Ch 5: Membrane Dynamics
Cell membrane structures and functions
– Mass balance and homeostasis
– Diffusion
– Protein-mediated transport
– Vesicular transport
– Transepithelial transport
– Osmosis and tonicity
– (The resting membrane potential)
Mass Balance
• Law of mass balance applies to human
body
• 2 options for output:
Fig 5-2
– Excretion
– Metabolism (production of metabolites)
• Liver is major organ for clearance
• Other ways to clear molecules: Kidneys,
saliva, sweat, breast milk, hair, lungs
Homeostasis
• Body’s ability to maintain relatively stable
internal environment (dynamic steady
state!)
• H2O is in osmotic equilibrium (free movement)
• Yet: selective permeability of cell
membrane leads to chemical and electrical
disequilibrium between ECF and ICF
• Whole body is electrically neutral
Transport Across Cell Membrane
Cell membrane is selectively permeable
Permeability is variable
Relevant properties of membrane
- Availability of transport proteins
- Cholesterol content
Relevant properties of molecule
- Size and
- Charge (lipid solubility)
Passive vs. active transport
Properties of Diffusion
Passive – based on inherent Ekin of all molecules
In open system or across partitions
Net movement down chemical / conc. gradient
until state of equilibrium reached
Direct correlation to temperature (why?)
Indirect correlation to molecule size
Slower with increasing distance
Distance – Time Relationship
Time for diffusion to progress to given distance ~ to
distance squared
diffusion over 100 m takes 5 sec.
diffusion over 200 m takes ??
diffusion over 400 m takes ??
diffusion over 800 m takes ??
Diffusion effective only over short distances!
Simple Diffusion
• Movement of lipophilic molecules
directly through phospholipid bilayer.
E.g.?
• Diffusion rate 
1
Thickness of membrane
• Diffusion rate  to membrane surface
area
Fig 5-6
Fick’s law of Diffusion
Diffusion
rate

surface x conc.
area
gradient
X
membrane
permeability
membrane thickness
Protein Mediated Transport
For all lipophobic molecules
Two mediated transport categories:
1. Passive transport (facilitated diffusion)
2. Active transport
Two categories of transporter proteins
1. Channel proteins (rapid but not very selective – for
small molecules only)
2. Carrier proteins (slower but very selective – also for
large molecules)
Three other functions of membrane proteins
Fig 5-7
Channel Proteins
• For small molecules e.g.?
• Aquaporins
• > 100 ion channels
• Selectivity based on
diameter and
________________
• All have “gate” region
Fig 5-10
Open Channels vs. Gated Channels
= pores
Gates closed most of the
time
Have gates, but gates
are open most of
the time.
Chemically gated
channels (controlled by
Also referred to as
“leak channels”.
Voltage gated
channels (controlled by
messenger molecule or
ligand)
electrical state of cell)
Mechanically gated
channels (controlled by
physical state of cell:
temp.; stretching of cell
membrane etc.)
Carrier Proteins (2nd type of transport protein)
Compare to Fig 5-13
• Never form direct
connection between ECF
and ICF
• Bind molecules and change
conformation
• Used for small organic
molecules (such as?)
• Ions may use channels or
carriers
• Rel. slow (1,000 to 1 Mio /
sec)
Uniport vs. Cotransport
Symport
Molecules are
carried in same
direction
Examples:
Glucose
and Na+
Antiport
Molecules are
carried in opposite
direction
Examples:
Na+/K+
pump
Facilitated Diffusion
Form of carrier mediated, passive
transport
Some characteristics same as simple
diffusion
but also:
• specificity
• competition
• saturation
More later
Fig 5-14
Summary: Passive Transport
= Diffusion (Def?) – 3 types:
1. Simple diffusion
2. Osmosis
3. Facilitated diffusion (= mediated transport)
Active Transport
•
•
•
•
Movement from low to high conc.
ATP needed
Creates state of ____ equilibrium
Primary (direct) active transport
– ATPases or “pumps” (uniport and antiport)–
examples?
• Secondary (indirect) active transport
– Symport or antiport
1o Active Transport
• ATP energy directly fuels transport
• Most important example: Na+/K+ pump =
sodium-potassium ATPase (uses up to 30% of
cell’s ATP)
• Establishes Na+
conc. gradient 
Epot. can be
harnessed for
other cell functions
Fig 5-17
ICF: high [K+],
low [Na+]
ECF: high
[Na+], low [K+]
Fig 5-16
Secondary Active Transport
• Indirect ATP use: uses Epot. stored in
conc. gradient
• Coupling of Ekin of one molecule with
movement of another molecule
• Example: Na+ / Glucose symporter
Fig 5-18
other examples
• 2 mechanisms for Glucose transport
Specificity, Competition, and Saturation
characterize Carrier-Mediated
Transport
• Specificity (e.g.: GLUT transporters for
hexoses)
• Competition (competitive inhibition
applied in medicine, e.g.: gout)
• Saturation (numbers of carriers can be
adjusted)
Vesicular Transport
Movement of large molecules
across cell membrane:
1. Phagocytosis
2. Endocytosis
– Pinocytosis
– Receptor mediated endocytosis
– Potocytosis
3. Exocytosis
Phagocytosis
• Requires energy
• Cell engulfs particle into vesicle via
pseudopodia formation
• E.g.: some WBCs engulf bacteria
• Vesicles formed are much larger than
those formed by endocytosis
• Phagosome fuses with lysosomes  ? (see
Fig. 5-23)
Endocytosis
•
•
•
•
Requires energy
No pseudopodia - Membrane surface indents
Smaller vesicles
Nonselective: Pinocytosis for fluids & dissolved
substances
• Selective:
– Receptor Mediated Endocytosis via clathrin-coated
pits - Example: LDL cholesterol and Familial
Hypercholesterolemia
– Potocytosis via caveolae
Fig 5-24
Exocytosis
Intracellular vesicle fuses with membrane 
Requires energy and Ca2+
Examples: goblet cells, fibroblasts; receptor
insertion; waste removal
Movement through Epithelia:
Transepithelial Transport
Uses combination of active and passive transport
Molecule must
cross two
phospholipid
bilayers
Polarity of epithelial cells → Apical and basolateral
cell membrane has different proteins:
Na+- glucose transporter on apical membrane
Na+/K+-ATPase only on basolateral membrane
Fig 5-26
Transcytosis
• Endocytosis  vesicular transport 
exocytosis
• Moves large proteins intact
• Examples:
– Absorption of maternal
antibodies from
breast milk
– Movement of proteins
across capillary
endothelium
Osmosis
Compare to Fig. 5-29
Movement of water down its concentration
gradient.
Opposes
movement
Osmotic of water
pressure across
membrane
Water moves freely in body until osmotic
equilibrium is reached
Molarity vs. Osmolarity
In chemistry:
• Mole / L
• Avogadro’s # / L
In Physiology
Important is not # of
molecules / L but
# of particles / L:
osmol/L or OsM
Why?
Osmolarity takes into account the
dissociation of molecules in solution
Convert Molarity to Osmolarity
Osmolarity = # of particles / L of solution
• 1 M glucose = ? OsM glucose
• 1 M NaCl = ? OsM NaCl
• 1 M MgCl2 = ? OsM MgCl2
• Osmolarity of human body ~ 300 mOsM
• Isosmotic, hyperosmotic, hyposmotic
Tonicity
• Physiological term describing volume
change of cell if placed in a solution
• Always comparative. Has no units.
– Isotonic
– Hypertonic
– Hypotonic
• Depends not just on osmolarity (conc.) but
also on nature of solutes (penetrating vs.
nonpenetrating solutes)
Penetrating vs. Nonpenetrating Solutes
• Penetrating solute: can enter cell
(glucose, urea)
• Nonpenetrating solutes: cannot
enter/leave cell (sucrose, NaCl*)
• Determine relative conc. of
nonpenetrating solutes in solution and in
cell to determine tonicity.
– Water will move to dilute nonpenetrating solutes
– Penetrating solutes will distribute to equilibrium
Fig 5-31
IV Fluid Therapy
2 different purposes:
– Get fluid into dehydrated cells or
– Keep fluid in extra-cellular compartment
Resting Membrane Potential
IC and EC compartments are in electrical
disequilibrium
Review basics of electricity if necessary
K+ is major intracellular cation
Na + is major extracellular cation
Water = conductor / cell membrane =
Electro-Chemical Gradients
• Allowed for by cell membrane
• Created via
–Active transport
–Selective membrane permeability to
certain ions and molecule
Fig 5-32
• Membrane potential = unequal distribution
of charges across cell membrane
Resting Membrane Potential Difference
• All cells have it
• Resting  cell at rest (all cells)
• Membrane Potential  separation of charges
creates potential energy
• Difference  difference between electrical
charge inside and outside of cell (ECF by
convention 0 mV)
• Measuring membrane potential differences
Fig 5-33
Resting Membrane Potential Mostly Due to
Potassium
Cell membrane
– impermeable to Na+, Cl - & Pr –
– permeable to K+
 K+ moves down concentration gradient (from
__________ to ____________ of cell)
 Excess of neg. charges inside cell
 Electrical gradient created
Neg. charges inside cell attract K+ back into cell
Equilibrium Potential for K+
Eion= Membrane potential difference
at which movement down
concentration gradient equals
movement down electrical gradient
In other words: At Eion: electrical gradient
equal to and opposite concentration
gradient
EK+ = - 90 mV
Fig 5-34
Equilibrium Potential for Na+
• Assume artificial cell with membrane
permeable only to Na+
• Redistribution of Na+ until movement
down concentration gradient is
exactly opposed by movement down
electrical gradient
ENa+ = + 60 mV
Fig 5-35
Resting Membrane Potential
In most cells between -50 and 90 mV (average ~ -70 mV)
Reasons:
• Membrane permeability:
> Na+ at rest
• Small amount of Na+ leaks into cell
• Na+/K+-ATPase pumps out 3 Na+ for 2 K+
pumped into cell
K+
Changes in Ion Permeability
• lead to change in membrane potential
• Terminology:
Stimulus
Depolarization
Repolarization
Hyperpolarization
Fig 5-37
Explain
• Increase in membrane potential
• Decrease in membrane potential
• What happens if cell becomes more
permeable to potassium
• Maximum resting membrane potential
a cell can have
Insulin Secretion
• Membrane potential changes play
important role also in non-excitable
tissues!
• -cells in pancreas have two special
channels:
– Voltage-gated Ca2+ channel
– ATP-gated K+ channel
Fig 5-38
Cells Avoid Reaching Glucose
Equilibrium
???
Running problem:
Cystic Fibrosis