Membrane Transport

By

Dr. Mudassar Ali Roomi (M.B; B.S., M. Phil.)

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)

Effect of conc. difference on net diffusion through a membrane:

• The rate at which the substance diffuses inward is directly proportional to the concentration difference of molecules across the membrane

Effect of membrane electrical potential on diffusion of ions-

the “Nernst Potential” • Electrical potential if applied across the

membrane Electrical charges of ions cause them to move through the membrane, even in the absence of concentration difference.

• Conc. difference of ions develops in the

direction opposite to electrical potential difference.

• Ions keep moving untill the 2 effects

balance each other. • Definition: At normal body temperature,

the electrical difference that will balance a given conc. difference of univalent ions is called as Nernst potential or equilibrium potential.

• EMF (mV) = +/- 61 log C1

C2

Effect of pressure difference across the membrane:

• Pressure inside the blood capillary is about 20 mmHg greater than outside.

• So, at arterial end of the capillary fluid is filtered out.

Simple diffusion Vs Facilitated diffusion

• Simple diffusion

• Kinetic movement of ions / molecules through a membrane opening / 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 / molecules through the membrane.

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.

Diffusion of lipid-soluble substances through the lipid bilayer

• The main factor effecting the rate of diffusion through lipid bilayer is lipid solubility of the substance.

• Examples of highly lipid soluble substances: 1. Oxygen,

2. nitrogen,

3. carbondioxide,

4. alcohol.

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).

Diffusion through Protein Channels & Gating of these channels:

• Tubular pathways from ECF to ICF.

• Simple diffusion from one side of membrane to other across protein channels.

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).

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

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, pulling

sodium ions away from hydrating water molecules.

Selective permeability of protein channels for potassium ions:

Potassium channels: • Slightly smaller channels. • Not negatively charged. • Chemical bonds are different. No

strong attractive forces pull sodium ions away from water molecules that hydrate them.

• Hydrated form of potassium ion is smaller, which can pass easily through small potassium channel.

Sodium channels: • Slightly bigger channels. • Negatively charged on inside. • Chemical bonds are different. Strong

attractive forces pull sodium ions away from water molecules that hydrate them.

• Hydrated form of sodium ion is bigger, as sodium ion attracts more water molecules. They cannot pass through small potassium channel, resulting into selective permeability for a specific ion.

Gating of protein channels

Significance:

Selective gating of sodium & potassium ions Control of ion permeability of the channels.

Mechanism:

Some gates are extensions of transport protein molecule open and close by conformational change

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.

Voltage & Ligand gating

Voltage gating:

When strong negative charge inside the cell membrane (at RMP):

• Sodium gates remain closed.

When inside of membrane loses its negative charge:

• Sudden opening of sodium gates massive sodium influx onset of action potential.

When inside becomes positive:

• Potassium gates open potassium efflux termination of action potential.

Chemical / Ligand gating:

Example:

• Effect of Acetylcholine on acetylcholine channel gate opens passage of Na+ ions

Important at:

• Neuromuscular junction

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 cell

membrane. 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.

Facilitated Diffusion

• Carrier mediated diffusion.

• Carrier facilitates diffusion of the substance to the other side.

Examples:

Glucose & most Amino Acids.

In presence of insulin, glucose transport through GLUT-4 transporter increases 10-20-fold.

Facilitated diffusion Vs Simple diffusion

Facilitated diffusion

• Rate of diffusion reaches a maximum (V max), as the concentration of diffusing substance increases & cannot rise greater than Vmax

Simple diffusion

• Rate of diffusion varies directly with concentration of diffusing substance

What limits the rate of facilitated diffusion:

• Saturation of carrier molecules.

• The rate of transport cannot be greater than the rate at which carrier protein molecule can undergo change back & forth between its 2 states.

Primary active transport

• Uphill transport with direct use of ATP.

• Example: Sodium-potassium pump

• Na/K pump is electrogenic in nature. How?

• Other examples: • Primary active transport of

calcium ions in ER muscle • Primary active transport of

hydrogen ions in gastric parietal cells and DCT of nephrons.

Sodium-potassium pump maintains cell volume

• Negatively charged proteins & organic molecules are present inside the cell.

• 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 outside by osmosis.

Secondary Active transport: Co-transport & Counter-Transport

Sodium Co-transport of Glucose & Amino acids

Example: • Found at Epithelial cells of

intestinal tract. • Found at Renal tubules of

kidneys.

Significance: To promote absorption of Glucose

& Amino Acids into the blood. Mechanism: glucose / amino acid and sodium

attaches with binding sites of carrier. Conformational change occurs and transports both the substances in the same direction.

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

Diffusion Vs Active Transport

Diffusion: 1. Either through intermolecular

spaces in the membrane Or in combination with a carrier protein.

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 facilitated diffusion.

6. Examples: transport of O2, CO2 through the cell membrane

Active Transport: 1. In combination with a carrier

protein.

2. That allows the substance to move against an energy gradient.

3. Low concentration to high concentration.

4. Kinetic energy + additional source of energy is required.

5. Types: primary and secondary active transport.

6. Examples: transport through sodium-potassium ATPase Pump.

Active transport through cellular sheets:

Examples: 1. Intestinal epithelium

2. Renal tubular epithelium

3. Epithelium of exocrine glands

4. Epithelium of gallbladder

5. Membrane of choroid plexus of brain etc.

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.

Transport of sodium ions through epithelial sheet of intestines, gallbladder & renal tubules

• These cells are connected together tightly at luminal pole by junctions called “kisses”.

• Luminal Brush border is permeable to sodium ions & water (diffusion).

• Then at basal & lateral borders, active transport of sodium ions go to ECF / Blood.

• High sodium ion conc. gradient osmosis of water.

Primary Active Transport: Sodium-potassium pump:

• The sodium potassium pump is a complex of two separate globular proteins.

• Smaller protein might anchor the protein

complex in the lipid membrane

• The larger protein has three specific features that are important for the functioning of the pump:

1. It has three receptor sites for binding

sodium ions on the portion of the protein that protrudes to the inside of the cell.

2. It has two receptor sites for potassium ions

on the outside. 3. The inside portion of this protein near the

sodium binding sites has ATPase activity.