Membrane transport- L1
Faisal I. Mohammed, MD, PhD
Resource: Guyton’s Textbook of Medical Physiology
12th edition.
University of Jordan
1
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)
University of Jordan
2
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
University of Jordan
3
A Generalized Cell
1. Plasma membrane
- forms the cell’s outer boundary
- separates the cell’s internal environment
from the outside environment
- is a selective barrier
- plays a role in cellular communication
University of Jordan
4
Structure of the Plasma Membrane
University of Jordan
5
Lipid Bilayer:
• barrier to water and water-soluble substances
CO2
ions
glucose
H2O
University of Jordan
N2 O2
urea
halothane
6
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
University of Jordan
7
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
University of Jordan
8
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
University of Jordan
9
Cell Membrane
… but, other molecules still get across!
urea
ions H2O
glucose
University of Jordan
CO2
N2 O2
halothane
10
Permeability coefficients (cm/sec)
(** across an artificial lipid bilayer)
water
urea
glycerol
glucose
ClK+
Na+
10-2
high permeability
10-4
10-6
10-8
10-10
10-12
low permeability
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
University of Jordan
12
Molecular Gradients
inside
outside
(in mM)
(in mM)
Na+
K+
Mg2+
Ca2+
H+
HCO3ClSO42PO3-
14
140
0.5
10-7
(pH 7.2)
10
5-15
2
75
protein
40
142
4
1-2
1-2
(pH 7.4)
28
110
1
4
5
Proteins:
• provide “specificity” to a
membrane
• provide “function”
ion channels
carrier proteins
K+
University of Jordan
14
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
University of Jordan
15
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
University of Jordan
16
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)
University of Jordan
17
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+
University of Jordan
Na+ and
ions
other
out
18
Ion Channels
in
out
Na+
University of Jordan
19
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)
University of Jordan
20
Diffusion Across a Membrane
Fick’s 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
University of Jordan
21
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
University of Jordan
22
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)
University of Jordan
23
Simple Diffusion, Channel-mediated Facilitated
Diffusion, and Carrier-mediated Facilitated Diffusion
University of Jordan
24
Channel-mediated Facilitated Diffusion of
Potassium ions through a Gated K + Channel
University of Jordan
25
Extracellular fluid
Glucose
1
Plasma membrane
Cytosol
Glucose
transporter
Glucose
gradient
2
3
Glucose
Carrier-mediated Facilitated Diffusion of
Glucose across a Plasma Membrane
University of Jordan
26
Simple vs. Facilitated
simple diffusion
rate of diffusion  (Co-Ci)
rate of
diffusion
Tmax (Vmax)
facilitated diffusion
½ 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
University of Jordan
28
Factors that affect the net rate of diffusion:
1. Concentration difference (Co-Ci)
net diffusion  D (Co-Ci)
University of Jordan
29
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
University of Jordan
30
Net Diffusion
A
B
Can a molecule diffuse from side B to side A?
University of Jordan
31
3. Pressure difference
• Higher pressure results in increased energy available
to cause net movement from high to low pressure.
University of Jordan
32
Special types of passive transport
 Bulk flow- pressure difference
 Filtration- hydrostatic pressure gradient
 Osmosis-water movement
University of Jordan
33
Osmosis:
- Net diffusion of water -
Osmosis occurs from pure water toward a water/salt solution.
Water moves down its concn gradient.
University of Jordan
34
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
University of Jordan
35
University of Jordan
36
Tonicity and its effect on RBCS
University of Jordan
37
Osmotic Pressure:
the amount of pressure required to counter osmosis
Osmotic pressure is
attributed to the
osmolarity
of a solution
University of Jordan
38
Osmotic Pressure
 Van’t Hoff’s 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
University of Jordan
39
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
Gas constant
Solute (albumin)
concentration in and
out
Absolute
Temperature
University of Jordan
40
Major determinant of osmotic pressure
A
B
100 g
in 1 L
1000 g
in 1L
Solute A
Mw = 100
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)
University of Jordan
41
Relation between osmolarity and molarity
mOsm (millisomolar) =
or mOsm/L
index of the concentration
of particles per liter solution
mM (millimolar)
or mM/L
index of concentration of
molecules per liter solution
=
150 mM NaCl =
300 mOsm
300 mM glucose =
300 mOsm
University of Jordan
42
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
University of Jordan
270-290
43
Thank You
University of Jordan
44