Membrane Transport

1. Membrane Transport Xia Qiang, MD & PhD Department of Physiology Room C518, Block C, Research Building, School of Medicine Tel: 88208252 Email: xiaqiang@zju.edu.cn

2. Organelles have their own membranes

3. Cell Membrane (plasma membrane)

4. Membrane Transport Lipid Bilayer -- primary barrier, selectively permeable

5. Membrane Transport • Simple Diffusion（单纯扩散） • Facilitated Diffusion（易化扩散） • Active Transport（主动转运） • Endocytosis and Exocytosis（出胞与入胞）

6. START: Initially higher concentration of molecules randomly move toward lower concentration. Over time, solute molecules placed in a solvent will evenly distribute themselves. Diffusional equilibrium is the result (Part b).

7. At time B, some glucose has crossed into side 2 as some cross into side 1.

8. Note: the partition between the two compartments is a membrane that allows this solute to move through it. Net flux accounts for solute movements in both directions.

9. Simple Diffusion • Relative to the concentration gradient • movement is DOWN the concentration gradient ONLY (higher concentration to lower concentration) • Rate of diffusion depends on • The concentration gradient • Charge on the molecule • Size • Lipid solubility

10. Facilitated Diffusion • Carrier-mediated

11. A cartoon model of carrier-mediated transport. The solute acts as a ligand that binds to the transporter protein…. … and then a subsequent shape change in the protein releases the solute on the other side of the membrane.

12. In simple diffusion, flux rate is limited only by the concentration gradient. In carrier- mediated transport, the number of available carriers places an upper limit on the flux rate.

13. Characteristics of carrier-mediated diffusionnet movement always depends on the concentration gradient • Specificity • Saturation • Competition

14. Channel-mediated 3 cartoon models of integral membrane proteins that function as ion channels; the regulated opening and closing of these channels is the basis of how neurons function.

15. A thin shell of positive (outside) and negative (inside) charge provides the electrical gradient that drives ion movement across the membranes of excitable cells.

16. The opening and closing of ion channels results from conformational changes in integral proteins. Discovering the factors that cause these changes is key to understanding excitable cells.

17. Characteristics of ion channels • Specificity • Gating（门控）

18. Three types of passive, non-coupled transport through integral membrane proteins

21. I II III IV Outside + + + + + + + + + + + + Inside NH2 CO2H Voltage-gated Channel • e.g. Voltage-dependent Na+ channel

22. Na+ channel

23. Na+ channel Balloonfish or fugu

24. Closed Activated Inactivated Na+ channel conformation • Open-state • Closed-state

25. Ligand-gated Channel • e.g. N2-ACh receptor channel

26. Aquaporin • Aquaporins are water channels that exclude ions • Aquaporins are found in essentially all organisms, and have major biological and medical importance

27. The Nobel Prize in Chemistry 2003 "for discoveries concerning channels in cell membranes" "for structural and mechanistic studies of ion channels" "for the discovery of water channels" Peter Agre Roderick MacKinnon

28. The dividing wall between the cell and the outside world – including other cells – is far from being an impervious shell. On the contrary, it is perforated by various channels. Many of these are specially adapted to one specific ion or molecule and do not permit any other type to pass. Here to the left we see a water channel and to the right an ion channel.

29. Peter Agre’s experiment with cells containing or lacking aquaporin. The aquaporin is necessary for making the cell absorb water and swell

30. Passage of water molecules through the aquaporin AQP1. Because of the positive charge at the center of the channel, positively charged ions such as H3O+, are deflected. This prevents proton leakage through the channel.

31. Model for water permeation through aquaporin

32. membrane In both simple and facilitated diffusion, solutes move in the direction predicted by the concentration gradient. In active transport, solutes move opposite to the direction predicted by the concentration gradient.

33. Active transport • Primary active transport（原发性主动转运） • Secondary active transport（继发性主动转运）

34. Primary Active Transport making direct use of energy derived from ATP to transport the ions across the cell membrane

35. Concentration gradient of Na+ and K+ Extracelluar (mmol/L) Intracellular (mmol/L) Na+ 140.0 15.0 K+ 4.0 150.0

36. Here, in the operation of the Na+-K+-ATPase, also known as the “sodium pump,” each ATP hydrolysis moves three sodium ions out of, and two potassium ions into, the cell.

37. Na-K Pump

38. Na+-K+ pump (Na+ pump, Na+-K+ ATPase) electrogenic pump（生电性泵）

40. Physiological role of Na+-K+ pump • Maintaining the Na+ and K+ gradients across the cell membrane • Partly responsible for establishing a negative electrical potential inside the cell • Controlling cell volume • Providing energy for secondary active transport

41. Other primary active transport • Primary active transport of calcium • Primary active transport of hydrogen ions • ……

42. Secondary Active Transport • The ion gradients established by primary active transport permits the transport of other substances against their concentration gradients

43. Secondary active transport uses the energy in an ion gradient to move a second solute.

44. Cotransport（同向转运） the ion and the second solute cross the membrane in the same direction (e.g. Na+-glucose, Na+-amino acid cotransport) Countertransport（逆向转运） the ion and the second solute move in opposite directions (e.g. Na+-Ca2+, Na+-H+ exchange)

45. Cotransporters

46. Exchangers

47. Ion gradients, channels, and transporters in a typical cell

50. Osmosis（渗透） Solvent + Solute = Solution Here, water is the solvent. The addition of solute lowers the water concentration. Addition of more solute would increase the solute concentration and further reduce the water concentration.