Physiology about ''Transport Across cell Membrane''.

1. TRANSPORT ACROSS CELL
MEMBRANE
Dr.PARAMJEET KAUR

2. LEARNING OBJECTIVE
• What is the importance of transport across
membrane.
• What are the various ways of transport.
• To understand the concept of
Diffusion,Osmosis, Active transport,
Endocytosis, Exocytosis and Pinocytosis.
• Various abnormalities of transport across
membranes.

3. IMPORTANCE OF TRANSPORT
• To communicate ECF with ICF.
• Movement of various ions across
mebrane.
• To maintain homeostasis.
• Protects cell from various harmful
substances.
• Removal of waste products
• Movements of various hormones and
substances from site of formation to site of
use.

4. PERMEABILITY OF DIFFERENT MOLECULES
CHARGED
POLAR
MOLECULES
LARGE
UNCHARGED
POLAR
MOLECULES
SMALL
UNCHARGED
POLAR
MOLECULES

6. DIFFUSION
• Any solute will tend to uniformly occupy
the entire space available to it. This
movement, known as diffusion, is a result
of the spontaneous Brownian (random)
movement that all molecules experience.
• Example- drop of ink placed in glass of
water

7. DIFFUSION- Movement of molecules from
higher concentration to lower concentration till
equilibrium is reached.

8. FICKS LAW OF DIFFUSION:
J = PA (Co - Ci)
•Describes the diffusion of any uncharged
solute in water.
• J= Rate of diffusion
• P = Permeability coefficient
•(Co - Ci) = Difference in concentration
across the membrane
• A= Surface area of the membrane.

9. SIMPLE DIFFUSION
TWO PATHWAYS :
1. Through the interstices of the lipid bilayer
if the diffusing substance is lipid-
soluble.Example-oxygen, nitrogen,
carbon dioxide, and alcohols.
2. Through watery channels that penetrate
all the way through some of the large
transport proteins.Protein “pores” called
aquaporins that selectively permit rapid
passage of water through the membrane.

10. The regulation and function of aquaporins (AQPs) in the
collecting-duct cells to increase water reabsorption. Vasopressin binding to its receptor
increases intracellular cAMP via activation of a Gs protein (not shown) and subsequent
activation of adenylate cyclase. cAMP increases the activity of the enzyme protein kinase
A (PKA). PKA increases the phosphorylation of specific proteins that increase the rate of
the fusion of vesicles (containing AQP2) with the apical membrane. This leads to an
increase in the number of AQP2 channels in the apical membrane. This allows increased
passive diffusion of water into the cell. Water exits the cell through AQP3 and AQP4,
which are not vasopressin sensitive.

11. FACTORS AFFECTING DIFFUSION
• Concentration gradient
• Size of molecule
• Surface area
• Solubility
• Temperature
• Diffusion medium

12. SIMPLE DIFFUSION- ION CHANNEL

13. MEDIATED TRANSPORT SYSTEM:
• Amino acids and glucose, are able to cross
membranes yet are too polar to diffuse through
the lipid bilayer and too large to diffuse through
channels. The passage of these molecules and
the non diffusional movements of ions are
mediated by integral membrane proteins known
as transporters.
• Depends on conformational changes in
transporters.
• ligand-gated ion channels
• voltage-gated ion channels
• mechanically gated ion channels

15. • EXAMPLE - FACILITATED
DIFFUSION : GLUT (Glucose
transporters)
• Factors determining magnitude of
solute flux :
• solute concentration
• affinity of the transporters for the solute
• number of transporters in the membrane
• rate at which the conformational change in the
transport protein occurs.

17. OSMOSIS
• Water is a polar molecule and yet it diffuses
across the plasma membranes of most cells
very rapidly.
• Process by which water moves passively
across a semipermeable membrane, driven by
a difference in water concentration between
the two sides of the membrane.
• This process is mediated by a family of
membrane proteins known as aquaporins that
form channels through.

18. • Example an individual who is dehydrated,
the numbers of aquaporins in the
membranes of the kidney epithelial cells
will increase; this will permit additional
water to move from the urine that is being
formed in the kidney ducts back into the
blood. That is why the volume of urine
decreases whenever an individual
becomes dehydrated.

19. DEMONSTRATION OF OSMOTIC
PRESSURE CAUSED BY OSMOSIS AT A
SEMIPERMEABLE MEMBRANE

20. TYPES OF TRANPORT MOLECULE

21. PRIMARY ACTIVE TRANSPORT -
Na+k+ATPase Pump

22. SODIUM POTTASIUM PUMP

23. PRIMARY ACTIVE TRANSPORT
1) transporter with an associated molecule of ATP, binds 3 sodium ions at high-affinity
sites on the intracellular surface of the protein. Two binding sites also exist for K+, but at
this stage they are in a low-affinity state and therefore do not bind intracellular K+.
(2) Binding of Na+ results in activation of an inherent ATPase activity of the transporter
protein, causing phosphorylation of the cytosolic surface of the transporter and releasing
a molecule of ADP.
(3) Phosphorylation results in a conformational change of the transporter, exposing the
bound Na+ to the extracellular fluid and, at the same time, reducing the affinity of the
binding sites for Na+. The Na+ is released from its binding sites.
(4) The new conformation of the transporter results in an increased affinity of the two
binding sites for K+, allowing two K+ to bind to the transporter on the extracellular
surface.
(5) Binding of K+ results in dephosphorylation of the transporter. This returns the
transporter to its original conformation, resulting in reduced affinity of the K+ binding sites
and increased affinity of the Na+ binding sites. K+ is therefore released into the
intracellular fluid, allowing additional Na+ (and
ATP) to be bound at the intracellular surface
(1) Ca2+- ATPase; (2) H+-ATPase; and (3) H+/K+-ATPase..

24. SECONDARY ACTIVE TRANSPORT
COUNTER-TRANSPORT

25. SECONDARY ACTIVE TRANSPORT
CO- TRANSPORT

26. EXAMPLES :
• SYMPORT / CO TRANSPORT :
1.Sodium Glucose
2.Sodim Iodide
• ANTIPORT / COUNTER TRANSPORT :
1.Sodium Pottasium
2.Sodium Bicarbonate
3.Sodium calcium counter transport
4.Sodium hydrogen counter transport
5.Sodium magnesium counter transport
6.Calcium magnesium counter transport
7. Calcium Potassium counter transport

28. SECONDARY ACTIVE TRANSPORT

29. • Membrane protein molecules interrupt the
continuity of lipid bilayer,constituiting an
alternative pathway through the cell
membrane.
• Many of these penetrating proteins can
function as transport proteins.
• Some proteins have watery spaces all the
way through the molecule and allow free
movement of water, as well as selected ions
or molecules;these proteins called carrier
proteins.

30. • other carrier proteins, bind with molecules
or ions that are to be transported, and
conformational changes in the protein
molecules then move the substances
though the interstices of the protein to the
other side of the membrane.
• channel proteins and carrier proteins are
usually selective for the types of molecules
or ions that are allowed to cross the
membrane.

31. • Transport through the cell
membrane,either directly through the lipid
bilayer or through the proteins ,occurs via
one of two basic processes, diffusion or
active transport.
• Diffusion means random molecular
movement of substances molecule by
molecule, either through intermolecular
spaces in the membrane or in combination
withh a carrier protein. The energy that
causes diffusion is the energy of the
normal kinetic motion of matter.

33. Various Transport Mechanisms

35. ACTIVE TRANSPORT THROUGH
CELLULAR SHEETS :
• Intestinal epithilium
• epithelium of renal tubules
• epithelium of all exocrine glands
• epithelium of gall bladder
• membrane of choroid plexus of the brain

36. VESICULAR TRANSPORT
• Substances are moved in membrane-
bounded vesicles, transported substances
are enclosed in the vesicle lumen or
located in the vesicle.
• TYPES :
1. Endocytosis
2. Exocytosis
3. Pinocytosis

37. ENDOCYTOSIS AND EXOCYTOSIS

38. ENDOCYTOSIS
• Process by which macromolecules enter
the cell.
• The molecules which are not transported
by passive or active transport , those are
transported by endocytosis.
• Uses energy
• Cell membrane in- folds around food
particle
• This is how white blood cells eat bacteria

39. ENDOCYTOSIS

40. ENDOCYTOSIS
• Endocytosis is a general term for the
process in which a region of the plasma
membrane is pinched off to form an
endocytic vesicle inside the cell.
1. Fluid-phase endocytosis
2. Receptor-mediated endocytosis

43. ENDOCYTOSIS TYPES:
• Fluid-phase endocytosis:nonspecific
uptake of the ECF and all its dissolved solutes.
The material is trapped inside the endocytic
vesicle as it is pinched off inside the cell.
• Receptor-mediated endocytosis more
efficient process, which uses receptors on
the cell surface to bind specific molecules.
These receptors accumulate at specific
depressions known as coated pits.

44. • hormones, growth factors, and serum
transport proteins such as the iron carrier
transferrin. Foreign substances, such as
diphtheria toxin and certain viruses, also
enter cells by this pathway

45. EXOCYTOSIS
• Vesicles containing material for export , such as
secretory granules, are targeted to cell
membrane.Two exocytic pathways:
1. Constitutive -secretion of mucus by goblet
cells in the small intestine.
2. Regulated- Macromolecules are stored inside
the cell in secretory vesicles, these vesicles
fuse with the cell membrane and release their
contents only when specific extracellular
stimulus arrives at the cell membrane.
• “on-demand” secretion of many specific
hormones, neurotransmitters, and digestive
enzymes

46. MECHANISM OF PINOCYTOSIS

47. DIGESTION OF SUBSTANCES IN
PINOCYTIC OR PHAGOCTIC VESICLES

48. CHANNELOPATHIS
• CYSTIC FIBROSIS MUTATIONS

49. Muscle membrane exitability
CALCIUM CHANNEL
Hypokalemic Periodic
paralysis
sodium channel
hyperkalemic
periodic paralysis
SODIUM CHANNEL
Paramyotonia
Congenita
Mode of
inheritance
AD AD AD
Age of onset Adolesence Early childhood Early childhood
attacks are provoked
by by meals high in
carbohydrates/sodium
lasting 30 min to 4
hrs
2- 24 hrs, severe
enough to require
emergency room
treatment
affects proximal >distal
limbmuscles
affects proximal
muscles,sparing
bulbar
weakness may take 24
hrs to resolve,life
threatening cardic
arrhythmias may occur
attacks precipitated
by rest following
exercise and fasting
sensory and motor
nerve conduction
studies - normal
midst attack -motor
conduction studies-
reduced motor
amplitude

50. CALCIUM
CHANNEL
Hypokalemic
Periodic paralysis
sodium channel
hyperkalemic
periodic paralysis
SODIUM CHANNEL
Paramyotonia
Congenita
mutations of voltage
gated sodium
channel
SCN4A gene
mutations of voltage
gated sodium channel
acetazolamide(125-
1000mg /d)
mexiletine
oral administration of
glucose
/carbohydrates
hastens recovery
prophylactic -
thiazides(chlorthiazide
250-1000mg/d)
Mexilitine

51. POTTASIUM CHANNEL
ANDERSEN-TAWIL SYNDROME
(RARE DISEASE)
Mode of inheritance AD
Age of onset Early childhood
mutation of potassium channel (kir2.1)
episodic weakness,cardiac
arrhythmias, dysmorphic
features(short statures,
scoliosis,clinodactyly, hypertelorism,
small or prominant low set ears,
micrrognathia, and broad forehead
cardiac arrhythmia-life threatening
QT prolongation , ventricular
ectopy,ventricular arrhythmias
acetazolamide decrease attack
frequency and severity

52. SUMMARY
• Membranes are very dynamic structures .
• Certain hydrophobic molecules freely
diffuse across the membrane.
• For other molecules various type of
channels,carrier proteins and pumps are
available.
• voltage gated ion channels are employed
to move charged molecules.
• various mutations in the channels lead to
diseases.