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

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

2. 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.

3. Membrane Transport: Carriers & Channels

4. 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

5. 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

6. Membrane protein transporter types Channels facilitate diffusion through an aqueous pore when a conformational change opens a gate Some carrier types facilitate diffusion, others use energy to pump molecules against Their gradient. They must bind the solute to initiate a conformational change

7. 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

8. 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

9. How carrier proteins change conformation The ligand binding site is exposed on the upper membrane surface

10. The folding pattern flips to a different position The ligand binding site is now exposed on the lower membrane surface

11. Without the ligand bound, conformation returns to the first state The carrier is now ready to transport another molecule

12. 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

13. Band 3 facilitated diffusion anion antiporter in red blood cells • When the bicarbonate diffusion gradient is reversed, the process reverses

14. Band 3 function in RBCs Why HCO3- for CO2? Why antiport Cl-?

15. 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

16. The Na+ - K+ pump cycle

17. The Na+- K+ ATPase pump is responsible for maintaining cellular osmotic balance Charged intracellular molecules attract ions & increase internal tonicity The pump’s net effect is to remove + ions

18. If the pump is blocked by ouabain More water enters

19. 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

20. Retrieval of GI tract glucose by enterocytes

21. 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

22. IK+ channel blocks Na+

23. IIK+ channel blocks Na+

24. 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

25. 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

26. Ligand gated channels • Binding of ligand changes conformation of the channel • Gate opens to allow an ion (+ or -) to enter or exit the cell

27. 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

28. 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

29. 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?

30. 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

31. Mechanically gated channels: hair cells in the ear

32. Sherman says Actually, I like to eat them proteins