PHYSIOLOGY:PRELIMS [II: CELL MEMBRANE]

CELL MEMBRANE

Cell Membrane

- a.k.a. Plasma Membrane

-lipid bilayer

-most permeable – lipid soluble (utilize protein channel)

-composition outside is different inside (quantitative)

-important in cell survival

Functions of the Plasma Membrane

1. Separates the intracellular contents from the extracellular environment

2. Regulates the passage of substance into and out of the cells (selective permeability)

*Gatekeeper- Restricts the passage of some substances while permitting the passage of others (semi
permeability)

3. Maintains difference in composition and establishes ionic gradients between the intracellular and
extracellular compartments (permeability barrier)

4. Cell communication through neurotransmitters and hormone receptors and signal transduction
pathways

5. Cell recognition via cell surface antigen

6. Determination of cell shape by linking the cytoskeleton to the plasma membrane

7. Enzymatic activity

8. Tissue organization

MEMBRANE COMPOSITION:

Protein- 35%

Phospholipids- 25%

Cholesterol- 13%

Other lipids- 4%

Carbohydrates- 3%

MEMBRANE LIPIDS

 Lipid bilayer with fluid like properties

 Primarily responsible for the passive permeability of properties of the plasma membrane
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 Made up of:
o Phospholipids (major lipids)
o Cholesterol
o Glycolipids

Amphipathic

A. Polar head |hydrophilic portion|

B. Two non-polar hydrocarbon tails |hydrophobic|

PHOSPHOLIPIDS LEAFLET LOCATION

Phosphatidylcholine OUTER

Spingomyelin OUTER

Phosphatidyethanolamine INNER

Phophatidylserine INNER

Phophatidylinositol INNER

Cholesterol

-also a major component of the plasma membrane

-stabilize the membrane at room temperature

-functions as a “fluidity buffer” (temperature and its lipid compositions – unsaturated fatty acyly chains)

MEMBRANE PROTEINS

3 Major types:

a. Integral /Intrinsic membrane proteins

b. Peripheral or Extrinsic membrane proteins

c. Lipid anchored membrane proteins

Integral /Intrinsic Membrane Proteins

 Embedded in phospholipid layer

 Most span entire membrane |transmembrane proteins|; others anchored to one of the
monolayer
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Peripheral Membrane Proteins

 May associate with the polar group of membrane lipids

 Commonly bind to integral or lipid-anchored proteins

Lipid-Anchored Membrane Proteins

 Covalently attached to a lipid molecule by lipid anchors

MEMBRANE CARBOHYDRATES

 Glycolipids and glycoproteins with covalently bound oligosaccharide chains facing the exterior
 Form a sugar coating on the surface of eukaryotic cells
(glycocalyx)- single layer, provides integrity
 Give most cells an overall negative cell surface charge
 Attach cells to one another through glycocalyx
 Act as receptors
 Some enter into immune relations

EPITHELIAL STRUCTURES

 Contain epithelial cells arranged in sheets (external – internal environment)

 Functions:
-establish barrier to microorganism
-prevent loss of water
-maintenance of a constant internal environment
-regulated vectorial transport

MEMBRANE JUNCTIONS

 Cells are surrounded by extracellular fluid or matrix

 Some cells float freely |e.g. red blood cells in blood|
 Most cells are organized and packaged together
 Cells must be able to
o Communicate with each other
o Stay bound to other cells and the extracellular matrix

3 MAJOR TYPES OF MEMBRANE JUNCTIONS:

A. Tight or Occluding Junctions

 a.k.a occluding junctions or zonula occludens
 provide the tissue with strength and stability
 requires transmembrane proteins
o occludins
o JAMs
o Claudins

B. Anchoring Junctions
 Cell-cell junctions
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o Desmosomes
o Adherens junctions
 Cell-matrix junctions
o Focal adhesions
o Hemidesmosomes

COMPONENTS OF ANCHORING JUNCTIONS

 Intracellular anchor proteins

 Transmembrane adhesion or linker proteins (TLP)
- Integrins (cell-matrix) or cadherins (cel-cell)
 Cytoskeleton elements

C. Gap Junctions
 a.k.a communicating junctions
 Form cytoplasmic tunnels for diffusion of small molecules between two neighboring cells
 Provide low-resistance connection
 Made up of connexons
o Made up of connexin or pannexin protein subunits

ELECTRICAL SYNAPSE OR GAP JUNCTION

 Occurs between neurons and glial cells

 Acts as low-pass filters
 Observed in cardiac and unitary smooth muscle cells
 Couple cells both electrically and chemically
 More permeable than membrane channels

FLUIDS AND ELECTROLYTES

Here is a useful mnemonic:

The 60:40:20:15:5 rule. Memorize it.

 Total Body Water 60% of body weight

 Intracellular fluid 40% of body weight
 Extracellular fluid 20% of body weight
 Interstitial Water 15% of body weight
 Plasma 5% of body weight

FLUID OSMOLARITY

ECF – Extracellular Fluid (synovial fluid, CSF, etc)

(Interstitial and intravascular fluid)

Na+ - major determinant of ECF osmolarity – 90% of ECF

 PHYSIOLOGY:PRELIMS [II: CELL MEMBRANE]

Plasma Osmolarity

= 2 (Pasma [Na+])

= 2 (145) = 290 mOsm

CONCENTRATION OF SOLUTION

 OSMOLALITY (mOsm/kg of water)

o Number of osmoles per kg of solvent
o Not affected by volume of solutes and temperature
o Mass of water is difficult to measure
o Normal osmolality = 280 mOsm/kg of H2O(isoosmolal)
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 OSMOLARITY (mOsm/L of solution)

o number of osmoles per liter of solution
o affected by voume of solutes and temperature
o normal = 280 – 300mOsm/L (isoosmolar)
- 0.9% NaCl solution
- 5% dextrose

MEMBRANE TRANSPORT PROTEINS

 Water Channels
 a.k.a Aquaporins (AQPs)
 main route for water movement
 widely distributed with 12 isoforms
 water movement can be regulated by changing:
o number AQPs
o permeability (gating) – pH
 Ion Channels
 Widely distributed
 Important in excitable cells
 Highly selective of non selective
 Can be inward or outward rectifier
 Exhibits gating
 Solute Carriers
 > 40 types (>300 specific transporters)
 Types:
 Uniporters
 Symporters (co-transporters)
 Antiporters (counter-transporters or exchangers)
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 ATP Dependent Transporters

 Uses ATP to move substances
 Types:
 ATPase ion transporters
o P type
o V type
 ATP-binding Cassette (ABC)

MEMBRANE TRANSPORT

A. PASSIVE TRANSPORT
a. Diffusion
i. Simple
ii. Facilitated
b. Osmosis
c. Filtration
d. Solvent Drag

B. ACTIVE TRANSPORT
a. Primary Active Transport
b. Secondary Active Transport
i. Co-transport |Symport|
ii. Counter transport |Antiport|

C. VESICULAR TRANSPORT
a. Endocytosis- inner
i. Phagocytosis- larger subs
ii. Pinocytosis- smaller subs
b. Exocytosis- outer
c. Transcytosis

D. EPITHELIAL TRANSPORT
a. Paracellular- in between the cell
b. Transcellular- through the cell
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TRANSPORT OF SUBTANCES THROUGH A MEMBRANE

PASSIVE TRANSPORT ACTIVE TRANSPORT

Transport substances along an electrochemical Transport substances AGAINST an
gradient |concentration, pressure of electrical electrochemical gradient |concentration,
gradient| pressure or electrical gradient|

Downhill movement Uphill movement

|-| energy |+| energy

|-| carrier except facilitated diffusion |+| carrier

|-| net movement once equilibrium is reached Exhibits saturation kinetics

Exhibits stereospecificity
Exhibits competitive inhibition

PASSIVE TRANSPORT

Characteristics:

o Transport substances along an electrochemical gradient |concentration, pressure or electrical

gradient|
o Downhill movement
o (–) carrier except facilitated diffusion
o (–) energy (ATP)
o Stops once equilibrium is reached
o Examples : movement of sodium, potassium, calcium, chloride, glucose, water

SIMPLE DIFFUSION

o Spontaneous process by which a substance moves from a region of higher concentration to a

region of lower concentration due to inherent kinetic energy |random motion|

FICK’S FIRST LAW OF DIFFUSION

J = -DA|triangle C over triangle X|

J- Net rate diffusion
D – diffusion coefficient
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A – Area available for diffusion

C – Concentration difference across the membrane
X- thickness of membrane
Negative |-| - movement occurs from higher to lower concentration

J= D= A= C (CO – Ci) = X

CO2 (has 20x diffusion coefficient) diffuse faster than O2

What affects the diffusion coefficient?

 Oil/water partition coefficient / lipid solubility
 Molecular size
 Temperature
 Viscosity
𝐿𝑆𝑇
D= D = LS = T= mw = V
𝑚𝑤 𝑉
Factors that will INCREASE (DIRECTLY PROPORTIONAL) diffusion rate

 Lipid solubility
 Temperature
 Area
 Concentration gradient
 Diffusion coefficient
 Protein channel

Factors that will DECREASE (INVERSELY PROPRTIONAL) diffusion rate

 Thickness of membrane
 Size of substance
 Viscosity of medium

Substances that most permeable to least permeable:

1. small and lipid soluble non polar

2. small, water soluble but uncharged
3. large, polar uncharged (glucose)
4. small, polar and charged
5. large, polar and charged (proteins) – can’t pass the membrane

Diffusion of water soluble substances

 Water and very small uncharged water-soluble molecules and ions can pass through the
membrane much more rapidly then would be predicted by their lipid solubility
o Uncharged molecules can pass between adjacent phospholipid molecules without
dissolving in the bilayer
o Protein channels (water molecules and ions)
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SIMPLE DIFFUSION (non carrier mediated) – the more you increase the substance the more you increase
the diffusion

FACILITATED DIFFUSION – movement of solvent – carrier mediated diffusion

 Transport of substances down their concentration or electrochemical gradient using carrier

proteins
 Does not require energy (ATP)
 Carried mediated diffusion
 Example: glucose transporter, movement of sodium and calcium into the cell

LIMITATIONS OF ACTIVE TRANSPORT:

 Exhibits saturation kinetics

 Exhibits sterospecificity
 Exhibits competitive inhibition

------In facilitated diffusion the more you increase the substance the more you increase the diffusion
but if you reach the maximum aount you will reach the Vmax

OSMOSIS

 Net diffusion of water (solvent) across the membrane from higher concentration to lower
concentration of water (lower concentration of solute to higher concentration of solute) –
diffusion from higher to lower/lower to higher form of solute
 Passive movement of water across a semi- permeable membrane down its concentration
gradient (net diffusion of water across a membrane)
 Occurs through aquaporins
 Requires:
o Concentration gradient for a solute across the membrane
o Relative impermeability of the membrane to the solute
o Osmotic gradient (there should be equal distribution of solute; membrane should not be
permeable to solute/permeable to solvent)
o Membrane should be permeable to water
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OSMOTIC PRESSURE

 Measured in atmospheres van’t Hoffs law

 Amount of pressure required to stop movement of water into solution
 Dependent on the number of dissolved particles not the mass particles in the solution
 Must take into account the ionization of the solute
 Not dependent on the mass of solute, but into the number of particles

Dependent not on the mass but on the number of particles

Ex. 100g Glucose / 100g NaCl ->greater (2 particles Na and Cl)
Greater number of particle = greater the osmotic pressure

ONCOTIC PRESSURE – osmotic pressure generated by large molecules, normally 26-28 mmHg (28mmHg
= 1.4mOsm/kg H2O)

RBC
Hypotonic solution – cells will swell - < 300
Hypertonic solution – cells will shrink - >300
Isotonic – normal/no change- 280 – 300

Hemolysis – rupture of cells

OSMOLARITY (“tonicity” – should be equal in and out of the cell) AND CELL VOLUME

 RBCs
o Osmometer – measure osmolarity in cell
 Impermeant solutes – impermeable solute
 Unable to pass through membrane |e.g Na, Cl, K|

FILTRATION –movement across the membrane driven by hydrostatic pressure

 Substances and solvent move across the membrane driven by a hydrostatic pressure gradient.
 All substances can move
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 Capillary membrane

ACTIVE TRANSPORT

 Transport substances AGAINST (movement from lower to higher – carrier mediated – needs
ATP) an electrochemical gradient |concentration, pressure or electrical gradient|
 Uphill movement
 |+| energy - ATP
 |+| carrier
 Exhibits saturation kinetics
 Exhibits stereospecificity
 Exhibits competitive inhibition
Ex. Movement of: sodium, potassium, calcium, chloride

Primary and Secondary Active Transport - both active and exhibit same characteristic of active
transport thus;

PRIMARY ACTIVE TRANSPORT

- you can transfer 1 or more substances
- ATP (direct) - Directly linked to a cellular metabolism |ATP|
- All transported substances must be against chemical gradient

Examples
1. Na+-K+ pump ATPase
 Efflux of Na+ is NOT PRIMARY TRANSPORT
 Always located in the vasolateral
2. Ca++ pump ATPase (Sequestration of Ca++)
 Present and release of calcium on sarcoplasmic reticulum is NOT PRIMARY ACTIVE TRANSPORT
 Hydrolize ATP

3. H+K+ pump ATPase

 This is the one inhibited by proton pump; omeprazole = no acid production

SECONDARY ACTIVE TRANSPORT

 Linked to energy indirectly
 Uses the ion concentration gradient established by primarily active transport to fuel the uphill
movement of substances
o Strong inward gradient for NA due to Na-K ATPase pump which acts as a storehouse of
energy

 You can only transfer 2 or more

 ATP (indirect)
 One = along electrochemical gradient; Rest = against electrochemical gradient

Example: In your GIT small intestine (major absorptive area) lined by epithelial cell. GIT 2 membranes: 1
facing lumen (luminal membrane) one is facing blood (basolateral membrane) If I will transport glucose,
I can’t transport it without sodium.
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Glucose is never absorbed without Na+

Co transport or symport – moving in same direction

Countertransport or antiport – moving in different direction
Ex. Transport Na+ in kidney; you want to transport H+ out but you need the help of Na+

TRANSPORT OF SUBSTANCES ACROSS BUT NOT THROUGH A MEMBRANE

VESICULAR TRANSPORT
 Movement of large substances |proteins, polypeptides| across but not through the membrane
 Via the formation of vesicles which detach from or fuse with the plasma membrane
 Portion of membrane furrows inward or projects outward, encloses substance and brings it into
cell in the form of membrane- bound vesicles

ENDOCYTOSIS – moving in – move substances into the cell

 Phagocytosis “cell eating” – often receptor-

mediated
o Uptake particulate material, LARGE
o Important feature in the immune system
Ex. Phagocyte eating bacteria, bacterial, dead
tissue

 Pinocytosis “Cell drinking” – non-specific transport

of small molecules – prominent feature observed
across the capillary (ex. ECF,soluble material)
o Uptake of ECF and soluble material, SMALL
o Often begin at clathrin-coated pits
o Receptor mediated transport – a receptor is needed, this will contract and form a vesicle
to transport substance, bind it with receptor, membrane will invaginates and form a
vesicle

TYPES OF ENDOCYTOSIS
 RECEPTOR – MEDIATED
- transport of specific substance into the cell
- involves binding of substance with specific receptor
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-requires accessory proteins (adaptin, clathrin, GTPase)

 CLATHRIN – MEDIATED
- Includes of accumulation of clathrin
- May or may not require dynamin
- Plays a major role in synaptic function
Ex. Nerve growth factor & LDL

 CAVEOLAE – DEPENDENT UPTAKE

- Involve rafts and formation of caveolae (caveolin)

EXOCYTOSIS – moving out

 Ejection of molecules from cells / secretion of molecules from cells
 Resembles endocytosis in reverse direction
 Membrane bound vesicles in the cytoplasm fuse with the plasma membrane and release their
contents to the outside of the cell
 Usually Ca++ (calcium) dependent process (except in the release of rennin and parathyroid
secretion)
EXAMPLES:
 Neurotransmitter release from nerve endings
 Release of secretory products of cells |pancreatic enzymes|

EPITHELIAL TRANSPORT – a.k.a cellular sheet

- transport that move substances across epithelial surface

PATHWAYS FOR TRANSPORT:

a. Transcellular

o Transport through the cell passing the apical and basolateral membrane
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o Na+ -K+ ATPase located in basolateral membrane

o Fuels secondary transport of nutrients in apical membrane

b. Paracellular

o Transport occurs between two adjacent cell

o Limited by tight junction
o Only true for water and small substances