1. MOVEMENT OF MOLECULES ACROSS CELL MEMBRANES
物质的跨膜转运
MOVEMENT OF MOLECULES ACROSS CELL MEMBRANES
XIA Qiang（夏强）, MD & PhD
Department of Physiology
Room 518, Block C, Research Building
School of Medicine, Zijingang Campus
Tel: (Undergraduate School),
(Medical School)

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

3. Sizes, on a log scale

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

5. Organelles have their own membranes

6. Cell Membrane (plasma membrane) 细胞膜

7. Phospholipid bilayer

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

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

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

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

12. Lipid Bilayer Phospholipid Phosphatidylcholine Phosphatidylserine
Phosphatidylethanolamine
Phosphatidylinositol
Cholesterol
Sphingolipid

14. Lipid mobility Rotation reducing membrane fluidity
enhancing membrane fluidity

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

16. Integral proteins

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

18. Carbohydrates
Glycoprotein Glycolipid

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

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

21. 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)

22. 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).

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

24. Net flux accounts for solute movements in both directions.
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.

25. 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

26. Simple diffusion & gap junctions

27. 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

28. 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.

29. 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.

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

31. 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.

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

33. 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.

34. Characteristics of ion channels
Specificity
Gating

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

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

39. Na+ channel

40. Na+ channel
Balloonfish or fugu

41. Na+ channel conformation
Open-state
Closed-state
Closed Activated Inactivated

42. Ligand-gated Channel
e.g. N2-ACh receptor channel

43. Stretch-sensitive Channel
Closed Open
Stretch

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

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

46. 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.

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

48. Passage of water molecules through the aquaporin AQP1
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.

49. Model for water permeation through aquaporin

50. facilitated diffusion, solutes move in the direction predicted
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.

51. Active transport 主动转运 Primary active transport 原发性主动转运
Secondary active transport 继发性主动转运

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

53. The transported solute binds to the protein
as it is phosphorylated (ATP expense).

55. Extracelluar (mmol/L) Intracellular (mmol/L)
Concentration gradient of Na+ and K+
Extracelluar (mmol/L) Intracellular (mmol/L) Na K

56. 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.

57. Na+-K+ pump (Na+ pump, Na+-K+ ATPase)
electrogenic pump

58. 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

59. Other primary active transport
Primary active transport of calcium
Primary active transport of hydrogen ions
etc.

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

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

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

63. Cotransporters

64. Exchangers

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

68. Solvent + Solute = Solution
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.

69. 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.

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

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

73. Response to cell shrinking

74. Response to cell swelling

75. Endocytosis and Exocytosis 入胞与出胞

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

77. Endocytosis

78. Exocytosis

79. 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

80. Epithelial Transport

83. Glands

84. Summary Diffusion: solute moves down its concentration gradient:
simple diffusion:
small (e.g., oxygen, carbon dioxide)
lipid soluble (e.g., steroids)
facilitated diffusion:
requires transporter (e.g., glucose)

85. Active transport: solute moves against its concentration gradient:
primary active transport:
ATP directly consumed (e.g., Na+ -K+ ATPase)
secondary active transport:
energy of ion gradient (usually Na+) used to move second solute (e.g., nutrient absorption in gut)
Exo- and endo- cytosis:
large scale movements of molecules

86. Thank you for your attention!