MEMBRANE TRANPORT 2ND LECTURE BY DR. ROOMI

7/30/2019 MEMBRANE TRANPORT 2ND LECTURE BY DR. ROOMI

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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.

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MEMBRANE TRANPORT 2ND LECTURE BY DR. ROOMI