Human Physiology

1. Human Physiology 人体生理学 Qiang XIA (夏强), MD & PhD Department of Physiology Room C518, Block C, Research Building, School of Medicine Tel: 88208252 Email: xiaqiang@zju.edu.cn

2. Course Structure • Lectures: 80 academic hours • 5 a.h./week • 2 a.h. on Tue., 3 a.h. on Fri. • Practicals: 64 a.h. • 4 a.h./week

3. Evaluation Participation in practicals: 5% Practical reports: 15% Weekly assessments & midterm exam: 30% Final examination: 50%

4. Recommended textbook Widmaier EP, Raff H, Strang KT (2006) Vander’s Human Physiology: The Mechanisms of Body Function, Tenth Edition. McGraw-Hill.

5. Course website • Medical School Course Center: • http://10.71.121.158 • Course website: • http://10.71.121.158/G2S/Template/View.aspx?action=view&courseType=0&courseId=27123

6. MOVEMENT OF MOLECULES ACROSS CELL MEMBRANES 物质的跨膜转运

7. Outline Cell structure Simple diffusion Facilitated diffusion Active transport Endocytosis and exocytosis

8. Sizes, on a log scale

9. Ostrich egg

10. Electron Micrograph of organelles in a hepatocyte (liver cell)

11. Organelles have their own membranes

12. Cell Membrane (plasma membrane)细胞膜

13. Electron micrograph and sketch of plasma membrane surrounding a human red blood cell

14. Phospholipid bilayer

15. The amino acids along the membrane section are likely to have non-polar side chains Circles represent amino acids in the linear sequence of the protein Schematic cartoon of a transmembrane protein

16. Structure of cell membrane: Fluid Mosaic Model (Singer & Nicholson, 1972)

17. Drawing of the fluid-mosaic model of membranes, showing the phospholipid bilayer and imbedded proteins

18. Composition of cell membrane: • Lipids 脂类 • Proteins 蛋白质 • Carbohydrates 糖类

19. Lipid Bilayer Phospholipid Phosphatidylcholine Phosphatidylserine Phosphatidylethanolamine Phosphatidylinositol Cholesterol Sphingolipid

21. Rotation Lipid mobility reducing membrane fluidity enhancing membrane fluidity

22. Membrane proteins Integral (intrinsic) proteins Peripheral (extrinsic) proteins Integral protein Peripheral protein

23. Integral proteins

24. Adhesion Some glycoproteins attach to the cytoskeleton and extracellular matrix. Functions of membrane proteins

25. Carbohydrates Glycoprotein Glycolipid

26. Membrane Transport 跨膜转运 Lipid Bilayer -- primary barrier, selectively permeable

27. Membrane Transport • Simple Diffusion • Facilitated Diffusion • Active Transport • Endocytosis and Exocytosis Primary Active Transport Secondary Active Transport

28. 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).

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

30. 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.

31. Simple Diffusion 单纯扩散 • 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 • Temperature

32. Facilitated Diffusion 易化扩散 • Carrier-mediated diffusion 载体中介的扩散 • Channel-mediated diffusion 通道中介的扩散

33. A cartoon model of carrier-mediated diffusion 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.

34. 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.

35. Characteristics of carrier-mediated diffusion: net movement always depends on the concentration gradient • Specificity • Saturation • Competition

36. Channel-mediated diffusion 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.

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

38. 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.

39. Characteristics of ion channels • Specificity • Gating

40. Channel Types: • Voltage-gated Channel • Ligand-gated Channel • Stretch-sensitive Channel • Others

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

42. Na+ channel

43. Na+ channel Balloonfish or fugu

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

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

46. Stretch Closed Open Stretch-sensitive Channel

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

48. 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 http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/public.html

49. 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.

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