The document discusses various mechanisms of transport across cell membranes, including passive transport through diffusion and facilitated diffusion, as well as active transport. Passive transport involves the spontaneous movement of substances down their concentration gradients, while active transport requires energy and transports substances against their gradients using protein pumps or channels. Specific examples discussed include sodium-potassium pumps, aquaporin channels for water transport, and glucose transporters.

1. TRANSPORT ACROSS THE
CELL MEMBRANE
1
DR.HAMISI MKINDI,MD.
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2. The cell membrane provides a barrier
that separate ECF and ICF compartments.
• For survival the body must maintain the volume
and composition of both ECF and ICF.
• This due in part transport across cell membrane.
2

3. These include passive
and active mechanism
3

4. 4
Passive
transport
Simple
Diffusion
Facillated
Diffusion
Active
transport
Primary
Active
Transport
Secondary
Active
Transport

5. Diffusion through the cell membrane
is divided into two subtypes:
•Simple diffusion and
•Facilitated diffusion
5

6. In simple diffusion movement
occurs without carrier
proteins in cell membrane.
6

7. Simple diffusion can occur through
the cell membrane by two pathways:
•Through the lipid bilayer if lipid soluble and
•Through watery channels if water soluble.
7

8. Lipid bilayer is intrinsically impermeable
to ions and polar molecules.
• Permeability is conferred by membrane proteins,
• Pumps or Channels
8

9. 9
TRANSPORT
PROTEINS
INCLUDE
PUMPS
For active
transport
CARRIERS
For facilitated diffusion
ION CHANNELS

10. Pumps use a source of
free energy to drive
uphill ions or molecules.
10

11. These allow movement from
an area of low to an area
with a higher concentration.
11

12. Protein Channels provide
passageway for water
and small, polar ions.
12

13. Protein channel may exist in a state
which stays open all the time.
•These are called non-gated channel protein.
•Gated channel protein remains closed,
•Until it receives an electrical or chemical signal
13

14. 14
Non-gated channels Gated Channels

15. Many of the body’s cell membranes
contain protein “pores” called
•Aquaporins (water channels)
15

16. 16
AQP are usually specific for water
permeability
 Water molecules traverse in single file.
All aquaporins are impermeable to
charged solutes.

17. Diffusion of water occuring through
protein channels is so rapid
•Amount of water that diffuses in each direction
through the RBC membrane in a second is
•About 100 times the volume of the RBC itself.
17

18. Other lipid-insoluble molecules
can pass through protein channels
•In the same way as water molecules
• If water soluble and small enough.
18

19. Protein channels distinguished by
two important characteristics:
•They are often selectively permeable
•Respond to electrical or chemical stimuli.
19

20. Ion channels may therefore be
classified in a number of ways
•Nature of their gating,
•The species of ions passing
20

21. Gating is one of the characteristics
of ion channels and pores
•An external signal determines if:
•The channel is open or if it is closed
21

22. Channels can be opened or closed
by GATES regulated by
•Electrical signals (voltage-gated channels) or
•Chemicals that bind to the channel proteins
(ligand-gated channels).
22

23. Examples of voltage gated channels
include the Na+ and K+ channels
•Found in nerves and muscle; important in:
•Neurotransmitter release at nerve endings.
23

24. 24
Na+ Channel Ca++ Channel K+ Channel Cl- Channel
VOLTAGE GATED CHANNELS

25. 25
SODIUM CHANNELS

26. 26
INACTIVATED
OPEN

27. The voltage gated sodium
channel actually has two gates
•One near the outside the activation gate,
•The other inside called inactivation gate.
27

28. 28
Diagrammatic
representation of the two
sodium channel gates

29. 29

30. When the membrane potential
becomes less negative it causes
•A conformational change in activation gate,
•Flipping it all the way to open position.
30

31. This is called activated state;
•During this state, sodium ions can
pour inward through the channel,
31

32. 32
OPEN

33. The same increase in voltage that
opens the activation gate also
•Closes the inactivation gate.
•After a brief period (few 10,000th of a sec)
33

34. The sodium channel therefore
remains open briefly
•When the inactivation gate closes,
•Sodium ions no longer enter the cell.
34

35. 35
INACTIVATED

36. 36
POTASSIUM CHANNELS

37. During the resting state the gate of
the potassium channel is closed
•When membrane potential rises gate opens
•Allowing K+ to diffuse outward.
37

38. 38

39. The K+ gates open just
as the Na+ channels
begin to close.
39

40. 40

41. This provides a mechanism
for generating an action
potential
41

42. An action potential is a
sudden transitory change
in the resting potential.
42

43. Depolarization occurs at a
time, the membrane suddenly
becomes permeable to
sodium ions
Repolarization occurs at a
time when the sodium
cannels close and the
potassium channels open
43

44. 44

45. Only neurons and muscle cells
are capable of generating
an action potential
45

46. In neurons play a central role
in cell-to-cell communication
• Propagating signals along a neuron
46

47. The primary role of voltage-gated Na+
channels is to produce the initial
•Depolarizing phase of fast action potentials
•In neurons and skeletal and cardiac muscle
•Na+ channels are blocked by local anesthetics
47

48. Natural mutations in the human
gene for this Na+ channel result in a
•Variety of human genetic diseases, such as
•Hyperkalemic periodic paralysis, and
•Several types of myotonia
48

49. Ligand-gated channels open
in response to the binding of a
chemical messenger (ligand)
49

50. LIGAND GATED CHANNELS
50

51. Ions passing through ligand-
gated- channels include
•Na+, K+, Ca++, or Cl-
51

52. 52
CALCIUM CHANNELS

53. 53

54. Many of the protein channels
are highly selective
•Transport one or more specific ions
or molecules.
54

55. Selectivity depend on characteristics
of the channel itself, such as its
•Diameter, shape, electrical charges and
•Chemical bonds along its inside surfaces.
55

56. One of the most important of the
protein channels is the sodium channel
•The inner surfaces are strongly negatively charged
•The charges pull dehydrated Na+ into the channel.
56

57. 57

58. Potassium channels permit
passage of K+ across the cell
membrane about 1000 times
more readily than they
permit Na+
58

59. The potassium channel has
a narrow selectivity filter.
•Lined by carbonyl oxygens.
59

60. When K+ enter the selectivity filter
they interact with carbonyl oxygens
•Shed most of their bound water molecules,
•Permitting dehydrated K+ to pass through
60

61. The sodium ion is smaller than
the potassium ion but has
• Difficulty going thru the K+ channel
61

62. The carbonyl oxygens are too
far apart to interact closely
with the smaller sodium ion
62

63. Therefore effectively excluded
by the selectivity filter from
passing through the pore.
63

64. Calcium channels display
selective permeability to
calcium ions.
64

65. Calcium plays an important role in
• Muscle contraction
• Transmitting messages through nerves
• The release of hormones
65

66. There are essentially
two classes of
calcium channels
L-Type Calcium
Channels
T-Type Calcium
Channels
66

67. The L-type calcium channel are part of the high-
voltage activated family of voltage-dependent
calcium channels
• "L" stands for long-lasting referring to the length of activation.
• Are expressed in skeletal, smooth, & cardiac muscle as well as
• Neurons and Endocrine Cells
67

68. L-type calcium channels are responsible
amongst others for
•Excitation-contraction coupling in muscle
•Aldosterone secretion in the adrenal cortex,
•They are inhibited by Calcium Channel Blockers.
68

69. 69
Calcium Channel Blockers
Calcium channel
blockers lower BP
prevent Ca++ entering
cells of blood vessels

70. T-Type calcium channels are low
voltage activated calcium channels
•These channels aid in mediating calcium influx
•Amongst other functions; control the pace-
making activity of the SAN
70

71. Facilitated diffusion is also called
carrier-mediated diffusion
•Requires interaction with a carrier protein by
•Binding chemically with them and
•Shuttling them through the membrane.
71

72. Among the most
important substances that
cross cell membranes by
facilitated diffusion are
glucose and most of the
amino acids.
72

73. There are at least two families of
glucose transporters
• Sodium Dependent Transporters SGLT-1-3
• Facilitative Glucose Transporters (GLUT1-14)
73

74. SGLT have binding sites
for both Na+ and GLU
74

75. 75

76. Found in epithelial cells kidney
and intestine
•Involved in secondary active transport
•During trans-epithelial transport
76

77. 77
Driving force is
generated by
Na+-K+ pump

78. Glucose Transporters (GLUT) are a
family of closely related proteins
•These are integral proteins
•Differ have no homology with SGLT-1-3

79. GLUT1(bbb),GLUT3(Pink Placenta,Neuron/brain,kidneys)
used basal GLU uptake in a number of
tissues:
• RBC,Placenta,Brain,Kidneys, Colon(Blood,Baby,BBB)

80. KidsLips-Kidneys,liver,pancreatic beta cells,gi small intstine
GLUT-2 found in B-cells, liver,
kidney and intestine epithelial cells:
•In the kidney and intestine responsible for
•Transporting glucose out of epithelial cells
during transepithelial transport.

81. 81

82. Father,Mother-Fats(adipose),Muscles(skeletal/cardiac)
Glucose Transporter 4 (GLUT4)
• Is activated by insulin
•Found in Insulin Sensitive Tissues
82

83. Insulin increases the rate of glucose
transport into certain cells by
•Recruiting GLUT4 to the plasma membrane
•From a storage pool.
83

84. 84

85. Other facilitative glucose
transporter are resident:
•In plasma membrane all the time
85

86. Diffusion across the cell membrane
is normally bidirectional
•Net diffusion is possible where there is
•Concentration, Electrical, Pressure gradient
86

87. 87

88. EMF = ± log
𝐶1
𝐶2
The electrical difference
that will balance a given
concentration difference
of univalent ions can be
determined from the
Nernst equation
EMF is Electromotive Force
88

89. 89

90. OSMOSIS
The most abundant substance
that diffuses through the cell
membrane is water
90

91. Osmosis is the process of net
movement of water caused by
•A concentration difference of water.
91

92. Net diffusion of water will occur
through semipermeable membrane
•From a solution low solute to higher solute
concentration
92

93. 93

94. Osmotic pressure
is the minimum pressure which
needs to be applied to a
solution to prevent the inward
flow of water across a
semipermeable membrane
94

95. The osmotic pressure exerted by particles in
a solution is determined by
• The number of particles per unit fluid volume.
• Not by the mass (size) of the particles.
• 1 osmole causes 19,300 mm Hg osmotic pressure.
95

96. OSMOLALITY viz OSMOLARITY
Osmolarity is the osmolar
concentration expressed as osmoles
per liter of solution rather than
osmoles per kilogram of water.
96

97. ACTIVE TRANSPORT
CONTINUED NEXT FOLDER
97