Membrane transport
Chemistry 256
Types of ion channels (passive transport)
• Mechanosensitive channels – touch, sound, osmotic
pressure changes
• Ligand-gated channels – external chemical signal
(neurotransmitter)
• Signal-gated channels – internal chemical signal (Ca2+)
• Voltage-gated channels – membrane potential changes,
The neuron’s action potential
• A nerve impulse works as a
coordinated effort between
a Na+ channel former and a
K+ channel former. There is
a high [Na+] and a low [K+]
outside the cell membrane.
• As the neural membrane is
stimulated, the Na+ channel
opens, allowing Na+ to flow
into the cell, and causing
nearby Na+ channels to
open, which propagates the
signal.
Changes in neuron membrane ion permeability
• This depolarizes
(reduces) the
membrane potential,
which causes nearby
K+ channels to open,
allowing K+ to flow out
of the cell, which
repolarizes (increases)
the membrane
potential.
• But both gates close
soon after the
repolarization, and it
takes a little while to
bring the membrane
back to a resting
potential by the work
of other ion pumps.
Mechanism of opening/closing a K+ channel
• The S’s in the diagram below represent α-helices; S4 is the site
of the “voltage sensor” and S5 and S6 are the site of the K+
channel itself.
• As S4 builds up potential, the S4-S5 “linker” helix shifts, allow
S6 to shift, opening the channel.
Different ions, different channel mechanisms
• K+ channels work by physically opening or closing the
channel (the position of the helix, the position of the
N-terminus “ball”)
• Cl– channels work by repulsion or lack of repulsion of
the ion by a Glu.
K+ channel
Aquaporins
• Though most cell membranes allow water to pass
freely due to its small size and high concentration,
some cells have such high water throughput that
they need help.
Aquaporins (Agre, 1992) allow high rate
of water transport but are quite
selective; H3O+ cannot pass through. The
protein has a constriction in the center
that allows one water molecule at a time
to pass through and severs the “proton
wire.”
Transport proteins use different
conformations to perform transport
• Well, we knew this from hemoglobin (RT).
Gap junctions allow fast intercellular
communication
• Gap junctions are a bundle of
similar proteins called
connexins.
• The space in the center of the
bundle is hollow and allows
small molecules and ions to
pass from cell to cell without
going “outside”.
• Some organs, like the heart,
are topologically continuous
because the cells are all
connected by these junctions.
How to tell mediated (protein-assisted) from
nonmediated (simple diffusion) transport
• The diffusion
equation is linear in
concentration; that is,
flux  [solute]
• So simple diffusion
should yield a line in
a [solute] vs. flux plot
• If it doesn’t, then it is
mediated transport
Transport proteins can move one or
more substrate molecules
• Uniport = movement of one molecule at a time
(GLUT 1, for instance)
• Symport = movement of two different molecules
in the same direction at the same time (lactose
permease carries H+ and lactose into a bacterial
cell, using the H+ gradient to move lactose against
its gradient (secondary active transport))
• Antiport = movement of two different molecules
in opposite directions at the same time
(oxalate/formate transporter)
Active transport – mostly coupled to the free
energy of ATP hydrolysis to move substrates
•
•
•
•
•
P-type ATPase; P = phosphorylation; cation transporters
F-type ATPase; F = Fn-subunits; proton transporters
V-type ATPase; V= vacuolar; proton transporters
A-type ATPase; A = anion; anion transporters
ABC transporters; ABC = ATP-binding cassette; multiple
substrate transporters
Na+-K+ ATPase (pump) antiport
• For each ATP, it pumps 3 Na+ into cell and pumps 2 K+ out of
cell. Critical to remove Na+ to prevent cytolysis. 70% of nerve
cells’ ATP goes to this protein.
• Note that a net charge separation will occur.
Two conformations of Na+-K+ pump
• A particular aspartate residue can be
phosphorylated only in the presence of Na+,
whereas hydrolysis of the phosphorylated
aspartate occurs only in the presence of K+.
• Thus, two states.
Active and passive transport work in tandem
• Na+-glucose transport system in intestinal epithelial cells
concentrates glucose in the cell
• Glucose is in low concentration in the intestinal lumen, but is
driven into the cell by the Na+ gradient, which is maintained
by the Na+-K+ ATPase