Membrane channels and pumps
Stryer ch 13
Concentration & potential differences across cell membranes
MEMBRANE TRANSPORT SYSTEMS
Regulate the cellular volume
Control the transfer of metabolites across membranes
Maintain ionic and molecular gradients across membranes
DIFFERENT TYPES OF TRANSPORT SYSTEMS
Passive diffusion e.g, hydrophobic molecules
Facilitated diffusion by channels e.g. transfer of
metabolites and ions
Active transport
The thermodynamics of transport across membranes
!’’, c’’
!’, c’
µ’’
µ’
µ’ = µ0 + RT ln c’ + zF!’
µ’’ = µ0 + RT ln c’’ + zF!’’
"G = µ’’ - µ’ = RT ln c’’/c’ + zF (!’’ - !’)
"G > 0 active transport
"G < 0 passive transport
Outside cell
Inside cell
[Na+]
140 mM
10 mM
[K+]
5 mM
100 mM
"G = RT ln c’’/c’ + zF "!
Transport of 3 mol Na+ from inside to outside of a cell at a
transmembrane potential of 70 mV
"G = 3 RT ln [Na+]out / [Na+]in + 3 F (!out - !in)
= (20.5 + 20.5) kJ = 41 kJ
Transport of 2 mol K+ from outside to inside of a cell
"G = 2 RT ln [K+]in / [K+]out + 2 F (!in - !out)
= (15.5 - 13.5) kJ = 2 kJ
At physiological conditions ATP
ADP + P
"G = -60 kJ
Conditions required for a protein to work as a
transmembrane pump
• Protein must contain binding sites to fix substances
which should be transported
• Protein must exist in two conformations
• Binding sites must have different affinities in the two
conformations
Free energy changes for transport processes
"G = RT ln c’’/c’ + zF "!
Structure of the Ca2+ ATPase
The transport mechanism of the Ca2+ ATPase
The transport mechanism of the Ca2+ ATPase
The transport mechanism
of the Na+- K+ ATPase
[Na+]
Outside cell
Inside cell
140 mM
10 mM
[K+]
5 mM
100 mM
Some co-transport systems
Molecule
transported
Ion gradient
Organism
or tissue
Glucose
Na+
Intestine, kidney
Amino acids
Na+
Mouse tumor cells
Lactose
H+
E. coli
Scheme of active transport by Lactose Permease
Scheme of active transport by Lactose Permease
X-ray structure of Lactose Permease
Structural changes of Lactose Permease during active transport
Ion Channels
Morphology of two types of mammalian neurons
Transport rate of ions across membranes
Pumps
ca 1000 ions/second
Channels
106 - 107 ions/second
Some properties of ion channels
1. Ion channels can be highly selective
2. They exist in an open and a closed state
3. The transition between open / closed stae is regulated
4. Open states often spontaneously convert to inactivated form
Schematic representation of a synapse
Voltage-gated ion channels
Ligand-gated ion channels
Synaptic vesicles: 104 Ach
300 vesicles release Ach
[Ach] 10 nM > 500 µM in ms
Ach binds to postsynaptic
membrane
Membrane depolarization
Patch clamp technology
E Neher & B Sakmann 1976
Patch clamp recording of acetylcholine receptor channel
Electrical eel: source of AchR
Torpedo Marmorata
+
Action potentials are mediated by transient changes of Na+
and K+ permeabilities
Opening of
AchR channel
Opening of K+ channels &
restoration of resting potential
Topology of Na+ channel
Sequence relationships of ion channels
Structure of potassium channel
Details of structure of
potassium channel
Considerations on the
energy of ion selectivity
Summary
Specific channels rapidly transport ions across membranes
Ions flow down their concentration gradient
Responsible for nerve impulses
- Specificity for certain ions
- Existence of open & closed states
- Regulated by ligands or trans-membrane potential