stephen fish, ph.d. marshall university j. c. e. school of medicine fish@marshall.edu

Stephen Fish, Ph.D.Marshall University J. C. E. School of MedicineFish@Marshall.edu

Note to instructors:

I use these PowerPoint slides in cell biology lectures that I give to first year medical students. Copy the slides, or just the illustrations into your own teaching media. We all know that teaching science often requires compromises and simplification for specific student populations, or the requirements of a specific course. Please feel free to offer suggestions for improvements, corrections, or additional illustrations. I would be pleased to hear from anyone who finds my work useful, and am always willing to make it better. Also, the images have been compressed to screen resolution to keep PowerPoint file size down, and I can provide them at any resolution.

Stephen E. Fish, Ph.D.

Membrane Transport: Carriers & Channels

The membrane lipid barrier:Passive diffusion through the lipid bilayer

• Concentration gradient up, diffusion up• Molecule lipid solubility up, diffusion up• Molecular size up, diffusion down• Molecule electrically charged, diffusion blocked

Specialized membrane proteins transport molecules across membranes

• Simple diffusion– Species of molecule limited

by membrane physics– Rate is slow and linearly

related to concentration gradient

• Membrane transport– Overall not limited by size,

charge, or hydrophilia– Is highly selective for

specific needed molecules– Rate is fast and not linear

Some carrier types facilitatediffusion, others use energyto pump molecules againstTheir gradient. They mustbind the solute to initiatea conformational change

Membrane protein transporter types

Channels facilitate diffusionthrough an aqueous porewhen a conformationalchange opens a gate

Carrier types

• Uniporter- transports only one molecule species• Symporter- coupled transport of 2 different molecular

species in the same direction• Antiporter- coupled transport of 2 different molecular

species in the opposite direction• Symporters & antiporters are usually pumps• Some types transport more than one molecule of a

species/cycle

The glucose uniporter transports glucose across membranes

• Ligand (glucose) binding flips the transporter to a different conformation (changes shape)

• The new conformation releases glucose on the other side of the membrane

• Release allows it to flip back to repeat the cycle

How carrier proteins change conformation

The ligand bindingsite is exposed onthe upper membranesurface

The folding pattern flips to a different position

The ligand bindingsite is now exposed onthe lower membranesurface

The carrier isnow ready totransport anothermolecule

Without the ligand bound, conformation returns to the first state

Band 3 facilitated diffusion anion antiporter in red blood cells

• Multipass protein that binds to spectrin

• Exchanges Cl- for HCO3-

• Important for transporting CO2 to the lungs

Band 3 facilitated diffusion anion antiporter in red blood cells

• When the bicarbonate diffusion gradient is reversed, the process reverses

Band 3 function in RBCs

Why HCO3- for CO2?

Why antiport Cl-?

Primary active transport example:The Na+- K+ antiporter pump

• Pumps 3 Na+ ions out of cell & 2 K+ ions in• Maintains Na+ & K+ cell membrane gradients• Each cycle uses one ATP, 100 cycles/sec• Uses ¼ energy of most cells, ¾ for neurons

The Na+ - K+ pump cycle

The Na+- K+ ATPase pump is responsible for maintaining cellular osmotic balance

Charged intracellularmolecules attract ions& increase internal tonicity

The pump’s neteffect is toremove + ions

If the pump is blocked by ouabain

More waterenters

Secondary active transport example: The sodium-glucose symporter pump

• Gradients from primary pumps power secondary active transport

• Different types, can be antiporters or symporters• Pictured, the Na+ gradient powers conformational

change• Glucose is pumped in against its gradient

Retrieval of GI tract glucose by enterocytes

Channels are selective for ion species

• Some are very specific, others less

• Specificity based on– Size– Charge

• Special problem for K+ channels– Na+ is smaller & same

charge– Requires a special filter

IK+ channel blocks Na+

IIK+ channel blocks Na+

Most channel transporters are gated

• Opening & closing of the gate mechanism– Ligand gated– Voltage gated– Mechanically gated– Other types later in the

course

• A few are not gated = leak channels

Leak channels

• Open all the time• Best known type are K+

channels• K+ going down

concentration gradient out of the cell

• Increases inside negativity of the cell

• Gradient created by the Na+-K+ pump

Ligand gated channels

• Binding of ligand changes conformation of the channel

• Gate opens to allow an ion (+ or -) to enter or exit the cell

The K+ leak channel charges up the membrane

• The K+- Na+ pump charges up concentration gradients

• Excess + ions out accounts for only a small portion of the -60mv membrane potential

• The leak channel lets more + ions out

• The electrical potential rises until it equals & balances the K+ concentration gradient = no more leak

Hormones can trigger secretion

• Example- Pancreatic cells secrete digestive enzymes into the small intestine

• The cell is charged up by the leak channel

• Ligand opens gate on Ca++ channel

• Membrane potential & Ca++ gradient sum

• Ca++ entering triggers fusion of vesicles with membrane

Voltage gated channels

• Are sensitive to voltage across the cell membrane

• When the voltage changes to a trigger level, it opens

• The gate will close again when the voltage returns to the trigger level

• What is the problem with this picture?

Many channels are inactivated by a separate mechanism than the gate

• The voltage gated Na+ channel serves as a good example

• Opening the channel depolarizes the cell & if it stayed open the gate would never close

• The inactivating mechanism provides for a short positive pulse of current into the cell

Mechanically gated channels: hair cells in the ear

Sherman says

Actually, I like to eat them proteins