Human PhysiologyChapter 6: Movement of molecules across cell membranes

John Paul L. Oliveros, MD

Diffusion Molecules of any substance are in a continuous state of

movement or vibration The warmer the substance is, the faster its molecules

move The average speed of the “thermal motion” depends on

the mass of the molecule◦ Water= 2500km/h◦ Glucose= 850km/h

In solutions, molecules cannot travel very far before colliding with other molecules

The movement of molecules are random The random thermal movement of molecules will

redistribute solutes in a solution from regions of higher concentration to regions of lower concentration

Diffusion: movement of molecules from one location to another due to random thermal motion

Diffusion

Diffusion

Diffusion Flux

◦ amount of material crossing a surface in a unit of time

Net Flux◦ The difference between the 2

one-way fluxes◦ Determines the net gain/loss of

molecules from compartments separated by a membrane

◦ Always occur in the direction from higher to lower concentration

Distribution Equilibrium◦ The two one-way fluxes are

equal in magnitude but opposite in direction

◦ Net flux is equal to zero◦ No further changes in the

concentration of a substance in the 2 compartments will occur

DiffusionProperties of diffusion:

◦Three fluxes can be determined at any surface (2 opposite one-way fluxes; one net flux)

◦The net flux is the most important component in diffusion since it is the net amount of material transfered from one location to the other

◦The direction and the magnitude of the net flux are determined by the concentration difference The net flux always proceeds from regions of higher

concentration to regions of lower concentration The greater the difference of concentration between

any two regons the greater the magnitudeof the net flux

DiffusionFactors determining the magnitude of

the net flux at any given concentration difference◦Temperature

Inc. Temp inc. Speed of molecular movement inc. Net flux

◦Mass of the molecule Inc. mass dec. Speed of mol. Mov. dec net flux

◦Surface area Inc S.A. inc space for diffusion inc net flux

◦Medium of which the molecules are moving Air > Water

DiffusionDiffusion rate vs Distance

◦Diffusion times increase in proportion to the square of the distance over which the molecules diffuse

15ms 265 days

DiffusionDiffusion through

membranes◦ Magnittude of the

net flux is directly proportional to the difference in concentration across the membrane, the surface area of the membrane, and the membrane permeability constant

DiffusionDiffusion through the lipid bilayer

◦Major limiting factor of diffusion across membrane

◦Polar molecules disolve into cells slowly or not at all Organic molecules

◦Nonpolar molecules dissolve rapidly Can dissolve in the nonpolar regions of the

lipid membrane Oxygen, carbon dioxide, fatty acids,

steroid hormones

Diffusion Diffusion of Ions

through Protein Channels◦ Ions (Na+, K+, Cl -,

Ca++) diffuse faster in cells with more integral membrane proteins

◦ Integral proteins form channels

◦ Selectivity on passage of ions Diameter Polarity of surface

Diffusion Role of Electric Forces on

Ion Movement◦ Membrane potential

Separation of charges across the cell membrane

electric force that influences movemnt of ions across membranes

Same sign elcetric charges repel each other

Different sign charges attract each other

Most cellss are electrically negative atract + charged ion

◦ Electrochemical gradient Electrochemical difference

across a membrane Concentration difference +

electrical difference (membrane potential

Diffusion Regulation of Diffusion

through ion channels◦ Channel gating

Process of opening and closing ion channels

◦ Patch clamping Technique that helped study ion

channels

◦ Ligand sensitive channels Binding of specific molecules to

channel proteins produces allosteric or covalent changes of the protein

◦ Voltage-gated channels Changes in the membrane

potential causes movement of charged regions of the channel proteins

◦ Mechanosensitive channels Stretching the membrane affect

the conformation of some channel proteins

Mediated Transport SystemsTransporters/

carriers◦ Integral

membrane proteins that mediate the passage of large or polar molecules and non-diffusional movement of ions

◦ Factors determining magnitude of solute flux1. Extent to which

transporter binding sites are saturated

2. The number of transporters in a membrane

3. Rate of conformational change in the transport protein

Mediated Transport Systems

When transporters are reportedly almost saturated, the maximal transport flux depends on the rate of conformational change of the transporter to transfer its protein from one surface to the other

Mediated Transport SystemFacilitated

Diffusion◦ Uses a transporter to

move solutes downhill, from a higher to lower concentration until concentration between the 2 sides are the same

◦ Really doesn’t involve diffusion but end results are the same

◦ No energy is involved◦ E.g. Glucose transport

Mediated Transport SystemsActive Transport

◦ Uses energy to move a substance against its electrochemical gradient (uphill)

◦ Requires binding of the substance to the transporter in the membrane

◦ AKA pumps◦ Also exhibits

specificity and saturation

Active transport◦ Needs continuous input

of energy1. Alter the affinity of the

binding site on the transporter; higher affinity when facing one side of the membrane than the other

2. Alter the rates at which the binding site on the transporter is shifted from one surface to the other

◦ Two types: Primary active transport Secondary active

transport

Mediated Transport SystemPrimary active

transport◦ Transporter:

ATPase◦ ATP breakdown

and phosphorylation of ATPaseenergy

Events during active transport1. Exposure of binding

site to ECF2. Binding of solute to

the binding site3. Removal of the PO4

group of the transporter

4. Release of solute to ICF

5. Rephosphorylation of binding site as it agian exposed to ECF

Mediated Transport SystemsPrimary Active Transport

◦ Na, K-ATPase Present in all plasma

membranes High intracellular K+ and low

intracelluilar Na+ 1 ATP 3 Na+, out , 2K+ in

◦ Ca-ATPase In plasma membrane and

endoplastic reticulum

◦ H-ATPase In PM, mitochondria and

lysosomes

◦ H, K-ATPase In acid secreting cells of

stomach and kidneys

Mediated Transport SystemSecondary

Active Transport◦ Use ion

concentration gradient as energy source

Events during secondary active transport1. Altering the affinity

of the binding site for the solute

2. Altering the rate of at which the binding site is shifted from one surface to the other

3. Protein allosteric modulation due to ion binding

Mediated Transport SystemSecondary Active

Transport◦ Cotransport

Solute moves with same direction as ion

◦ Countertransport Solute move

opposite direction of ion

Mediated Transport SystemSecondary active

transport◦ Na+, Ca++

countertransport◦ Digitalis

Inhibits Na+,K+-atpase in heart muscle cells

Increase in IC Na+ Increase in IC Ca++ Increase in force of

contraction of heart muscles

Mediated Transport System

Mediated Transport system

Mediated Transport System

OsmosisWater

◦ Small polar molecule◦ 0.3 nm in diameter◦ Plasma membranes

10x more permeable to water than artificial membranes

◦ Aquaporins: Membrane proteins that

form channels where water can diffuse

Number differs in different membranesa

Can be alterted in response to various signals

Osmosis◦ Net diffusion of water

across membranes◦ Additon of solute

decreases concentration concentration difference flux

◦ Mol Wt of H20 = 18◦ 1L H20 =1kg◦ Conc. Of H20 in pure H20

= 1000/18 = 55.5M◦ 1 molecule of solute will

displace1 molecule of H20 Dec in H20 conc= conc of

solute 1M of glucose = 54.5 M H20

Osmosis The degree to which H20

conc is decreased by addition of a solute depends upon the number of particles (molecules/ions) of solute in a solution and not upon the chemical nature of the solute◦ e. g. Concentration of 1 mol

glucose solution = 1mol AA soultion= 1 mol urea solution

A molecule that ionizes in a solution decreases the water concentration in proportion to the number of ions formed◦ e.g. 1 M of MgCl++ lowers

water conc 3x than 1 M glucose

OsmosisOsmolarity

◦ Total solute concentration of a solution

◦ 1 osm = 1 molecule of particle in a solution

◦ 1M of glucose = 1osm◦ I M of NaCl = 2 osm◦ The higher the

osmolarity, the lower the water concentration

OsmosisMembrane

impermeable to solutes but permeable to water◦ Just like plasma

membrane◦ Equilibrium:

Equal concentrations in both compartments

Volume in expands in the compartment with more solutes

◦ if compartments are infinitely expandle, net transfer doesn’t create a pressure gradient

OsmosisMembrane impermeable to solutes

but permeable to water but non-expandable/limited expansion◦H20 moves to compartment with

more solutes increase in pressure of compartment oppose net water entry

◦Osmotic pressure: the pressure that must be applied to the solution to prevent the net flow of H2O into the solution

OsmosisExtracellular

osmolarity and cell volume◦ 85% of EC solutes

are Na++ and Cl-◦ Na++ moved out by

Na, K-ATPase pump◦ Cl- moved out by

secondary active-transport pumps

◦ Both ions behave as non-penetrating solutes

Intracellular◦ K+ and organic

molecules◦ Organic molecules are

large and polar, thus are non-penetrating

◦ K+ is moved preferably moved into cells by Na, K-ATPase pump

◦ Both intracellular extracellular osmolarity are kept at 300 mOsm

Osmosis

Endocytosis and ExocytosisEndocytosis:

◦ Folding of regions of PM small pockets IC vesicles

Exocytosis:◦ IC vesicles

fusion with PM release of contents EC

EndocytosisPinocytosis (cell drinking)

◦ Fluid endocytosis Enclosure of a small volume of

ECF

◦ Adsorptive endocytosis Molecules bind to membrane

CHONs and are carried along with ECF inside the cell when membrane invaginates

Phagocytosis (cell eating)◦ Large particles are

engulfed by cells◦ PM folds around the surface

of the particle so that little ECF is enclosed within the vesicles

Exocytosis Funtions:

◦ To replace portions of PM removed during endocytosis

◦ Route for impermeable CHONs getting outside cell

New CHONs endoplasmic reticulum processing in golgi apparatus vesicles plasma membrane released to ECF

Release triggered by stimuli that leads to an increase in cytostolic concentration in cells

Stimuli opens Ca++ channels in PM and/or membranes of IC organelles

Increase in Ca++ activates CHONs requiredfor the vesicle membrane to fuse with the PM and secrete contents EC

For rapid secretion of materials in response to stimulus

Epithelial TransportEpithelial cells

◦ Line hollow organs and tubes

◦ Regulate absorption and secretion of substances across membranes

Luminal/Apical membrane◦ Surface facing a

hollow or fluid filled chamber

Basolateral membrane:◦ Adjacent to network of

blood vessels◦ Opposite apical

membrane2 pathways crossing

the epithelium◦ Paracellular pathway

Diffusion between adjacent cells

Limited due o tight junction membranes

◦ Transcellular pathway Movement across cell from

apical to basal membrane

Epithelial TransportTranscellular

Transport◦ Through diffussion and

mediated transport◦ Different transport and

permeability characteristics between apical and basement membranes

◦ Substances undergo active transfusion across the overall epithelial layer

◦ e.g. GI tract, kidneys, glands

Epithelial Transport

GlandsGlands

◦ Secrete specific substances into the extracellular fluid or the lumen of ducts in response to appropriate stimuli

◦ Formed during embryonic development by the infolding of the epithelial layer of an organ’s surface

Types of Glands◦ Exocrine gland

Secretions flow through the ducts and are discharged into the lumen of an organ or the surface of the skin

e.g. Sweat glands, salivary glands

◦ Endocrine gland Ductless glands\ Secretions are released

directly on the interstitial fluid surrounding the gland cells

Secretions then diffuses into the blood carrying it to all of the body

GlandsEndocrine glands

◦ Hormones Major class of chemical

messengers

◦ Non-hormonal organic substances e.g. Liver: glucose, A.A.,

fats, CHONs,

Types of glandular secretions◦ Organic material

Synthesized by cells

◦ Salts and water From blood supplying the

tissue

GlandsGlands

◦ Undergo low basal rate of secretion

◦ Signal (nerve signals, hormones) augnmentation of secretions

◦ Mechanisms in increasing secretion:

◦ 1. increase rate of synthesis by increasing enzyme

◦ 2. providing Ca ++ for exocytosis

◦ 3. altering pumping rates of transporter or opening ion channels

Glands◦ Volume of

secretion increased by increasing Na+ pump activity or controlling the opening of Na+ channels in the PM

◦ Increase in Na+ in the epithelium increases flow of H20 by osmosis