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Membrane Transport
By
Dr. Mudassar Ali Roomi (M.B; B.S., M. Phil.)
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Factors affecting rate of diffusion across a
selectively permeable membrane
1. Effect of conc. difference across membrane (directly)
2. Effect of temperature (directly)
3. Membrane permeability (directly)4. Lipid solubility of the substance
5. Water solubility of the substance
6. Size of molecules (inversely)
7. Effect of pressure difference across membrane (directly)8. Effect of membrane electrical potential (Nernst potential)(directly)
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Effect of conc. difference on net diffusion
through a membrane:
The rate at which the substance diffuses inward is directly proportional tothe concentration difference of molecules across the membrane
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Effect of membrane electrical potential on diffusion
of ions-
the Nernst Potential Electrical potential if applied across the
membrane Electrical charges of ionscause them to move through themembrane, even in the absence ofconcentration difference.
Conc. difference of ions develops in the
direction opposite to electrical potentialdifference.
Ions keep moving untill the 2 effectsbalance each other.
Definition: At normal body temperature,
the electrical difference that will balance agiven conc. difference of univalent ions iscalled as Nernst potential or equilibriumpotential.
EMF (mV) = +/- 61 log C1C2
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Effect of pressure difference across the
membrane:
Pressure inside the bloodcapillary is about 20 mmHggreater than outside.
So, at arterial end of the capillary
fluid is filtered out.
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Simple diffusion Vs Facilitated diffusion
Simple diffusion
Kinetic movement of
ions / molecules
through a membraneopening /
intermolecular spaces
without any interaction
with carrier proteins in
the membrane.
Facilitated diffusion
Requires interaction of a carrier
protein.
Carrier protein binds chemically
with & shuttles ions / moleculesthrough the membrane.
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2 pathways for simple diffusion
Through interstices of
lipid bilayer if diffusing
substance is lipid
soluble.
Through watery
channels that penetrate
all the way through
large transport proteins.
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Diffusion of lipid-soluble substances through
the lipid bilayer
The main factor effecting the rate of diffusionthrough lipid bilayer is lipid solubility of thesubstance.
Examples of highly lipid soluble substances:1. Oxygen,
2. nitrogen,
3. carbondioxide,
4. alcohol.
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Diffusion of water & other lipid-insoluble
molecules through protein channels:
Rapid penetration through
protein channels:
e.g., Water &
other lipid-insoluble(water-soluble & small
molecules).
Slow penetration:
Water-soluble larger
molecules.
e.g., urea molecule
(size is 20 % > water;
penetration is 1000 x < water).
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Diffusion through Protein Channels &
Gating of these channels:
Tubular pathways from ECF to ICF.
Simple diffusion from one side of membraneto other across protein channels.
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two important characteristics of protein
channels:
1. Often show selective
permeability for one
or more specific ions
or molecules.2. Most channels are
gated (can be opened
or closed by gates).
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Specificity of protein channels:
It is due to certain characteristics which are :
1. Channel diameter
2. Shape of the channel
3. Nature of electrical charges
4. Chemical bonds along their inner surfaces
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Characteristics of sodium-channel:
(specific for sodium ion passage)
0.3 to 0.5 nm diameter.
Strong Negative charge on inside.
Pull small dehydrated sodium ions inside, pullingsodium ions away from hydrating water molecules.
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Selective permeability of protein channels
for potassium ions:
Potassium channels:
Slightly smaller channels.
Not negatively charged.
Chemical bonds are different. Nostrong attractive forces pull sodiumions away from water molecules thathydrate them.
Hydrated form of potassium ion is
smaller, which can pass easilythrough small potassium channel.
Sodium channels:
Slightly bigger channels.
Negatively charged on inside.
Chemical bonds are different. Strongattractive forces pull sodium ions awayfrom water molecules that hydratethem.
Hydrated form of sodium ion is bigger,
as sodium ion attracts more watermolecules. They cannot pass throughsmall potassium channel, resulting intoselective permeability for a specific ion.
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Gating of protein channels
Significance:
Selective gating of sodium &potassium ions Controlof ion permeability of the
channels.
Mechanism:
Some gates are extensions of
transport protein molecule open and close byconformational change
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2 principal ways of opening & closing of gates
Voltage gating:
Molecular conformation of
the gate or
Molecular conformation of
the chemical bonds respond
to electrical potential across
cell membrane.
Chemical (ligand) gating:
Gates open by binding of a
chemical substance (ligand)
with the protein channel
conformational or chemical
bonding change in protein
molecule that opens /
closes the gate.
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Voltage & Ligand gating
Voltage gating:
When strong negative charge insidethe cell membrane (at RMP):
Sodium gates remain closed.
When inside of membrane loses its
negative charge:
Sudden opening of sodium gatesmassive sodium influxonset of action potential.
When inside becomes positive:
Potassium gates openpotassium efflux terminationof action potential.
Chemical / Ligand gating:
Example:
Effect of Acetylcholine onacetylcholine channel gate
opens passage of Na+ ions
Important at:
Neuromuscular junction
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4 types of gated channels
1. LIGAND GATED Some protein channel gates are opened by the binding of a chemical
substance with them.
e.g acetylcholine channels at neuromuscular junction
2. VOLTAGE GATED.
Some protein channel gates respond to electrical changes across the cellmembrane. e.g. sodium potassium channels.
3. PHOSPHORYLATED GATED CHANNELS
phosphorylation by ATP leading to opening and closing of these channels.
4. STRETCH OR PRESSURE GATED CHANNELS
Mechanical stretch of membrane results in channel opening.
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Facilitated Diffusion
Carrier mediated diffusion.
Carrier facilitates diffusion of the substance tothe other side.
Examples:
Glucose & most Amino Acids.
In presence of insulin, glucose transport through
GLUT-4 transporter increases 10-20-fold.
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Facilitated diffusion Vs Simple diffusion
Facilitated diffusion
Rate of diffusion reaches a
maximum (Vmax
), as the
concentration of diffusing
substance increases &
cannot rise greater than
Vmax
Simple diffusion
Rate of diffusion varies
directly with concentration
of diffusing substance
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What limits the rate of
facilitated diffusion: Saturation of carrier
molecules.
The rate of transport cannotbe greater than the rate at
which carrier protein molecule
can undergo change back &
forth between its 2 states.
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Primary active transport
Uphill transport with directuse of ATP.
Example: Sodium-potassium pump
Na/K pump is electrogenicin nature. How?
Other examples:
Primary active transport ofcalcium ions in ER muscle
Primary active transport ofhydrogen ions in gastricparietal cells and DCT ofnephrons.
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Sodium-potassium pump maintains cell
volume
Negatively charged proteins & organic molecules are present inside thecell.
They attract large numbers of potassium, sodium & other positive ions.
These molecules & ions osmosis of water to cell interior.
If not checked by sodium potassium pump cell will swell & burst.
Net filtration of 1 sodium to outside, so water is also transported outsideby osmosis.
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Secondary Active transport:
Co-transport & Counter-Transport
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Sodium Co-transport of
Glucose & Amino acids
Example:
Found at Epithelial cells ofintestinal tract.
Found at Renal tubules ofkidneys.
Significance:
To promote absorption of Glucose& Amino Acids into the blood.
Mechanism:
glucose / amino acid and sodiumattaches with binding sites ofcarrier. Conformational changeoccurs and transports both thesubstances in the same direction.
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Sodium Counter-Transport of Calcium &
Hydrogen Ions:
Transport in a direction opposite to the primary ion (Na+).
Examples:
Sodium-calcium counter-transport: (sodium in, & calcium
out.
Sodium-hydrogen counter-transport (proximal renal tubules,sodium from lumen tubular cell, & hydrogen into the
lumen
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Diffusion Vs Active Transport
Diffusion:1. Either through intermolecular
spaces in the membrane Or incombination with a carrierprotein.
2. Along the energy gradient.
3. From high to low concentration.
4. Energy of normal kinetic motion
of matter causes diffusion.5. Types: simple, and facilitateddiffusion.
6. Examples: transport of O2, CO2through the cell membrane
Active Transport:
1. In combination with a carrierprotein.
2. That allows the substance to
move against an energygradient.
3. Low concentration to highconcentration.
4. Kinetic energy + additionalsource of energy is required.
5. Types: primary and secondaryactive transport.
6. Examples: transport throughsodium-potassium ATPase
Pump.
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Active transport through cellular sheets:
Examples:
1. Intestinal epithelium
2. Renal tubularepithelium
3. Epithelium of exocrineglands
4. Epithelium ofgallbladder
5. Membrane of choroidplexus of brain etc.
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Active transport through cellular sheets
Mechanism:
1) Active transport occurs on
one side of transporting
cells in the sheet & then
2) Either simple diffusion or
facilitated diffusion
through the membrane on
opposite side of cell.
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Transport of sodium ions through epithelial
sheet of intestines, gallbladder & renal tubules
These cells are connectedtogether tightly at luminalpole by junctions calledkisses.
Luminal Brush border is
permeable to sodium ions &water (diffusion).
Then at basal & lateralborders, active transport ofsodium ions go to ECF /
Blood. High sodium ion conc.
gradient osmosis ofwater.
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Primary Active Transport:
Sodium-potassium pump: The sodium potassium pump is a complex
of two separate globular proteins.
Smaller protein might anchor the proteincomplex in the lipid membrane
The larger protein has three specificfeatures that are important for the
functioning of the pump:
1. It has three receptor sites for bindingsodium ions on the portion of the proteinthat protrudes to theinside of the cell.
2. It has two receptor sites for potassium ions
on the outside.
3. The inside portion of this protein near thesodium binding sites has ATPase activity.