Membrane transport- L1

Faisal I. Mohammed, MD, PhD

Resource: Guytons Textbook of Medical Physiology 12th edition.

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Objectives
List trans-membrane transport mechanisms (passive and active) Describe passive mechanisms (simple diffusion, facilitated diffusion, osmosis, bulk flow) Describe active mechanisms (primary and secondary active transport mechanisms)

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Major Topics
Fluid mosaic model How molecules move across cell membranes Membrane permeability Molecular gradients Transport mechanisms Ions channels Equilibrium potential Osmosis and osmotic pressure Tonicity and osmolarity
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A Generalized Cell
1. Plasma membrane - forms the cells outer boundary - separates the cells internal environment from the outside environment - is a selective barrier - plays a role in cellular communication

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Structure of the Plasma Membrane

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Lipid Bilayer:
barrier to water and water-soluble substances
CO2
ions glucose H2O urea N2 O2

halothane

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Plasma Membrane
Flexible yet sturdy barrier The fluid mosaic model - the arrangement of molecules within the membrane resembles a sea of lipids containing many types of proteins The lipids act as a barrier to certain substances The proteins act as gatekeepers to certain molecules and ions
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Structure of a Membrane
Consists of a lipid bilayer - made up of phospholipids, cholesterol and glycolipids Integral proteins - extend into or through the lipid bilayer Transmembrane proteins - most integral proteins, span the entire lipid bilayer Peripheral proteins - attached to the inner or outer surface of the membrane, do not extend through it
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Functions of Membrane Proteins

Some integral proteins are ion channels Transporters - selectively move substances through the membrane Receptors - for cellular recognition; a ligand is a molecule that binds with a receptor Enzymes - catalyze chemical reactions Others act as cell-identity markers
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Cell Membrane
but, other molecules still get across!
urea ions H2O glucose CO2 N2 O2

halothane

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Permeability coefficients (cm/sec)

(** across an artificial lipid bilayer)
water urea glycerol glucose

10-2 10-4
10-6

high permeability

10-8 10-10 10-12 low permeability

ClK+ Na+

Membrane Permeability
The cell is either permeable or impermeable to certain substances The lipid bilayer is permeable to oxygen, carbon dioxide, water and steroids, but impermeable to glucose Transmembrane proteins act as channels and transporters to assist the entrance of certain substances, for example, glucose and ions

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Molecular Gradients
inside
(in mM)

outside
(in mM)

Na+ K+ Mg2+ Ca2+ H+ HCO3ClSO42PO3protein

14 140 0.5 10-7 (pH 7.2) 10 5-15 2 75 40

142 4 1-2 1-2 (pH 7.4) 28 110 1 4

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Proteins:
provide specificity to a membrane provide function ion channels

carrier proteins

K+
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Diffusion
occurs down a concn. gradient no mediator or involves a channel or carrier no additional energy

Active Transport
occurs against a concn. gradient involves a carrier requires ENERGY

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Passive vs. Active Processes

Passive processes ( downhill) substances move across cell membranes without the input of any energy; use the kinetic energy of individual molecules or ions Active processes (uphill) a cell uses energy, primarily from the breakdown of ATP, to move a substance across the membrane, i.e., against a concentration gradient
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Simple Diffusion
(a) lipid-soluble molecules move readily across the membrane (rate depends on lipid solubility) (b) water-soluble molecules cross via channels or pores (a)

(b)

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Ion Channels
Characteristics:
ungated determined by size, shape, distribution of charge, etc. gated voltage (e.g. voltage-dependent Na+ channels) chemically (e.g. nicotinic ACh receptor channels)
in

Na+

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Na+ and

other

out
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ions

Ion Channels
in

out Na+

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Diffusion is the most important means water, gases, waste products, and solute transfer across the endothelium
Exchange of gases, substances, and waste products between the capillaries and the tissue cells
Quantity of substance moved/time Diffusion coefficient CSA Concentration gradient Capillary permeability

Capillary surface area Concentrations (in and out)

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Diffusion Across a Membrane

Ficks Law of Diffusion:

C J DA X
J= net rate of diffusion in moles or grams per unit time D= diffusion coefficient of the diffusing solute in the membrane which is proportional to S / Mwt. where S= lipid solubilty, Mwt= molecular weight. A= area of the membrane C= concentration difference across the membrane X= thickness of the membrane
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Diffusion of lipid-insoluble molecules is restricted to the pores

Movement of solutes across endothelium is complex and involves: Attractions between solute and solvent Interactions between solute molecules Pore configuration Molecular charge > 60,000 MW do not penetrate the endothelium < 60,000 MW penetrate at a rate inversely proportional to their size
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Lipid-soluble molecules pass directly through the lipid membranes of the endothelium and the pores

Solubility (oil-to-water partition coefficient) provides good index of ease of transfer through endothelium O2 and CO2 readily pass through endothelium Hb is only 80% saturated entering the capillaries (diffusion from arterioles) CO2 loading shifts the oxyhemoglobin dissociation curve in the pre-capillary vessels (countercurrent exchange)
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Simple Diffusion, Channel-mediated Facilitated Diffusion, and Carrier-mediated Facilitated Diffusion

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Channel-mediated Facilitated Diffusion of Potassium ions through a Gated K + Channel

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Extracellular fluid Glucose Glucose transporter

Plasma membrane

Cytosol

Glucose gradient 2

3 Glucose

Carrier-mediated Facilitated Diffusion of Glucose across a Plasma Membrane

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Simple vs. Facilitated

simple diffusion rate of diffusion
Tmax (Vmax)

rate of diffusion (Co-Ci)

facilitated diffusion
Tmax

Km

Concen of substance

What limits maximum rate of facilitated diffusion?

Facilitated Diffusion
(also called carrier mediated diffusion)

Rate of diffusion is limited by Tmax Transport maximum (Vmax -velocity maximum) of the carrier protein the density of carrier proteins in the membrane (i.e., number per unit area) The capacity is determined by Tmax and the affinity is determined by Km
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Factors that affect the net rate of diffusion:

1. Concentration difference (Co-Ci) net diffusion D (Co-Ci)

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Factors Affecting Diffusion

Permeability of the cell membrane Temperature Electrochemical gradient of the substance across the membrane Lipid solubility of the substance Thickness of the cell membrane Size of the molecules M. Wt Size of the ion Charge of the ion
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Net Diffusion

Can a molecule diffuse from side B to side A?

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3. Pressure difference
Higher pressure results in increased energy available to cause net movement from high to low pressure.

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Special types of passive transport

Bulk flow- pressure difference Filtration- hydrostatic pressure gradient Osmosis-water movement

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Osmosis:

- Net diffusion of water -

Osmosis occurs from pure water toward a water/salt solution. Water moves down its concn gradient.

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Osmosis
Net movement of water through a selectively permeable membrane from an area of high concentration of water (lower concentration of solutes) to one of lower concentration of water Water can pass through plasma membrane in 2 ways: 1. through lipid bilayer by simple diffusion 2. through aquaporins, integral membrane proteins

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Tonicity and its effect on RBCS

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Osmotic Pressure:
the amount of pressure required to counter osmosis

Osmotic pressure is attributed to the osmolarity of a solution

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Osmotic Pressure
Vant Hoffs law = RT nC = osmotic pressure mmHg R = ideal gas constant T = absolute temperature in kelvins (273+centigrade degrees) C = concentration of solutes in osmoles per liter n = number of dissociated ions of the substances
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Osmotic Pressure
= Ranges between 1 for none permeable molecules to 0 for freely permeable molecules
Reflection coefficient (relative impediment to passage through capillary wall) Oncotic pressure

Solute (albumin) concentration in and out

Gas constant

Absolute Temperature
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Major determinant of osmotic pressure

A 100 g in 1 L Solute A Mw = 100 B

1000 g in 1L Solute B Mw = 1000

Which solution has the greatest osmolarity? Which has the greatest molar concentration? Which has the greatest number of molecules? (6.02 x 1023 particles)
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Relation between osmolarity and molarity

mOsm (millisomolar) = or mOsm/L
mM (millimolar) or mM/L =

index of the concentration of particles per liter solution

index of concentration of molecules per liter solution

150 mM NaCl = 300 mM glucose =

300 mOsm 300 mOsm

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Estimating Plasma Osmolarity

Plasma is clinically accessible. Dominated by [Na+] and the associated anions Under normal conditions, ECF osmolarity can be roughly estimated as: POSM = 2 [Na+]p mOSM 270-290

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Thank You

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