Transport across cell membrane

Transfer of material and information across cell membrane

Cross-membrane movement of small molecules

Diffusion(passive and facilitated)Active transportCross membrane movement of large

moleculesEndocytosis Exocytosis

Signal transmission across membraneCell surface receptorsSignal transductionSignal internalization(coupled with

endocytosis)

Intracellular contact and communication

PassiveFacilitated diffusionActive transport

diffusion

Simple diffusionFacilitated diffusionSimple diffusion passive flow of a solute from higher to lower

concentration. It is limited by 1. Thermal agitation 2. Conc. Gradient3. solubility

Factors that affect net diffusion

Conc. gradient across the membraneElectrical potentialPermeability co-efficientHydrostatic pressure gradienttemperature

Substances move from a higher chemical concentration to a lower concentration i.e.in response to concentration gradient.

Rate of transport is directly proportional to concentration gradient.

Electrical gradient. molecules will move towards opposite

charges.in renal glomeruli the filtering membrane possesses negative charge and does not permit the negative charge proteins to pass through it.

Facilitated diffusion Passive transport of a fluid from higher to lower concentration mediated by specific transporter and ion channels.

Transporters may beSpecific proteins Transport may beUniportCo transportsymport

Cont….

Rate at which solutes enter cell by facilitated diffusion

Con.gradient across membraneAmount of carrier availableAffinity of the soluteRapidity of conformational changes

Hormones regulate the facilitated diffusion by changing the number of transporters available.

Insulin increases glucose transport in fats and muscles by recruiting transporters from an intracellular reservoir.

Ion-channels

Membranes have special devices called ion channels. Ion channels are transmembrane proteins that allow the selective entry of various ions.

These channels are for quick transport of electrolytes .

These channels usually remain closed but in response to a stimulus they open.

Some properties of ion channels

Comparison of transporters and ion channels

Voltage gated channels

They open or close in response to a change in membrane potential.

Example is sodium channel, potassium channel etc.

These are seen in nerve cells and involved in conduction of nerve impulses.

Sodium channel

Sodium channel has four subunits.Each subunit has alpha helical

transmembrane domain.A pore like structure is formed through which

ion pass.

Structure of the ion channel

K-channel

Ligand gated channels

They are opened by binding of effectors.The binding of a ligand to a receptor site on

the channels results in opening or closing of channels.

The ligand may be an extracellular signaling molecule or an intracellular messenger.

Examples are acetylcholine receptor or calcium channels etc.

Inophores

Microbes synthesize small organic molecules called inophores .

They shuttle for movement of ions across the membrane.

Hydrophilic centre.Surrounded by peripheral hydrophobic

region.Gramicidin fold-up to form hollow channels.

Valinomycin-a peptide inophore that binds potassium

Aquaporins

tetrameric trasmembrane proteins .Ten distinct aquaporins have been identified .Crystallography and other studies have

revealed how these channels permit the passage of water. But ,they exclude passage of ions and other proteins.

In essence the pores are too narrow to permit the passage of ions and proteins.

Active transport

Transport of a solute across the membrane against a concentration gradient with the expenditure of energy.

Na + K+ ATPase

Extracellular fluid has higher conc. Of sodium ions.

Intracellular fluid has higher conc. Of potassium.

Sodium ,potassium pump is an antiport pump.

Energy is provided by ATP.

H+ K+ ATPase

They are also called proton pumps.They exchange hydrogen for potassium.They are present in endosomes, lysosomes,

mitochondria and plasma membrane of certain cells.

Plasma membrane calcium pumps

They move calcium from cytosol into the extracellular fluid. By decreasing calcium conc. Within cytosol it prevents formation of relatively insoluble calcium phosphate which could hinder cytosolic function.

Endoplasmic reticulum calcium pumps

They move calcium from cytosol into the endoplasmic reticulum.

Secondary active transport

Molecules are transported into cells by active transport property of sodium potassium ATPase which keeps the cell interior deficient in sodium ions.

Plasma membrane is negatively charged on its interior.

Chemical and electrical gradient favour the movement of sodium ions into the cell interior.

Special transporter proteins acting as symporter bring about by facilitated diffusion a simultaneous movement of certain solutes along with sodium ion into the cell interior.

Later the sodium ions are pumped out of the cell by sodium potassium ATPase to lower its concentration within cell to help further movement of sodium along with its associated solute into the cell .

Thus the movement of solute into the cell depend upon the active transport property of sodium potassium ATPase.

For this reason this transport is secondary to

the movement of sodium ions.

Renal tubules

Action of sodium potassium ATPase causes a low content of sodium into the cell interior.

Movement of sodium ions into cell interior along its chemical and concentration gradient in association with glucose molecule is brought about by symporter namely sodium dependent glucose transporter.

Dissociation of sodium and glucose from their symporter in cell membrane.

Three sodium ions are moved into the extracellular fluid in exchange for two potassium by sodium potassium ATPase. Low sodium content of cell is maintained.

This allows further movement of more sodium ions into the cell from tubular lumen along with glucose.

The glucose molecule that has moved into the cell is transported across the outer cell membrane into the extracellular fluid by facilitated diffusion aided by glucose transporter-2.

Ion channels

Ion channels are made up of transmembrane subunits that come together to form a central pore through which ions pass.

Na+ channels

The opening of these channels causes Na+ influx.

Generation of action potential.Quinidine It blocks the sodium channel preventing

rapid rise in action potential in cardiac muscle cells.

It is used to treat cardiac arrythmias.

AmilorideBlocks Na+ channel present in apical

membrane of cells lining renal tubules. There will be excretion of more Na+ in urine.There will be excretion of more water in the

urine.Lowering of B.P.Used to treat hypertension

K+-channel

These channels on opening bring K+ efflux producing repolarization of excitable tissues; neuron and muscle cells.

MinoxidilBy opening k+ channels causes relaxation of

smooth muscles of arterioles leading to their dilation. This decrease in peripheral vascular resistance lowers the arterial B.P.

Chloride channel

Entry of chloride in cell interior will produce hyper polarization of cell membrane.

Gamma aminobutyric acid acts as an inhibitory neurotransmitter by opening of chloride channels.

This action of GABA is much increased by drugs of benzodiazepam family.

Calcium channel blockers

The cardiac muscles and most type of smooth muscle are dependent on transmembrane calcium influx for normal tone and contractile response.

In treatment of certain heart diseases and hypertension ,a reduction in contractility of cardiac muscle fiber and relaxation of smooth muscle in arteriolar wall is aimed at.

Calcium channel blocker drugs are used in treating angina pectoris and hypertension.

Transport of macromolecule

cells transport certain macromolecules across the plasma membrane by following mechanism

Endocytosis Exocytosis

Segment of plasma membrane invaginates enclosing small volume of extracellular fluid and its contents.

Fusion of endocytotic vesicle and primary lysosomes .

Formation of secondary lysosome.Macromolecules contents are digested to yield Amino acidsSimple sugarsnucleotide

Endocytosis requires energy ,usually from hydrolysis of ATP.

Phagocytosis occurs in specialized cells such as Macrophages and granulocytes.

Types of endocytosis

PhagocytosisPinocytosis.Pinocytosis is again of following typesFluid-phase pinocytosisAbsorptive pinocytosis

endocytosis

Phagocytosis occurs in specialized cells such as macrophages and granulocytes.

pinocytosis

Cell drinkingLeads to cellular uptake of fluid and fluid

contents.

fluid-phase pinocytosis

It is a non-selective process in which the uptake of solute by formation of small vesicle is proportionate to its conc. In extracellular fluid.

The formation of these vacuoles is extremely active process.

Absortive-pinocytosisIt is receptor

mediated endocytosis.

It is responsible for uptake of macromolecules for which there are binding sites on plasma membrane.

Fluid phase pinocytosis

It is a non-selective process in which the uptake of solute in the form of small vesicles is proportionate to its concentration in the extracellular fluid.

Formation of these vesicles is extremely active process.

Fibroblasts internalize their membrane at about one third rate of macrophages .

This process occurs rapidly than membranes are made.

The surface area and volume of cell don't change.so,membranes must be replaced by exocytosis.

Absorptive pinocytosis

It is also called receptor mediated pinocytosis.

It is responsible for the uptake of specific macromolecules for which there are binding sites on the plasma membrane.

Vesicles derived are formed by invagination of that are coated on the cytoplasmic side with a filamentous material and named as coated pits.

In many situations the protein clathrin is the filamentous material.

It has three limbed structure.

Fibroblast ,for example internalize their plasma membrane at about 1/3 rate of macrophages .this process occurs more rapidly than membranes are made.

The surface area and volume of cell do not change much, so membranes must be replaced by exocytose.

High affinity receptors permit the selective conc. Of ligand from the medium. It will minimize the uptake of fluid or soluble unbound macro molecules. It will markedly increase the rate at which specific molecules enter the cell.

Vesicles Coated pitsIt may be protein clatherin

in the filamentous material .

PIP2 plays important role in vesicle assembly.

Protein dynamin is necessary for pinching off clathrin coated vesicle

ExocytosisExocytosis releases certain macromolecules from the

cell.Signal is a hormoneLocal and transient changes in calcium concentration.Calcium triggers exocytosis.Molecules releasd have three facts.They are membrane proteins and associated with cell

surface.They can become part of extracellular matrix ,collagen

and Gag,s.They can enter extracellular fluid and signal other cells.

Low density lipoprotein molecule and its receptor are internalized by means of coated pits containing LDL receptor.

Exocytosis

Most cells release macromolecules by exocytosis.This process is involved in membrane remodelling.Components synthesized in ER and Golgi are

carried in vesicles that fuse with plasma membrane.

The signal for exocytosis is often a hormone.It brings a local change in calcium concentration.Calcium triggers exocytosis.Molecules released by exocytosis has three facts.They are membrane proteins and remain associated

with the cell surface.

They can become part of extracellular matrix.They can enter extracellular fluid and signal

other cells.Insulin ,parathyroid and catecholamine are

all packaged in granules processed within the cell.