Download Membrane Transport

Stephen Fish, Ph.D.
Marshall University J. C. E. School of Medicine
[email protected]
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Stephen E. Fish, Ph.D.
Membrane Transport:
Carriers & Channels
The membrane lipid barrier:
Passive diffusion through the lipid bilayer
•
•
•
•
Concentration gradient up, diffusion up
Molecule lipid solubility up, diffusion up
Molecular size up, diffusion down
Molecule electrically charged, diffusion blocked
Specialized membrane proteins transport
molecules across membranes
• Simple diffusion
– Species of molecule limited
by membrane physics
– Rate is slow and linearly
related to concentration
gradient
• Membrane transport
– Overall not limited by size,
charge, or hydrophilia
– Is highly selective for
specific needed molecules
– Rate is fast and not linear
Membrane protein transporter types
Channels facilitate diffusion
through an aqueous pore
when a conformational
change opens a gate
Some carrier types facilitate
diffusion, others use energy
to pump molecules against
Their gradient. They must
bind the solute to initiate
a conformational change
Carrier types
• Uniporter- transports only one molecule species
• Symporter- coupled transport of 2 different
molecular species in the same direction
• Antiporter- coupled transport of 2 different
molecular species in the opposite direction
• Symporters & antiporters are usually pumps
• Some types transport more than one molecule of a
species/cycle
The glucose uniporter transports glucose
across membranes
• Ligand (glucose) binding flips the transporter to a
different conformation (changes shape)
• The new conformation releases glucose on the
other side of the membrane
• Release allows it to flip back to repeat the cycle
How carrier proteins change conformation
The ligand binding
site is exposed on
the upper membrane
surface
The folding pattern flips to a different
position
The ligand binding
site is now exposed on
the lower membrane
surface
Without the ligand bound, conformation
returns to the first state
The carrier is
now ready to
transport another
molecule
Band 3 facilitated diffusion anion
antiporter in red blood cells
• Multipass protein that binds to spectrin
• Exchanges Cl- for HCO3• Important for transporting CO2 to the lungs
Band 3 facilitated diffusion anion
antiporter in red blood cells
• When the bicarbonate diffusion gradient is
reversed, the process reverses
Band 3 function in RBCs
Why HCO3- for CO2?
Why antiport Cl-?
Primary active transport example:
The Na+- K+ antiporter pump
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•
•
•
Pumps 3 Na+ ions out of cell & 2 K+ ions in
Maintains Na+ & K+ cell membrane gradients
Each cycle uses one ATP, 100 cycles/sec
Uses ¼ energy of most cells, ¾ for neurons
The Na+ - K+ pump cycle
The Na+- K+ ATPase pump is responsible for
maintaining cellular osmotic balance
Charged intracellular
molecules attract ions
& increase internal tonicity
The pump’s net
effect is to
remove + ions
If the pump is blocked by ouabain
More water
enters
Secondary active transport example:
The sodium-glucose symporter pump
• Gradients from primary pumps power secondary
active transport
• Different types, can be antiporters or symporters
• Pictured, the Na+ gradient powers conformational
change
• Glucose is pumped in against its gradient
Retrieval of GI tract glucose by enterocytes
Channels are selective for ion species
• Some are very
specific, others less
• Specificity based on
– Size
– Charge
• Special problem for K+
channels
– Na+ is smaller & same
charge
– Requires a special filter
I
K+ channel
blocks Na+
II
K+ channel
blocks Na+
Most channel transporters are gated
• Opening & closing of the
gate mechanism
–
–
–
–
Ligand gated
Voltage gated
Mechanically gated
Other types later in the
course
• A few are not gated =
leak channels
Leak channels
• Open all the time
• Best known type are K+
channels
• K+ going down
concentration gradient
out of the cell
• Increases inside
negativity of the cell
• Gradient created by the
Na+-K+ pump
Ligand gated channels
• Binding of ligand changes conformation of
the channel
• Gate opens to allow an ion (+ or -) to enter or
exit the cell
The K+ leak channel charges
up the membrane
• The K+- Na+ pump charges up
concentration gradients
• Excess + ions out accounts
for only a small portion of the
-60mv membrane potential
• The leak channel lets more +
ions out
• The electrical potential rises
until it equals & balances the
K+ concentration gradient =
no more leak
Hormones can trigger
secretion
• Example- Pancreatic cells
secrete digestive enzymes
into the small intestine
• The cell is charged up by the
leak channel
• Ligand opens gate on Ca++
channel
• Membrane potential & Ca++
gradient sum
• Ca++ entering triggers fusion
of vesicles with membrane
Voltage gated channels
• Are sensitive to voltage
across the cell
membrane
• When the voltage
changes to a trigger
level, it opens
• The gate will close again
when the voltage returns
to the trigger level
• What is the problem with
this picture?
Many channels are inactivated by a
separate mechanism than the gate
• The voltage gated Na+ channel serves as a
good example
• Opening the channel depolarizes the cell & if
it stayed open the gate would never close
• The inactivating mechanism provides for a
short positive pulse of current into the cell
Mechanically gated channels:
hair cells in the ear
Sherman says
Actually, I like to
eat them
proteins