Chapter 12
Membrane Transport
Definitions
• Solution – mixture of dissolved molecules in a liquid
• Solute – the substance that is dissolved
• Solvent – the liquid
Membrane Transport Proteins
• Many molecules must move back and forth from inside
and outside of the cell
• Most cannot pass through without the assistance of
proteins in the membrane bilayer
– Private passageways for select substances
• Each cell has membrane has a specific set of proteins
depending on the cell
Movement of Small Molecules
Ion Concentrations
• The maintenance of solutes on both sides of the
membrane is critical to the cell
– Helps to keep the cell from rupturing
• Concentration of ions on either side varies widely
– Na+ and Cl- are higher outside the cell
– K+ is higher inside the cell
– Must balance the the number of positive and negative
charges, both inside and outside cell
Impermeable Membranes
• Ions and hydrophilic
molecules cannot easily pass
thru the hydrophobic
membrane
• Small and hydrophobic
molecules can
• Must know the list to the left
2 Major Classes
• Carrier proteins – move the solute across the membrane
by binding it on one side and transporting it to the other
side
– Requires a conformation change
• Channel protein – small hydrophilic pores that allow for
solutes to pass through
– Use diffusion to move across
– Also called ion channels when only ions moving
Proteins
Carrier vs Channel
• Channels, if open, will let solutes pass if they have the
right size and charge
– Trapdoor-like
• Carriers require that the solute fit in the binding site
– Turnstile-like
– Why carriers are specific like an enzyme and its
substrate
Mechanisms of Transport
• Provided that there is a pathway, molecules move from a
higher to lower concentration
– Doesn’t require energy
– Passive transport or facilitated diffusion
• Movement against a concentration gradient requires
energy (low to high)
– Active transport
– Requires the harnessing of some energy source by the
carrier protein
• Special types of carriers
Passive vs Active Transport
Carrier Proteins
• Required for almost all small organic molecules
– Exception – fat-soluble molecules and small uncharged
molecules that can pass by simple diffusion
• Usually only carry one type of molecule
• Carriers can also be in other membranes of the cell
such as the mitochondria
Carriers in the Cell
Passive Transport by Glucose Carrier
• Glucose carrier consists of a protein chain that crosses the
membrane about 12 times and has at least 2 conformations
– switch back and forth
• One conformation exposes the binding site to the outside of
the cell and the other to the inside of the cell
How it Works
• Glucose is high outside the cell so the conformation is open
to take in glucose and move it to the cytosol where the
concentration is low
• When glucose levels are low in the blood, glucagon
(hormone) triggers the breakdown of glycogen (e.g., from
the liver), glucose levels are high in the cell and then the
conformation moves the glucose out of the cell to the blood
stream
• Glucose moves according to the concentration gradient
across the membrane
• Can move only D-glucose, not mirror image L-glucose
Calcium Pumps
• Moves Ca2+ back into the sarcoplasmic reticulum (modified
ER) in skeletal muscle
Voltage Across the Membrane
• Charged molecules have another component – a voltage
across the membrane = membrane potential
• Cytoplasm is usually negative relative to the outside, pulls in
positive charges and move out negative charges
• Movement across membrane is under 2 forces –
electrochemical gradient
– Concentration gradient
– Voltage across the membrane
Electrochemical Gradient
• This gradient determines the direction of the solute during
passive transport
Active Transport
• 3 main methods to move solutes against an
electrochemical gradient
– Coupled transporters – 1 goes down gradient and 1 goes up the
gradient
– ATP-driven pumps – coupled to ATP hydrolysis
– Light-driven pumps – uses light as energy, bacteriorhodopsin
Transporters are Linked
• The active transport proteins are linked together so that
you can establish the electrochemical gradient
• Example
– ATP-driven pump removes Na+ to the outside of the cell
(against the gradient) and then re-enters the cell through
the Na+-coupled transporter which can bring in many
other solutes
– Also seen in bacterial cells to move H+
Na+-K+ ATPase (Na+-K+ Pump)
• Requires ATP hydrolysis to maintain the Na+-K+
equilibrium in the cell
• Transporter is also a ATPase (enzyme)
• This pump keeps the [Na+] 10 to 30 times lower than
extracellular levels and the [K+] 10 to 30 times higher
than extracellular levels
Na+-K+ Pump
• Moves K+ while moving Na+
• Works constantly to maintain [Na+] inside the cell –
Na+ comes in thru other channels or carriers
Na+ and K+ Concentrations
• The [Na+] outside the cell stores a large amount of energy,
like water behind a dam
– Even if the Na+-K+ pump is halted, there is enough
stored energy to conduct other Na+ downhill reactions
• The [K+] inside the cell does not have the same potential
energy
– Electric force pulling K+ into the cell is almost the same
as that pushing it out of the cell
Na+-K+ Pump is a Cycle
Na+-K+ Mechanisms
• Pump adds a PO4+ group so that it can pick up 3 Na+
• When 3 Na+ are in place, change shape and pump Na+ out
• Opens site for 2 K+ to bind, when in place, PO4+ group is
removed and it changes to original shape
• Dumps K+ to inside, reforming the site for 3 more Na+
• Visit http://highered.mcgrawhill.com/sites/0072437316/student_view0/chapter6/animations.html
– See animation at Sodium-Potassium Exchange Pump (682.0K)
Coupled Transporters
• The energy in the Na+-K+ pump can be used to move a second
solute
– Energy trapped in the Na+ gradient to move down its gradient
and another molecule against its gradient
• Couple the movement of 2 molecules in several ways
– Symport – move both in the same direction
– Antiport – move in opposite direction
• Carrier proteins that only carry one molecule is called uniport (not
coupled)
•
Visit http://highered.mcgrawhill.com/sites/0072437316/student_view0/chapter6/animations.html
– See animation at Cotransport
Coupled Transporters
Na+-Driven Symport
• If one molecule of the transport pair is missing, the
transport of the second does not occur
2 Methods of Glucose Transport
• 2 mechanisms are separate
– Passive transport at the
apical surface
– Active transport at the basal
surface
• Caused by the tight junctions
Na+-Driven Transport
• Na+ driven symport
– Used to move other sugars and amino acids
• Na+ driven antiport
– Also very important in cells
– Na+-H+ exchanger is used to move Na+ into the cell
and then moves the H+ out of the cell
• Regulates the pH of the cytosol
Osmosis
• The movement of water from region of low solute
concentration (high water concentration) to an area of
high solute concentration (low water concentration)
• Driving force is the osmotic pressure caused by the
difference in water pressure
Osmotic Solutions – Tonicity
(tonos = tension)
• Isotonic – equal solute on each side of the membrane
• Hypotonic – less solute outside cell, water rushes into cell and
cell bursts
• Hypertonic – more solute outside cell, water rushes out of cell
and cell shrivels
Osmotic Swelling
• Animal cells maintain normal cell structure with Na+-K+ pump
(moves out Na+ and prevents Cl- from moving in)
• Plants have cell walls – turgor pressure is the effect of osmosis
and active transport of ions into the cell – keeps leaves and
stems upright
• Protozoans have special water collecting vacuoles to remove
excess water
Human Red Blood Cells or Erythrocytes
Tonicity in Action
• An isotonic solution has an
equal amount of dissolved
solute in it compared to
the things around it.
• Typically in humans and
most other mammals, the
isotonic solution is 0.9
weight percent (9 g/L) salt
in aqueous solution, this is
also known as saline, which
is generally administered
via an intra-venous drip.
• Red blood cells normally
exist in a 0.9 percent salt
solution (saline) with the
same concentration of salt
in the outside solution.
•
Source: http://en.wikipedia.org/wiki/Isotonic.
Water, water, everwhere…
•
•
•
“Water, water, everywhere,
Nor any drop to drink” (pt. II,
st. 9. from the “The Rhyme of
Ancient Mariner ” by Samuel
Taylor Coleridge [1772-1834])
Seawater is water from a sea
or ocean. On average,
seawater in the world's
oceans has a salinity of ~3.5%.
This means that for every 1
liter of seawater there are 35
grams of salts (mostly, but not
entirely, sodium chloride)
dissolved in it. Source:
http://en.wikipedia.org/wiki/Sea_water
A person who drinks undiluted sea
water will actually become more
dehydrated & may salt in the
intestine may cause diarrhea. To
could potentially extend your
drinking supply though; it can be
diluted with potable water by a
factor of 4 or greater to bring it
below a concentration of 0.9%
solute, rendering it safer for
consumption.
Calcium Pumps
• Calcium is kept at low concentration in the cell by ATPdriven calcium pump similar to Na+-K+ pump with the
exception that it does not transport a second solute
• Tightly regulated as it can influence many other molecules
in the cytoplasm
• Influx of calcium is usually the trigger of cell signaling
H+ Gradients
• Drive the movement of molecule across the membranes
of plants, fungi and bacteria
• Similar to animal Na+-K+ pump but moves H+
H+ Pumps
Several reasons for moving H+
through membranes in plants
• Cell wall acidification (H+) helps to loosen the
cellulose fibers so that plant cells can increase in
size and elongate.
• Cation ion exchange by means of secreting H+
allows roots to harvest positively charged mineral
nutrients (e.g., Mg++, Ca++, K+, Na+) that are
attached to negatively charged clay particles in
the soil.
• The relative concentrations of H+ in vacuoles
varies. With anthocyanins (a natural pH indicator)
in the cell sap of a vacuole, this imparts the color
seen in some flowers and other plant tissues (e.g.
hydrangea, violets, ornamental maize, purple
cabbage).
Loosening of cell wall through cell
wall acidification in plants
CATION EXHANGE IN PLANTS
Anthocyanins, pH, and color in plants
Channel Proteins
• Channel proteins create a hydrophilic opening in which
small water-soluble molecules can pass into or out of the
cell
– Gap junctions and porins make very large openings
• Ion channels are very specific with regards to pore size
and the charge on the molecule to be moved
– Move mainly Na, K, Cl and Ca
Ion Channels
• Have ion selectivity – allows some ions to pass and
restricts others
– Based on pore size and the charges on the inner ‘wall’ of
the channel
• Ion channels are not always open
– Have the ability to regulate the movement of ions so that
control can maintain the ion concentrations within the cell
– Channels are gated – open or closed
• Specific stimuli triggers the change in shape and
opening or closing of channel
Ion Channels
Channels Are Either Open or Closed
Membrane Potential
• Basis of all electrical activity in cells
• Active transport can keep ion concentration far from
equilibrium in the cell
• Channels open and the ions rush in because of the
gradient difference – changes the voltage across the
membrane
– As voltage changes, other ion channels open and other
ions rush in
• Allows for the electrical activity to move across the
membrane
Variety of Channels
• Ion channels vary with respect to
– Ion selectivity – which ions can go thru
– Gating – conditions that influence opening and closing
Membrane Ion Channels
Types of plasma membrane ion channels
Passive, or leakage, channels – always open
Chemically (or ligand)-gated channels – open
with binding of a specific neurotransmitter (the
ligand)
Voltage-gated channels – open and close in
response to changes in the membrane potential
Mechanically-gated channels – open and close in
response to physical deformation of receptors
3 Types of Channels
• Voltage-gated channels – controlled by membrane potential
• Ligand-gated channels – controlled by binding of a ligand to a
membrane protein (either on the outside or the inside)
• Stress activated channel – controlled by mechanical force on the
cell
Auditory Hair Cells
• Stress activated
• Sound waves cause the stereocilia to tilt and this causes the
channels to open and transport signal to the brain
• Hair cells to auditory nerve to brain
Voltage-Gated Channels
• Move impulses along the nerve
• Have voltage sensors that are sensitive to changes in
membrane potential
– Allows for changes in the charge across the membrane
• Distribution of ions gives rise to membrane potential
– Usually negative inside and positive outside
END OF THIS
PRESENTATION
THE REMAINING SLIDES
PROVIDE ADDITIONAL
INFORMATION – FYI FOR
WHICH THE FINAL EXAM
WILL NOT COVER
Voltage-Gated Channel
•Example: Na+ channel
•Closed when the intracellular environment is negative
•Open when the intracellular environment is positive Na+ can enter the cell
Ligand-Gated Channel
Example: Na+-K+ gated channel
Closed when a neurotransmitter is not bound to the
extracellular receptor
Open when a neurotransmitter is attached to the receptor Na+ enters the cell and K+ exits the cell
Resting Membrane Potential
A potential (-70mV) exists across the membrane of
a resting neuron – the membrane is polarized
Resting Membrane Potential
• inside is negative relative to
the outside
• polarized membrane
• due to distribution of ions
• Na+/K+ pump
Resting Membrane Potential
Ionic differences are the consequence of:
•Different membrane permeabilities due to passive
ion channels for Na+, K+, and Cl•Operation of the sodium-potassium pump
Membrane Potentials: Signals
Neurons use changes in membrane potential to
receive, integrate, and send information
Membrane potential changes are produced by:
•Changes in membrane permeability to ions
•Alterations of ion concentrations across the membrane
Two types of signals are produced by a change in
membrane potential:
•graded potentials (short-distance)
•action potentials (long-distance)
Levels of Polarization
•Depolarization – inside of the membrane becomes
less negative (or even reverses) – a reduction in
potential
•Repolarization – the membrane returns to its
resting membrane potential
•Hyperpolarization – inside of the membrane
becomes more negative than the resting potential –
an increase in potential
Depolarization increases the probability of producing
nerve impulses. Hyperpolarization reduces the
probability of producing nerve impulses.
Changes in Membrane Potential
Graded Potentials
Short-lived, local changes in membrane potential
(either depolarizations or hyperpolarizations)
Cause currents that decreases in magnitude with
distance
Their magnitude varies directly with the strength of
the stimulus – the stronger the stimulus the more the
voltage changes and the farther the current goes
Sufficiently strong graded potentials can initiate
action potentials
Graded Potentials
Voltage changes in graded
potentials are decremental,
the charge is quickly lost
through the permeable
plasma membrane
short- distance signal
Action Potentials (APs)
An action potential in the axon of a neuron is called a
nerve impulse and is the way neurons communicate.
The AP is a brief reversal of membrane potential with
a total amplitude of 100 mV (from -70mV to +30mV)
APs do not decrease in strength with distance
The depolarization phase is followed by a
repolarization phase and often a short period of
hyperpolarization
Events of AP generation and transmission are the
same for skeletal muscle cells and neurons
Action Potential: Resting State
Na+ and K+ channels are closed
Each Na+ channel has two voltage-regulated gates
Activation gates –
closed in the resting
state
Inactivation gates –
open in the resting
state
Depolarization opens the activation gate (rapid)
and closes the inactivation gate (slower) The gate
for the K+ is slowly opened with depolarization.
Depolarization Phase
Na+ activation gates open quickly and Na+ enters
causing local depolarization which opens more
activation gates and cell interior becomes
progressively less negative. Rapid depolarization and
polarity reversal.
Threshold – a critical level of depolarization
(-55 to -50 mV) where
depolarization becomes
self-generating
Positive Feedback?
Repolarization Phase
Positive intracellular charge opposes further Na+ entry.
Sodium inactivation gates of Na+ channels close.
As sodium gates close, the slow voltage-sensitive K+
gates open and K+ leaves the cell following its
electrochemical gradient and the internal negativity of
the neuron is restored
Hyperpolarization
The slow K+ gates remain open longer than is needed
to restore the resting state. This excessive efflux causes
hyperpolarization of the membrane
The neuron is
insensitive to
stimulus and
depolarization
during this time
Role of the SodiumPotassium Pump
Repolarization restores the resting electrical
conditions of the neuron, but does not restore the
resting ionic conditions
Ionic redistribution is accomplished by the
sodium-potassium pump following repolarization
Potential Changes
• at rest
membrane is
polarized
• threshold
stimulus reached
• sodium
channels open
and membrane
depolarizes
• potassium leaves
cytoplasm and
membrane
repolarizes
Phases of the Action Potential
Impulse Conduction
Action Potentials
Propagation of an Action
Potential
The action potential is self-propagating and
moves away from the stimulus (point of
origin)
Threshold and Action Potentials
Threshold Voltage– membrane is depolarized by 15
to 20 mV
Subthreshold stimuli produce subthreshold
depolarizations and are not translated into APs
Stronger threshold stimuli produce depolarizing
currents that are translated into action potentials
All-or-None phenomenon – action potentials
either happen completely, or not at all
Stimulus Strength and AP
Frequency
Absolute Refractory Period
When a section of membrane is generating an AP and
Na+ channels are open, the neuron cannot respond to
another stimulus
The absolute refractory period is the time from
the opening of the Na+ activation gates until the
closing of inactivation gates
Relative Refractory Period
The relative refractory period is the interval
following the absolute refractory period when:
Na+ gates are closed
K+ gates are open
Repolarization is occurring
During this period, the threshold level is elevated,
allowing only strong stimuli to generate an AP
(a strong stimulus can cause more frequent AP
generation)
Refractory Periods
Synapse
A junction that mediates information transfer from
one neuron to another neuron or to an effector cell
Presynaptic neuron – conducts impulses toward
the synapse (sender)
Postsynaptic neuron – transmits impulses away
from the synapse (receiver)
Chemical Synapses
Specialized for the release and reception of chemical
neurotransmitters
Typically composed of two parts:
Axon terminal of the
presynaptic neuron containing
membrane-bound synaptic
vesicles
Receptor region on the
dendrite(s) or soma of the
postsynaptic neuron
Synaptic Cleft
Fluid-filled space separating the presynaptic and
postsynaptic neurons, prevents nerve impulses from
directly passing from one neuron to the next
Transmission across the synaptic cleft:
Is a chemical event (as opposed to an electrical
one)
Ensures unidirectional communication between
neurons
Synaptic Cleft: Information
Transfer
Nerve impulses reach the axon terminal of the
presynaptic neuron and open Ca2+ channels
Neurotransmitter is released into the synaptic cleft via
exocytosis
Neurotransmitter crosses the synaptic cleft and binds
to receptors on the postsynaptic neuron
Postsynaptic membrane permeability changes due to
opening of ion channels, causing an excitatory or
inhibitory effect
Synaptic Cleft: Information
Transfer
Termination of Neurotransmitter Effects
Neurotransmitter bound to a postsynaptic neuron
produces a continuous postsynaptic effect and also
blocks reception of additional “messages”
Terminating Mechanisms:
Degradation by enzymes
Uptake by astrocytes or the presynaptic
terminals
Diffusion away from the synaptic cleft
Synaptic Delay
Neurotransmitter must be released, diffuse across
the synapse, and bind to receptors (0.3-5.0 ms)
Synaptic delay is the rate-limiting step of neural
transmission
Postsynaptic Potentials
Neurotransmitter receptors mediate graded changes
in membrane potential according to:
The amount of neurotransmitter released
The amount of time the neurotransmitter is
bound to receptors
Inhibitory Postsynaptic
Potentials
Neurotransmitter binding to a receptor at inhibitory
synapses reduces a postsynaptic neuron’s ability to
generate an action potential
Postsynaptic membrane is hyperpolarized due to
increased permeability to K+ and/or Cl- ions. Na+
permeability is not affected.
Leaves the charge on the inner membrane face
more negative and the neuron becomes less likely
to “fire”.
EPSPs and IPSPs
Neurotransmitters
Chemicals used for neuron communication with
the body and the brain
More than 50 different neurotransmitters have
been identified
Classified chemically and functionally
Neurotransmitters
Neurotransmitters – Chemical
classification
•Acetylcholine (ACh)
•Biogenic amines
•Amino acids
•Peptides
•Novel messengers: ATP and dissolved gases
NO and CO
Neurotransmitters:
Acetylcholine
Released at the neuromuscular junction
• Enclosed in synaptic vesicles
• Degraded by the acetylcholinesterase (AChE)
Released by:
– All neurons that stimulate skeletal muscle
– Some neurons in the autonomic nervous
system
Functional Classification of
Neurotransmitters
Two classifications: excitatory and inhibitory
– Excitatory neurotransmitters cause depolarizations
(e.g., glutamate)
– Inhibitory neurotransmitters cause hyperpolarizations
(e.g., GABA and glycine)
Some neurotransmitters have both excitatory and
inhibitory effects (determined by the receptor type of
the postsynaptic neuron). ACh is excitatory at
neuromuscular junctions with skeletal muscle and
Inhibitory in cardiac muscle.
Divergence
• one neuron sends
impulses to several
neurons
• can amplify an
impulse
• impulse from a
single neuron in
CNS may be
amplified to
activate enough
motor units
needed for muscle
contraction
Convergence
• neuron receives input from
several neurons
• incoming impulses represent
information from different
types of sensory receptors
• allows nervous system to
collect, process, and respond
to information
• makes it possible for a
neuron to sum impulses from
different sources
Animations on ion flow and signaling
in neurons and muscles
• http://highered.mcgrawhill.com/sites/0072437316/student_
view0/chapter45/animations.html#