物质的跨膜转运
MOVEMENT OF MOLECULES
ACROSS CELL MEMBRANES
XIA Qiang, MD & PhD
Department of Physiology
Room 518, Block C, Research Building
School of Medicine, Zijingang Campus
Email: xiaqiang@zju.edu.cn
Tel: 88206417 (Undergraduate school),
88208252 (Medical school)
Outline
Cell structure
Simple diffusion
Facilitated diffusion
Active transport
Endocytosis and exocytosis
Sizes, on a log scale
Electron Micrograph of organelles in a hepatocyte (liver cell)
Organelles have their own membranes
Cell Membrane (plasma membrane)
细胞膜
Phospholipid bilayer
Schematic cartoon of a transmembrane protein
Circles represent amino acids in
the linear sequence of the protein
The amino acids along
the membrane section
are likely to have
non-polar side chains
Structure of cell membrane:
Fluid Mosaic Model (Singer & Nicholson, 1972)
Drawing of the fluid-mosaic model of membranes, showing
the phospholipid bilayer and imbedded proteins
Composition of cell membrane:
Lipids 脂类
Proteins 蛋白质
Carbohydrates 糖类
Lipid Bilayer
Phospholipid
Phosphatidylcholine
Phosphatidylserine
Phosphatidylethanolamine
Phosphatidylinositol
Cholesterol
Sphingolipid
Lipid mobility
Rotation
reducing membrane fluidity
enhancing membrane fluidity
Membrane proteins
Integral
protein
Integral (intrinsic) proteins
Peripheral (extrinsic) proteins
Peripheral
protein
Integral proteins
Functions of
membrane
proteins
Adhesion Some glycoproteins attach to the cytoskeleton and
extracellular matrix.
Carbohydrates
Glycoprotein
Glycolipid
Membrane Transport 跨膜转运
Lipid Bilayer -- primary barrier, selectively permeable
Membrane Transport
Simple Diffusion
Facilitated Diffusion
Active Transport
Primary Active Transport
Secondary Active Transport
Endocytosis and Exocytosis
Importance of pumps, transporters
& channels
Basis of physiologic processes
Growth
Metabolic activities
Sensory perception
Basis of disease
Defective transporters (cystic fibrosis)
Defective channels (long QT syndrome, paralysis)
Basis of pharmacological therapies
Hypertension (diuretics)
Stomach ulcers (proton pump inhibitors)
START: Initially higher
concentration of molecules randomly
move toward lower concentration.
Over time,
solute molecules
placed in a solvent
will evenly distribute
themselves.
Diffusional
equilibrium
is the result
(Part b).
At time B, some glucose has crossed into side
2 as some cross into side 1.
Note: the partition between the two
compartments is a membrane that
allows this solute to move through it.
Net flux accounts for solute
movements in both directions.
Simple Diffusion 单纯扩散
Relative to the concentration
gradient
movement is DOWN the
concentration gradient ONLY
(higher concentration to
lower concentration)
Rate of diffusion depends on
• The concentration gradient
• Charge on the molecule
• Size
• Lipid solubility
• Temperature
Simple diffusion & gap junctions
Facilitated Diffusion 易化扩散
Carrier-mediated diffusion 载体中介的扩散
Channel-mediated diffusion 通道中介的扩散
A cartoon model of carrier-mediated diffusion
The solute acts as a
ligand that binds to
the transporter
protein….
… and then a subsequent
shape change in the
protein releases the
solute on the other side
of the membrane.
In simple diffusion,
flux rate is limited
only by the
concentration
gradient.
In carriermediated
transport,
the number
of available
carriers
places an
upper limit
on the
flux rate.
Characteristics of carrier-mediated diffusion:
net movement always depends on the
concentration gradient
Specificity
Saturation
Competition
– Channel-mediated diffusion
3 cartoon models of
integral membrane
proteins that function
as ion channels; the
regulated opening
and closing of
these channels is
the basis of how
neurons function.
A thin shell of positive (outside) and negative (inside)
charge provides the electrical gradient that drives
ion movement across the membranes of excitable cells.
The opening and closing of ion channels results
from conformational changes in integral proteins.
Discovering the factors that cause these
changes is key to understanding excitable cells.
Characteristics of ion
channels
Specificity
Gating
Three types of passive, non-coupled transport
through integral membrane proteins
Voltage-gated Channel
– e.g. Voltage-dependent Na+ channel
I
II
III
IV
Outside
+
+
+
NH2
+
+
+
+
+
+
+
+
+
CO2H
Inside
Na+ channel
Na+ channel
Balloonfish or fugu
Na+ channel conformation
– Open-state
– Closed-state
Closed
Activated
Inactivated
Ligand-gated Channel
– e.g. N2-ACh receptor channel
Stretch-sensitive Channel
Stretch
Closed
Open
Aquaporin
Aquaporins are water channels that
exclude ions
Aquaporins are found in essentially all
organisms, and have major biological and
medical importance
The Nobel Prize in Chemistry 2003
"for discoveries concerning channels in cell membranes"
"for the discovery of
water channels"
"for structural and
mechanistic studies
of ion channels"
Peter Agre
Roderick MacKinnon
http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2003/popular.html
The dividing wall between the cell and the outside world – including other cells – is far from being
an impervious shell. On the contrary, it is perforated by various channels. Many of these are
specially adapted to one specific ion or molecule and do not permit any other type to pass. Here to
the left we see a water channel and to the right an ion channel.
Peter Agre’s experiment with cells containing or lacking aquaporin. The aquaporin is necessary
for making the cell absorb water and swell
Passage of water
molecules through
the aquaporin
AQP1. Because of
the positive charge
at the center of the
channel, positively
charged ions such
as H3O+, are
deflected. This
prevents proton
leakage through
the channel.
Model for water permeation
through aquaporin
membrane
In both simple and
facilitated diffusion,
solutes move in the
direction predicted
by the concentration
gradient.
In active transport, solutes move opposite to the
direction predicted by the concentration gradient.
Active transport 主动转运
Primary active transport 原发性主动转运
Secondary active transport 继发性主动转运
Primary Active Transport
making direct use of energy derived from ATP to
transport the ions across the cell membrane
The transported solute binds to the protein
as it is phosphorylated (ATP expense).
Concentration gradient of Na+ and K+
Extracelluar (mmol/L)
Intracellular (mmol/L)
Na+
140.0
15.0
K+
4.0
150.0
Here, in the operation of the Na+-K+-ATPase, also known
as the “sodium pump,” each ATP hydrolysis moves three
sodium ions out of, and two potassium ions into, the cell.
Na+-K+ pump (Na+ pump, Na+-K+ ATPase)
electrogenic pump
Physiological role of Na+-K+ pump
–Maintaining the Na+ and K+ gradients across the cell
membrane
–Partly responsible for establishing a negative electrical
potential inside the cell
–Controlling cell volume
–Providing energy for secondary active transport
Other primary active transport
Primary active transport of calcium
Primary active transport of hydrogen ions
etc.
Secondary Active Transport
The ion gradients established by primary active
transport permits the transport of other substances
against their concentration gradients
Secondary active transport uses the energy in
an ion gradient to move a second solute.
Cotransport
the ion and the second solute cross
the membrane in the same
direction
(e.g. Na+-glucose, Na+-amino acid
cotransport)
Countertransport
the ion and the second solute move in
opposite directions
(e.g. Na+-Ca2+, Na+-H+ exchange)
Cotransporters
Exchangers
Ion gradients, channels, and
transporters in a typical cell
Osmosis（渗透）
Solvent + Solute = Solution
Here, water is the solvent. The addition of solute lowers the water
concentration. Addition of more solute would increase the solute
concentration and further reduce the water concentration.
Begin:
The partition between
the compartments
is permeable to water
and to the solute.
After diffusional
equilibrium has occurred:
Movement of water and
solutes has equalized solute
and water concentrations on
both sides of the partition.
Begin:
The partition between
the compartments
is permeable to water only.
After diffusional
equilibrium has occurred:
Movement of water only
has equalized solute
concentration.
Role of Na-K pump in maintaining cell
volume
Response to cell shrinking
Response to cell swelling
Endocytosis and Exocytosis 入胞与出胞
Alternative functions
of endocytosis:
1. Transcellular
transport
2. Endosomal
processing
3. Recycling the
membrane
4. Destroying
engulfed materials
Endocytosis
Exocytosis
Two pathways of exocytosis
•Constitutive exocytosis pathway -- Many soluble proteins are continually
secreted from the cell by the constitutive secretory pathway
•Regulated exocytosis pathway -- Selected proteins in the trans Golgi
network are diverted into secretory vesicles, where the proteins are
concentrated and stored until an extracellular signal stimulates their
secretion
Epithelial Transport
Glands
Summary
Diffusion: solute moves down its concentration gradient:
• simple diffusion:
small (e.g., oxygen, carbon dioxide)
lipid soluble (e.g., steroids)
• facilitated diffusion:
requires transporter (e.g., glucose)
Active transport: solute moves against its concentration gradient:
• primary active transport:
ATP directly consumed (e.g., Na+ -K+ ATPase)
• secondary active transport:
energy of ion gradient (usually Na+) used to move
second solute (e.g., nutrient absorption in gut)
Exo- and endo- cytosis:
large scale movements of molecules
Thank you for your attention!