-P, exposing the bound Na+ to the extracellular space, allowing it to exit the pump

5. the E2-P form of pump is empty and exposed to the extracellular space

6. 2 K+ ions outside the cell bind to sites on E2-P

7. with the loss of the phosphate, the conformation of the pump changes to E2, which occludes K+

8. an ATP molecule binds, causing a conformational change that returns the pump to its E1 state; K+ is exposed to the cytosolic space and leaves E1

True or False: The Na-K pump is electrogenic, and each cycle of the pump results in a net loss of a positive charge.

true

What does the rate of transport of the Na-K pump depend on?

• saturable function of intracellular Na+ and extracellular K+

• saturable function of intracellular ATP

• metabolic state

What are cotransporters?

secondary active transporters that move driving solute and riding solute in the same direction

What is an example of a cotransporter?

Na/glucose cotransporter

Where is the Na/glucsoe cotransporter located?

the apical membrane of cells that line the proximal tubule (kidney) and small intestine

What is the Na/glucose cotransporter stoichiometry?

Na/glucose is 1:1 or 2:1

What does the Na/K/Cl cotransporter do?

harnesses the energy of inward Na+ electrochemical gradient to drive the intracellular accumulation of Cl- and K+

What is the stoichiometry of the Na/K/Cl cotransporter?

Na:K:Cl ratio is 1:1:2

What does the K/Cl cotransporter do?

uses outwardly directed K+ gradient to drive the extrusion of Cl- from the cell

What is the stoichiometry of the K/Cl cotransporter?

K:Cl ratio is 1:1

What are exchangers?

secondary active transporters that move the driving solute and riding solute in opposite directions

True or False: In general, exchangers exchange cations for cations and anions for anions.

true

What is the Na-Ca exchanger highly expressed?

cardiac tissue

What is stoichiometry for the Na-Ca exchanger?

3 Na+ ions in per 1 Ca2+ ion out

What does the Na-Ca exchanger do?

helps maintain the inward electrochemical gradient for Ca2+

What is the stoichiometry for the Na-H exchanger?

1:1 exchange of 1 extracellular Na+ for 1 intracellular H+

Where is the Na-H exchanger present?

on the plasma membrane of almost every cell in the body

What does the Na-H exchanger do?

drives extrusion of H+ from the cell

How does Na+-driven Cl-HCO3 exchanger function?

couples movement of 1 Na+ and 2 HCO3- (in) to opposite movement of 1 Cl- (out)

True or False: The Cl-HCO3 exchanger functions independently of Na+.

true

What is the Cl-HCO3 exchanger expressed by?

virtually all cells in the body

What are Cl-HCO3 exchangers also known as?

anion exchangers (AEs)

What are Cl-HCO3 exchangers important for?

pH regulation

True or False: Cl-HCO3 exchangers are another important mechanism for intracellular Cl- accumulation.

true