1. Membrane Transport Xia Qiang, PhD Department of Physiology Zhejiang University School of Medicine Tel: 88206417, 88208252 Email: xiaqiang@zju.edu.cn

2. LEARNING OBJECTIVES Describe how solutes cross cell membranes Explain how charge, size, and solubility affect solute movement across cell membranes Contrast how transporters, pumps & channels work Describe how ion channels are gated Describe how epithelial transport works

3. Organelles have their own membranes

4. Cell Membrane (plasma membrane)

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. Importance of pumps, transporters & channels Basis of physiologic processes ▫Growth ▫Metabolic activities ▫Sensory perception Basis of disease ▫Defective transporters (cystic fibrosis) ▫Defective channels (long QT syndrome, paralysis) Basis of pharmacological therapies ▫Hypertension (diuretics) ▫Stomach ulcers (proton pump inhibitors)

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

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

9. 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.

10. 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

11. Simple diffusion & gap junctions

12. Facilitated Diffusion ▫Carrier-mediated

13. Characteristics of carrier-mediated diffusion net 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. 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.

16. Characteristics of ion channels ▫Specificity ▫Gating （门控）

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

20. Voltage-gated Channel –e.g. Voltage-dependent Na + channel

21. Na + channel Balloonfish or fugu

22. Closed Activated Inactivated Na + channel conformation –Open-state –Closed-state

23. Ligand-gated Channel –e.g. N 2 -ACh receptor channel

24. 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. membrane

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

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

27. 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.

28. Na-K Pump

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

31. 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 + -Ca 2+, Na + -H + exchange)

32. Cotransporters

33. Exchangers

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

37. 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. Solvent + Solute = Solution Osmosis （渗透）

38. Begin: The partition between the compartments is permeable to water and to the solute. After diffusional equilibrium has occurred: Movement of water and solutes has equalized solute and water concentrations on both sides of the partition.

39. Begin: The partition between the compartments is permeable to water only. After diffusional equilibrium has occurred: Movement of water only has equalized solute concentration.

41. Role of Na-K pump in maintaining cell volume

42. Response to cell shrinking

43. Response to cell swelling

44. Endocytosis and Exocytosis

45. Alternative functions of endocytosis: 1.Transcellular transport 2.Endosomal processing 3.Recycling the membrane 4.Destroying engulfed materials

46. Endocytosis

47. Exocytosis

48. Two pathways of exocytosis Constitutive exocytosis pathway -- Many soluble proteins are continually secreted from the cell by the constitutive secretory pathway Regulated exocytosis pathway -- Selected proteins in the trans Golgi network are diverted into secretory vesicles, where the proteins are concentrated and stored until an extracellular signal stimulates their secretion

49. Steps to exocytosis Vesicle trafficking: In this first step, the vesicle containing the waste product or chemical transmitter is transported through the cytoplasm towards the part of the cell from which it will be eliminated Vesicle tethering: As the vesicle approaches the cell membrane, it is secured and pulled towards the part of the cell from which it will be eliminated Vesicle docking: In this step, the vesicle comes in contact with the cell membrane, where it begins to chemical and physically merge with the proteins in the cell membrane Vesicle priming: In those cells where chemical transmitters are being released, this step involves the chemical preparations for the last step of exocytosis Vesicle fusion: In this last step, the proteins forming the walls of the vesicle merge with the cell membrane and breach, pushing the vesicle contents (waste products or chemical transmitters) out of the cell. This step is the primary mechanism for the increase in size of the cell's plasma membrane

50. Epithelial Transport （上皮转运）

51. Measurement of voltage in an epithelium

52. Models of epithelial solute transport

53. Mechanisms of intestinal glucose absorption

56. Models of “isotonic” water transport in a leaky epithelium

58. Glands

59. General concepts

60. Fatty acids enter the cells lining the small intestine by: A. Simple diffusion B. Facilitated diffusion C. Active transport

61. The PepT is a H+/peptide antiporter located in the small intestine. It has which of the following characteristics? A. requires ATP for activity B. exhibits maximal transport when saturated C. requires H+ and peptides for activity D. B and C E. A, B, and C