This document discusses various mechanisms of transport across cell membranes, including: 1) Passive transport mechanisms like diffusion and facilitated diffusion of small molecules. 2) Active transport of ions and macromolecules against a concentration gradient using ATP. 3) Endocytosis and exocytosis for transport of large molecules and macromolecules across the membrane. 4) Specific transport proteins and ion channels that facilitate movement of substances in and out of cells.

1. Transport across cell membrane

3. Transfer of material and information across cell
membrane
 Cross-membrane movement of small
molecules
 Diffusion(passive and facilitated)
 Active transport
 Cross membrane movement of large
molecules
 Endocytosis
 Exocytosis

4.  Signal transmission across membrane
 Cell surface receptors
 Signal transduction
 Signal internalization(coupled with endocytosis)

5. Intracellular contact and communication
 Passive
 Facilitated diffusion
 Active transport

6. diffusion
 Simple diffusion
 Facilitated diffusion
 Simple diffusion
passive flow of a solute from higher to lower
concentration. It is limited by
1. Thermal agitation
2. Conc. Gradient
3. solubility

7. Factors that affect net diffusion
 Conc. gradient across the membrane
 Electrical potential
 Permeability co-efficient
 Hydrostatic pressure gradient
 temperature

8.  Substances move from a higher chemical
concentration to a lower concentration i.e.in
response to concentration gradient.
 Rate of transport is directly proportional to
concentration gradient.
 Electrical gradient.
 molecules will move towards opposite charges.in
renal glomeruli the filtering membrane possesses
negative charge and does not permit the negative
charge proteins to pass through it.

9. Facilitated diffusion
Passive transport of a fluid from higher to lower
concentration mediated by specific transporter and
ion channels.
Transporters may be
 Specific proteins
Transport may be
 Uniport
 Co transport
 symport

12. Cont….
Rate at which solutes enter cell by facilitated
diffusion
 Con.gradient across membrane
 Amount of carrier available
 Affinity of the solute
 Rapidity of conformational changes

13.  Hormones regulate the facilitated diffusion by
changing the number of transporters available.
 Insulin increases glucose transport in fats and
muscles by recruiting transporters from an
intracellular reservoir.

14. Ion-channels
 Membranes have special devices called ion channels.
Ion channels are transmembrane proteins that allow
the selective entry of various ions.
 These channels are for quick transport of electrolytes
.
 These channels usually remain closed but in
response to a stimulus they open.

15. Some properties of ion channels

16. Comparison of transporters and ion channels

17. Voltage gated channels
 They open or close in response to a change in
membrane potential.
 Example is sodium channel, potassium channel etc.
 These are seen in nerve cells and involved in
conduction of nerve impulses.

18. Sodium channel
 Sodium channel has four subunits.
 Each subunit has alpha helical transmembrane
domain.
 A pore like structure is formed through which ion
pass.

19. Structure of the ion channel

20. K-channel

21. Ligand gated channels
 They are opened by binding of effectors.
 The binding of a ligand to a receptor site on the
channels results in opening or closing of channels.
 The ligand may be an extracellular signaling
molecule or an intracellular messenger.
 Examples are acetylcholine receptor or calcium
channels etc.

22. Inophores
 Microbes synthesize small organic molecules called
inophores .
 They shuttle for movement of ions across the
membrane.
 Hydrophilic centre.
 Surrounded by peripheral hydrophobic region.
 Gramicidin fold-up to form hollow channels.

23. Valinomycin-a peptide inophore that binds
potassium

24. Aquaporins
 tetrameric trasmembrane proteins .
 Ten distinct aquaporins have been identified .
 Crystallography and other studies have revealed how
these channels permit the passage of water. But ,they
exclude passage of ions and other proteins.
 In essence the pores are too narrow to permit the
passage of ions and proteins.

25. Active transport
 Transport of a solute across the membrane against a
concentration gradient with the expenditure of
energy.

26. Na + K+ ATPase
 Extracellular fluid has higher conc. Of sodium ions.
 Intracellular fluid has higher conc. Of potassium.
 Sodium ,potassium pump is an antiport pump.
 Energy is provided by ATP.

28. H+ K+ ATPase
 They are also called proton pumps.
 They exchange hydrogen for potassium.
 They are present in endosomes, lysosomes,
mitochondria and plasma membrane of certain cells.

29. Plasma membrane calcium pumps
 They move calcium from cytosol into the
extracellular fluid. By decreasing calcium conc.
Within cytosol it prevents formation of relatively
insoluble calcium phosphate which could hinder
cytosolic function.

30. Endoplasmic reticulum calcium pumps
 They move calcium from cytosol into the
endoplasmic reticulum.

31. Secondary active transport
 Molecules are transported into cells by active
transport property of sodium potassium ATPase
which keeps the cell interior deficient in sodium
ions.
 Plasma membrane is negatively charged on its
interior.
 Chemical and electrical gradient favour the
movement of sodium ions into the cell interior.

32.  Special transporter proteins acting as symporter
bring about by facilitated diffusion a simultaneous
movement of certain solutes along with sodium ion
into the cell interior.
 Later the sodium ions are pumped out of the cell by
sodium potassium ATPase to lower its concentration
within cell to help further movement of sodium
along with its associated solute into the cell .

33.  Thus the movement of solute into the cell depend
upon the active transport property of sodium
potassium ATPase.
 For this reason this transport is secondary to the
movement of sodium ions.

34. Renal tubules
 Action of sodium potassium ATPase causes a low
content of sodium into the cell interior.
 Movement of sodium ions into cell interior along its
chemical and concentration gradient in association
with glucose molecule is brought about by symporter
namely sodium dependent glucose transporter.
 Dissociation of sodium and glucose from their
symporter in cell membrane.

35.  Three sodium ions are moved into the extracellular
fluid in exchange for two potassium by sodium
potassium ATPase. Low sodium content of cell is
maintained.
 This allows further movement of more sodium ions
into the cell from tubular lumen along with glucose.
 The glucose molecule that has moved into the cell is
transported across the outer cell membrane into the
extracellular fluid by facilitated diffusion aided by
glucose transporter-2.

38. Ion channels
 Ion channels are made up of transmembrane
subunits that come together to form a central pore
through which ions pass.

39. Na+ channels
 The opening of these channels causes Na+ influx.
 Generation of action potential.
 Quinidine
 It blocks the sodium channel preventing rapid rise
in action potential in cardiac muscle cells.
 It is used to treat cardiac arrythmias.

40.  Amiloride
 Blocks Na+ channel present in apical membrane of
cells lining renal tubules.
 There will be excretion of more Na+ in urine.
 There will be excretion of more water in the urine.
 Lowering of B.P.
 Used to treat hypertension

41. K+-channel
 These channels on opening bring K+ efflux
producing repolarization of excitable tissues; neuron
and muscle cells.
 Minoxidil
 By opening k+ channels causes relaxation of smooth
muscles of arterioles leading to their dilation. This
decrease in peripheral vascular resistance lowers the
arterial B.P.

42. Chloride channel
 Entry of chloride in cell interior will produce hyper
polarization of cell membrane.
 Gamma aminobutyric acid acts as an inhibitory
neurotransmitter by opening of chloride channels.
 This action of GABA is much increased by drugs of
benzodiazepam family.

43. Calcium channel blockers
 The cardiac muscles and most type of smooth muscle
are dependent on transmembrane calcium influx for
normal tone and contractile response.
 In treatment of certain heart diseases and
hypertension ,a reduction in contractility of cardiac
muscle fiber and relaxation of smooth muscle in
arteriolar wall is aimed at.
 Calcium channel blocker drugs are used in treating
angina pectoris and hypertension.

44. Transport of macromolecule
cells transport certain macromolecules across the
plasma membrane by following mechanism
 Endocytosis
 Exocytosis

45.  Segment of plasma membrane invaginates enclosing
small volume of extracellular fluid and its contents.
 Fusion of endocytotic vesicle and primary lysosomes
.
 Formation of secondary lysosome.
 Macromolecules contents are digested to yield
 Amino acids
 Simple sugars
 nucleotide

46.  Endocytosis requires energy ,usually from hydrolysis
of ATP.
 Phagocytosis occurs in specialized cells such as
Macrophages and granulocytes.

47. Types of endocytosis
 Phagocytosis
 Pinocytosis.
 Pinocytosis is again of following types
 Fluid-phase pinocytosis
 Absorptive pinocytosis

48. endocytosis
 Phagocytosis occurs in specialized cells such as
macrophages and granulocytes.

49. pinocytosis
 Cell drinking
 Leads to cellular uptake of fluid and fluid contents.

50.  fluid-phase pinocytosis
 It is a non-selective
process in which the
uptake of solute by
formation of small
vesicle is proportionate
to its conc. In
extracellular fluid.
 The formation of these
vacuoles is extremely
active process.
 Absortive-pinocytosis
 It is receptor mediated
endocytosis.
 It is responsible for
uptake of
macromolecules for
which there are binding
sites on plasma
membrane.

51. Fluid phase pinocytosis
 It is a non-selective process in which the uptake of
solute in the form of small vesicles is proportionate
to its concentration in the extracellular fluid.
 Formation of these vesicles is extremely active
process.
 Fibroblasts internalize their membrane at about one
third rate of macrophages .
 This process occurs rapidly than membranes are
made.

52.  The surface area and volume of cell don't
change.so,membranes must be replaced by
exocytosis.

53. Absorptive pinocytosis
 It is also called receptor mediated pinocytosis.
 It is responsible for the uptake of specific
macromolecules for which there are binding sites on
the plasma membrane.
 Vesicles derived are formed by invagination of that
are coated on the cytoplasmic side with a
filamentous material and named as coated pits.
 In many situations the protein clathrin is the
filamentous material.
 It has three limbed structure.

54.  Fibroblast ,for example
internalize their plasma
membrane at about 1/3
rate of macrophages .this
process occurs more
rapidly than membranes
are made.
 The surface area and
volume of cell do not
change much, so
membranes must be
replaced by exocytose.
 High affinity receptors
permit the selective conc.
Of ligand from the
medium. It will minimize
the uptake of fluid or
soluble unbound macro
molecules. It will markedly
increase the rate at which
specific molecules enter the
cell.
 Vesicles
 Coated pits
 It may be protein clatherin
in the filamentous material
.

55.  PIP2 plays important
role in vesicle assembly.
 Protein dynamin is
necessary for pinching
off clathrin coated vesicle

56. Exocytosis
 Exocytosis releases certain macromolecules from the cell.
 Signal is a hormone
 Local and transient changes in calcium concentration.
 Calcium triggers exocytosis.
 Molecules releasd have three facts.
 They are membrane proteins and associated with cell
surface.
 They can become part of extracellular matrix ,collagen
and Gag,s.
 They can enter extracellular fluid and signal other cells.

58.  Low density lipoprotein molecule and its receptor
are internalized by means of coated pits containing
LDL receptor.

60. Exocytosis
 Most cells release macromolecules by exocytosis.
 This process is involved in membrane remodelling.
 Components synthesized in ER and Golgi are carried
in vesicles that fuse with plasma membrane.
 The signal for exocytosis is often a hormone.
 It brings a local change in calcium concentration.
 Calcium triggers exocytosis.
 Molecules released by exocytosis has three facts.
 They are membrane proteins and remain associated
with the cell surface.

61.  They can become part of extracellular matrix.
 They can enter extracellular fluid and signal other
cells.
 Insulin ,parathyroid and catecholamine are all
packaged in granules processed within the cell.