1. Membrane Transport Xia Qiang, PhD Department of Physiology
Room C518, Block C, Research Building, School of Medicine
Tel:

2. Sizes, on a log scale

3. Organelles have their own membranes

4. Cell Membrane (plasma membrane)

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

6. Phospholipid bilayer

7. 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

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

9. Composition of cell membrane:
Lipids
Proteins
Carbohydrates

10. Lipid Bilayer
Phospholipid Phosphatidylcholine Phosphatidylserine Phosphatidylethanolamine Phosphatidylinositol Cholesterol Sphingolipid

12. Lipid mobility Rotation reducing membrane fluidity
enhancing membrane fluidity

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

14. Integral proteins

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

16. Carbohydrates
Glycoprotein Glycolipid

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

18. 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）

19. 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).

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

21. 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.

22. 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

23. Facilitated Diffusion
Carrier-mediated

24. 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.

25. 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.

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

27. 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.

28. 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.

29. Characteristics of ion channels
Specificity
Gating（门控）

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

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

34. Na+ channel

35. Na+ channel
Balloonfish or fugu

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

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

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

39. 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

40. 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.

41. 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

42. 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.

43. Model for water permeation through aquaporin

44. 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.

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

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

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

48. 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.

49. Na-K Pump

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

53. 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

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

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

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

57. Countertransport（逆向转运）
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)

58. Cotransporters

59. Exchangers

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

63. 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.

64. 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.

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

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

68. Response to cell shrinking

69. Response to cell swelling

70. Endocytosis and Exocytosis

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

72. Endocytosis

73. Exocytosis

74. 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

75. 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

76. Epithelial Transport（上皮转运）

77. Measurement of voltage in an epithelium

78. Models of epithelial solute transport

79. Mechanisms of intestinal glucose absorption

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

84. Glands

85. THANK YOU!