CB Lecture 4 membrane transport

What is the main idea of membrane transport?

The cell membrane is a barrier that controls what enters and leaves the cell. Small nonpolar molecules can cross by simple diffusion, but ions and most polar molecules require transport proteins such as channels and transporters. Molecules can move passively down their electrochemical gradient or actively against their gradient using energy from ATP, ion gradients, or light.

What determines whether a molecule can cross a lipid bilayer by simple diffusion?

Small size, hydrophobic/nonpolar character, and lack of charge make molecules more able to cross by simple diffusion. Ions and most large or uncharged polar molecules require transport proteins.

What are the two major classes of membrane transport proteins?

Channels and transporters (also called carriers).

What are three important properties of membrane transport proteins?

• Specificity: Transport proteins move only specific molecules or very similar molecules.

• Saturation: Transport reaches a maximum rate when all transport proteins are occupied.

• Competition: Similar molecules compete for the same transport protein, slowing transport.

What is passive transport?

Movement of a molecule down its concentration or electrochemical gradient without an external energy input.

What is active transport?

Movement of a molecule against its concentration or electrochemical gradient using an energy source.

What are the three energy sources for active transport?

ATP hydrolysis, an electrochemical gradient, and light.

What is the difference between a channel and a transporter?

A channel forms a hydrophilic pore through which molecules move, while a transporter binds its cargo and changes conformation to move it across the membrane.

What are important properties of ion channels?

They are selective, form pores, do not bind ions during transport, transport ions very rapidly, only allow passive transport, and can be gated by voltage, ligands, or mechanical force.

What does it mean that an ion channel is selective?

The channel allows certain ions to pass based on properties such as charge and size while excluding others.

Why are channels faster than transporters?

Ions move through an open pore rather than requiring binding and repeated conformational changes for every molecule transported.

Can an ion channel move an ion against its electrochemical gradient?

No. Channels only allow passive movement down the ion's electrochemical gradient.

What are the three major types of gated ion channels?

Voltage-gated: response to changes in the electrical charge

ligand-gated:specific chemical molecule binds to the channel protein.

mechanically gated channels: response to physical deformation or mechanical stress such as touch, pressure, or vibration.

What is a chemical gradient?

A difference in the concentration of a molecule across a membrane.

What is an electrical gradient?

A force on a charged molecule caused by a difference in electrical charge across a membrane.

What two conditions are required for an electrical gradient?

The molecule must be charged, and there must be a charge difference across the membrane or a membrane potential that is not zero.

What is an electrochemical gradient?

The combined effects of the chemical gradient and electrical gradient acting on an ion.

What determines the direction an ion will move?

The overall electrochemical gradient, meaning both the concentration difference and electrical forces must be considered.

How can you remember an electrochemical gradient?

It is the chemical push caused by concentration plus the electrical pull caused by charge.

Why is a potassium channel selective for K+ instead of Na+?

Carbonyl groups in the selectivity filter are spaced perfectly to stabilize a dehydrated K+. Na+ is too small to interact optimally with these groups, making passage energetically unfavorable.

Why doesn't the smaller Na+ ion fit through a K+ channel?

Selectivity is not simply about physical size. Na+ is too small to make the correct interactions with the carbonyl groups that replace K+'s hydration shell.

What is the main idea behind K+ channel selectivity?

K+ is the correct size to interact with the selectivity filter, while Na+ is too small to be properly stabilized.

What happens when an action potential reaches a nerve terminal?

Voltage-gated Ca2+ channels open, allowing Ca2+ to enter the nerve terminal.

How does Ca2+ entry into a nerve terminal transmit a signal across a synapse?

Ca2+ triggers neurotransmitter-containing vesicles to release neurotransmitter into the synaptic gap.

What happens after neurotransmitter is released into the synapse?

The neurotransmitter binds receptors on the postsynaptic cell and opens ion channels.

What triggers an action potential in the postsynaptic cell?

Neurotransmitter-gated channels open and allow Na+ to enter the postsynaptic cell, propagating the signal.

What is facilitated or transporter-mediated diffusion?

Passive transport in which a molecule binds to a transporter and moves down its gradient without an energy input.

Why can transporter-mediated diffusion become saturated?

There are a limited number of transporters, so at high solute concentrations all transporters can become occupied and the transport rate reaches a maximum.

How does the graph of simple diffusion differ from transporter-mediated diffusion?

Simple diffusion shows a linear increase in transport rate as concentration increases, while transporter-mediated diffusion eventually plateaus because the transporters become saturated.

How can you identify simple diffusion on a transport kinetics graph?

The transport rate increases proportionally and linearly as solute concentration increases.

How can you identify transporter-mediated diffusion on a transport kinetics graph?

The transport rate increases at first but eventually reaches a plateau at high solute concentrations because the transporters become saturated.

What is an easy analogy for why transporter-mediated diffusion plateaus?

Transporters are like a limited number of checkout lanes. Once every transporter is occupied, adding more molecules cannot increase the transport rate.

Why does simple diffusion not reach the same saturation plateau as transporter-mediated diffusion?

Simple diffusion does not depend on a limited number of transport proteins that can become fully occupied.

Why do cells use active transport?

To concentrate needed metabolites, remove harmful or inhibitory ions, and maintain proper ion balance such as H+, K+, Na+, Ca2+, and Cl−.

What is the approximate Na+ concentration inside vs. outside an animal cell?

Inside: approximately 5–15 mM. Outside: approximately 145 mM.

What is the approximate K+ concentration inside vs. outside an animal cell?

Inside: approximately 140 mM. Outside: approximately 5 mM.

What is the approximate Ca2+ concentration inside vs. outside an animal cell?

Inside: approximately 10^-4 mM. Outside: approximately 1–2 mM.

Which ion is high outside and low inside the cell?

Na+.

Which ion is high inside and low outside the cell?

K+.

What is special about the Ca2+ concentration gradient?

Free Ca2+ concentration is extremely low inside the cell and much higher outside the cell.

How does ATP hydrolysis drive active transport?

ATP hydrolysis can phosphorylate a pump, and the energy stored in that phosphorylation drives conformational changes that move molecules against their gradient.

What is the Na+/K+ pump?

An ATP-driven pump that transports Na+ out of the cell and K+ into the cell against their concentration gradients.

What is the stoichiometry of the Na+/K+ pump?

For every pumping cycle, 3 Na+ are pumped out and 2 K+ are pumped in.

Which ions are transported against their concentration gradients by the Na+/K+ pump?

Both Na+ and K+.

What is the energy source for the Na+/K+ pump?

ATP hydrolysis.

What are the steps of the Na+/K+ pump cycle?

3 Na+ bind inside, ATP phosphorylates the pump, the pump changes shape and releases Na+ outside, 2 K+ bind outside, the pump is dephosphorylated, the pump returns to its original shape, and K+ is released inside.

What causes the Na+/K+ pump to release Na+ outside the cell?

Phosphorylation of the pump causes a conformational change that exposes the Na+-binding sites to the extracellular side.

What causes the Na+/K+ pump to release K+ inside the cell?

K+ binding promotes dephosphorylation, allowing the pump to return to its original conformation and release K+ into the cytosol.

What is the easiest way to memorize the Na+/K+ pump?

3 Na+ out, ATP phosphorylates the pump, then 2 K+ in.

What would happen if ATP were replaced with ATP-γ-S, a non-hydrolyzable ATP analog?

The pump could not complete its normal ATP-dependent phosphorylation cycle, so continued Na+/K+ transport would stop.

Why is the Na+/K+ pump important?

It establishes Na+ and K+ gradients, contributes to membrane potential, keeps cytosolic Na+ low, and creates stored energy that can drive other transport processes.

How much energy can a typical animal cell devote to the Na+/K+ pump?

About one-third, or 30% or more, of total cellular ATP consumption.

What is coupled transport?

Using the energy stored in one molecule or ion moving down its electrochemical gradient to drive another molecule against its gradient.

How does the Na+/K+ pump indirectly help transport glucose?

It uses ATP to keep intracellular Na+ low, creating a Na+ electrochemical gradient that can then provide energy for Na+-coupled glucose transport.

What is the Na+/glucose symporter?

A transporter that uses Na+ moving down its electrochemical gradient to drive glucose into the cell against its concentration gradient.

Is the Na+/glucose symporter primary or secondary active transport?

Secondary active transport because it directly uses the energy stored in the Na+ electrochemical gradient rather than directly using ATP.

Why can Na+ movement drive glucose uptake through the symporter?

Na+ has a strong tendency to move into the cell down its electrochemical gradient, and the symporter couples that energetically favorable movement to glucose uptake against its gradient.

What is the energy chain for Na+-dependent glucose transport?

ATP powers the Na+/K+ pump, the pump creates the Na+ gradient, and the Na+ gradient powers the Na+/glucose symporter to bring glucose into the cell.

Where is the Na+/glucose symporter located in an intestinal epithelial cell?

The apical membrane, facing the intestinal lumen.

What happens when Na+ and glucose bind the Na+/glucose symporter?

The transporter undergoes a conformational change and carries both Na+ and glucose together into the epithelial cell.

Why is Na+/glucose symport effectively directional in intestinal cells?

Na+ is abundant outside the cell but kept very low inside, so Na+ and glucose are much more likely to bind together on the intestinal lumen side than on the cytosolic side.

What is a glucose uniporter?

A passive transporter that allows glucose to move down its concentration gradient.

Where is the glucose uniporter located in the intestinal epithelial cell example?

The basolateral membrane, facing the extracellular fluid.

What does the basolateral glucose uniporter do?

It allows glucose to leave the epithelial cell and enter the extracellular fluid down its concentration gradient.

Where is the Na+/K+ pump located in an intestinal epithelial cell?

The basolateral membrane.

Why are all three transporters needed for intestinal glucose absorption?

The Na+/K+ pump creates the Na+ gradient, the Na+/glucose symporter uses that gradient to bring glucose into the cell from the intestinal lumen, and the glucose uniporter allows glucose to leave the cell into extracellular fluid.

What is the overall path of glucose during intestinal absorption?

Intestinal lumen, then epithelial cell through the Na+/glucose symporter, then extracellular fluid through the glucose uniporter, and eventually into the bloodstream.

What is the overall role of the Na+/K+ pump in intestinal glucose absorption?

It pumps Na+ out of the epithelial cell to maintain low intracellular Na+, preserving the Na+ gradient required for the Na+/glucose symporter to function.

How can you remember the roles of the three intestinal transporters?

Pump creates the Na+ gradient, symporter uses the gradient to bring in glucose, and uniporter lets glucose leave.

What are tight junctions?

Structures formed between adjacent epithelial cells that seal the cells and separate the apical and basolateral membrane domains.

Why are tight junctions important for directional glucose transport?

They prevent transport proteins from diffusing between the apical and basolateral membranes and prevent direct movement of material between the two sides of the epithelial cell layer.

How can tight junctions be thought of simply?

They act like a fence that keeps apical transporters on one side and basolateral transporters on the other side.

What would happen if epithelial transporters were randomly distributed around the cell membrane?

Directional transport from the intestinal lumen to the extracellular fluid would be disrupted because the coordinated transport pathway would no longer be properly organized.

What would happen if the Na+/glucose symporter were moved from the apical membrane to the basolateral membrane?

Normal uptake of glucose from the intestinal lumen would be disrupted because the symporter would no longer be positioned on the side facing the intestinal lumen.

What would happen if the passive glucose transporter were moved from the basolateral membrane to the apical membrane?

Glucose could move in the wrong direction, disrupting the normal transfer of absorbed glucose from the epithelial cell into the extracellular fluid.

How does depletion of an energy source affect active transport?

Transport that depends directly or indirectly on that energy source will decrease or stop because the transporter can no longer drive molecules against their gradient.

How does a steeper favorable gradient affect passive transport?

A steeper gradient provides a stronger driving force for passive movement down the gradient.

What happens to passive transport if the gradient becomes shallower?

The driving force decreases, so net passive transport decreases.

What happens if the direction of a concentration or electrochemical gradient reverses?

The direction of passive transport can reverse, causing net movement in the opposite direction.

How does depletion of ATP affect the Na+/K+ pump?

The pump cannot continue its ATP-dependent cycle, so Na+ and K+ gradients will eventually dissipate.

How would loss of the Na+ gradient affect the Na+/glucose symporter?

Glucose uptake would decrease or stop because the symporter depends on the energy stored in the Na+ electrochemical gradient.

What is the relationship between primary and secondary active transport in intestinal glucose uptake?

Primary active transport uses ATP directly through the Na+/K+ pump to create the Na+ gradient, while secondary active transport uses that Na+ gradient through the Na+/glucose symporter to concentrate glucose