Alberts • Bray • Hopkin • Johnson • Lewis • Raff • Roberts • Walter

Essential
Cell Biology
FOURTH EDITION

Chapter 12
Transport Across Cell Membranes

Copyright © Garland Science 2014

The rate at which a molecule diffuses across a synthetic lipid bilayer
depends on its size and solubility
Specialized membrane transport proteins are responsible for transferring small
water-soluble molecules across cell membranes
The Ion Concentrations Inside a Cell Are Very Different from
Those Outside

Electrical imbalances generate a voltage difference across the membrane, called the
membrane potential!
*Resting membrane potential: -20 mV ~ -200 mV
Cells contain two classes of membrane transport
proteins: transporters and channels
Small molecules and ions can enter the cell through a “transporter” or a “channel”

A transporter allows passage Channels discriminate

only to those molecules or ions mainly on the basis of
that fit into a binding site on the size and electric
protein. charge
Small molecules and ions can enter the cell through a “transporter” or a “channel”

A transporter shifts small A channel forms a tiny hydrophilic

molecules from one side of pore in the membrane through which
the membrane to the other solutes, mostly inorganic ions, can
by changing its shape pass by diffusion => ion channel
Most solutes cross cell membranes by passive or active
transport
Both the concentration gradient and membrane potential influence the
passive transport of charged solutes
An electrochemical gradient has two components
Water moves passively across cell membranes down its
concentration gradient – a process called osmosis
Water molecules diffuse rapidly through aquaporin channels in
the plasma membrane of some cells
Cells use different tactics to avoid osmotic swelling
Transporters and their functions
Each cell membrane has its own characteristic set of transporters
Passive transporters move a solute along its
electrochemical gradient

Conformational changes in a transporter mediate the passive

transport of a solute such as glucose
Conformational changes in a transporter mediate the passive
transport of a solute such as glucose

Transporters for passive transport play no role in determining the direction of

transport !
But, they are highly selective (D-glucose vs. L-glucose)
Pumps actively transport a solute against its
electrochemical gradient
The Na+ pump (Na+-K+ ATPase, Na+-K+ pump) uses the energy of
ATP hydrolysis to pump Na+ out of animal cells and K+ in
The Na+ pump generates a steep concentration gradient of Na+
across the plasma membrane
The Na+-K+ Pump transports ions in a cyclic manner
 The Na+-K+ Pump transports ions in a cyclic manner

• Each step in the cycle depends on the one before, so that if any of
individual steps is prevented from occurring, all the functions of the pump
are halted!
• A toxin called Ouabain (plant glycoside) prevents K+ binding
The Na+-K+ Pump helps maintain the osmotic balance of animal
cells
Ca2+ pumps keep the cytosolic Ca2+ concentration low
 Ca2+ pumps keep the cytosolic Ca2+ concentration low

• Ca2+ can bind tightly to a variety of proteins in the cell, altering their activities
(Cal------, calmodulin, calcineurin, protein kinase c (PKC))
• An influx of Ca2+ into the cytosol through Ca2+ channels is often used as a signal to
trigger other cellular events, such as the secretion of signal molecules (nerve cells),
fertilization, and the contraction of muscle cells
• 0.1 M in the cytosol vs. 1~2 mM in the extracellular space : ATP-driven Ca 2+ pumps
in both the PM and the ER
Ca2+ pumps keep the cytosolic Ca2+ concentration low
Ca2+ pumps keep the cytosolic Ca2+ concentration low
Coupled pumps exploit solute gradients to mediate active transport
The electrochemical Na+ gradient drives coupled pumps in the
plasma membrane of animal cells

• Glucose-Na+ symport
Two types of glucose transporters enable gut epithelial cells to transfer
glucose across the epithelial lining of the gut

• Glucose-Na+ symport

• Passive glucose uniport

Electrochemical H+ gradients drive coupled pumps in plants, fungi
(including yeasts), and bacteria
Electrochemical H+ gradients drive coupled pumps in plants, fungi
(including yeasts), and bacteria
ION CHANNELS AND THE MEMBRANE POTENTIAL
Channels form transmembrane aqueous pores that allow the passive
movement of small water-soluble molecules into or out of the cell or
organelle
 Ion channels are ion-selective and gated

• Not a simple hole in the membrane

• Selectivity depends on the diameter and shape of the ion channel and on
the distribution of the charged amino acids
 Ion channels are ion-selective and gated

• Gated: ion channels open briefly and then close again upon a specific
stimulus
A typical ion channel fluctuates between closed and open
conformations
A K+ channel possesses a selectivity filter that controls which ion it
will transport across the membrane

(partially negative charge)

 Transport rate?

A typical ion channel transfers ions 1000 times faster than the
fastest transporter !
Membrane potential is governed by the permeability of a
membrane to specific ions
 The distribution of ions on either side of a cell membrane gives
rise to its membrane potential
(electrical charge difference across the membrane)

(1) In an animal cell that is in a unstimulated, or “resting”, state, the negative

charges on the organic molecules inside the cell are largely balanced by K +

(2) K+ is actively imported into the cell by the Na+ pump, which generates a K +
gradient across the plasma membrane (PM).
(3) The PM contains a set of K+ channels known as K+ leak channels. These
channels randomly flicker between open and closed states no matter what the
conditions are inside or outside the cell
(4) When they are open, they allow K+ to move freely.
(5) In a resting cell, these are the main ion channels open in the PM, rending the
PM much more permeable to K+ than to other ions.
The distribution of ions on either side of a cell membrane
gives rise to its membrane potential
The K+ concentration gradient and K+ leak channels play major
parts in generating the resting membrane potential across the PM
in animal cells
Resting Membrane Potential

-The membrane potential is such steady-state conditions, where the

flow of positive and negative ions across the plasma membrane is
precisely balanced, so that no further difference in charge
accumulates across the membrane

-In animal cells, the resting membrane potential varies between -20
and -200 millivolts (mV), depending on the organism and cell type.

-Nernst equation: each ten-fold change in the ion concentration ration

(Co/Ci) alters the membrane potential by 62 milli-volts
How is ion-channel activity measured?
Patch-clamp recording
Patch-clamp recording is used to monitor ion
channel activity
A nerve cell held in a suction pipette, while a microelectrode is being
used for patch-clamp recording
The circuitry for patch-clamp recording
The behavior of a single ion channel can be observed
using the patch-clamp technique
This graph shows a recording from a patch-clamp experiment in which the
electrical current passing across a patch of membrane is measured as a function of
time. The membrane patch was plucked from the PM of a muscle cell by the
technique mentioned earlier and contains molecules of the acetylcholine receptor,
which is a ligand-gated cation channel that is opened by the binding of
acetylcholine.
Different Types of Stimuli Influence the Opening and Closing of
Ion Channels

The probability of being open is controlled by

Membrane Ligand Mechanical

potential binding force
Stress-gated ion channels allow us to hear !
Tilting stretches the filaments, which pull open stress-gated ion
channels in the stereocillium membrane
Voltage-gated Ion Channels Respond to the Membrane Potential

Voltage-gated channels have

specialized charged protein
domains called “voltage sensors”
that are extremely sensitive to
changes in the membrane potential
Voltage-gated Ion Channels Respond to the Membrane Potential

What controls the membrane potential?

Voltage-gated Ion Channels Respond to the Membrane Potential

What controls the membrane potential?

Ion channels!

Ion channels → membrane potential →

ION CHANNELS AND NERVE CELL SIGNALING
A typical neuron has a cell body, a single axon, and multiple
dendrites
The axon conducts signals away from the cell body towards its
target cells, while the multiple dendrites receive signals from
the axons of other neurons
Thousands of synapses form on the cell body and dendrites
of a motor neuron in the spinal cord
Action Potentials (nerve impulses) Provide for Rapid
Long-Distance Communication

100 m/s
Action potentials are usually mediated by voltage-gated Na+
channels

An action potential is triggered by a depolarization of a neuron’s

plasma membrane
 Action potentials are usually mediated by voltage-gated Na+
channels

Around +40mV, the electrochemical driving force for Na+ movement is zero: the
effects of the membrane potential and the concentration gradient for Na + are equal
and opposite!
A voltage-gated Na+ channel can flip from one conformation to
another, depending on the membrane potential
Voltage-gated Na+ channels change their
conformation during an action potential
During an action potential, voltage-gated Na+ channels
do not act alone!

Voltage-gated K+ channels & K+ leak channels

An action potential can be propagated along the length of
an axon
The changes in the Na+ channels and the consequent flows of
electrical across the membrane give rise to the traveling action
potential
Voltage-gated Ca2+ channels in nerve terminals convert an
electrical signal into a chemical signal
Neurons connect to their target cells at synapses
An electrical signal is converted into a secreted chemical
signal at a nerve terminal
A chemical signal is converted into an electrical signal by post-
synaptic transmitter-gated ion channels at a synapse
The acetylcholine receptor in the PM of vertebrate skeletal muscle
cells opens when it binds the neurotransmitter acetylcholine
Neurotransmitters can be excitatory or inhibitory

• Excitatory neurotransmitters stimulate the post-synaptic cells,

encouraging it to fire an action potential
• Acetylcholine and glutamate receptors are ligand-gated cation
(Na+, Ca2+) channels
• Inhibitory neurotransmitters discourage the postsynaptic cells
from firing
• -aminobutyric acid (GABA) and glycine receptors are
ligand-gated Cl- channels
Neurotransmitters can be excitatory or inhibitory
Most psychoactive drugs affect synaptic signaling by binding
to neurotransmitter receptors

The complexity of synaptic signaling enables us to think, act,

learn and remember
Light-gated ion channels can control the activity of specific
neurons in a living animal
Light-gated ion channels can control the activity of specific
neurons in a living animal

Opto-genetics!