Human Physiology 人体生理学 Qiang XIA ( 夏强 ), MD & PhD Department of Physiology Room C518,...
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Transcript of Human Physiology 人体生理学 Qiang XIA ( 夏强 ), MD & PhD Department of Physiology Room C518,...
Human Physiology
人体生理学
Qiang XIA (夏强 ), MD & PhDDepartment of PhysiologyRoom C518, Block C, Research Building, School of MedicineTel: 88208252Email: [email protected]
Course Structure
Lectures: 80 academic hours5 a.h./week2 a.h. on Tue., 3 a.h. on Fri.
Practicals: 64 a.h.4 a.h./week
Evaluation
Participation in practicals: 5%Practical reports: 15%Weekly assessments & midterm exam: 30%Final examination: 50%
Recommended textbook
Widmaier EP, Raff H, Strang KT (2006) Vander’s Human Physiology: The Mechanisms of Body Function, Tenth Edition. McGraw-Hill.
Course website
Medical School Course Center: http://10.71.121.158
Course website:http://10.71.121.158/G2S/Template/View.aspx?act
ion=view&courseType=0&courseId=27123
MOVEMENT OF MOLECULES ACROSS CELL MEMBRANES
物质的跨膜转运
Outline
Cell structureSimple diffusionFacilitated diffusionActive transportEndocytosis and exocytosis
Sizes, on a log scale
Ostrich egg
Electron Micrograph of organelles in a hepatocyte (liver cell)
Organelles have their own membranes
Cell Membrane (plasma membrane)细胞膜
Electron micrograph and sketch of plasma membranesurrounding a human red blood cell
Ph
osp
ho
lip
id b
ilay
er
Cir
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s r
ep
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t a
min
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s in
th
e li
nea
r s
equ
en
ce
of
the
pro
tein
Schematic cartoon of a transmembrane protein
Th
e a
min
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cid
s a
lon
g
the
me
mb
ran
e s
ecti
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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
enhancing membrane fluidityreducing membrane fluidity
Rotation
Membrane proteinsIntegral (intrinsic) proteins
Peripheral (extrinsic) proteins
Integral protein Peripheral
protein
Integral proteins
Functions of
membrane
proteins
Adhesion Some glycoproteins attach to the cytoskeleton and extracellular matrix.
CarbohydratesGlycoprotein Glycolipid
Membrane Transport 跨膜转运Lipid Bilayer -- primary barrier, selectively permeable
Simple Diffusion
Facilitated Diffusion
Active Transport
Endocytosis and Exocytosis
Primary Active TransportPrimary Active TransportSecondary Active TransportSecondary Active Transport
Membrane Transport
Over time, solute moleculesplaced in a solventwill evenly distribute themselves.
START: Initially higher concentration of molecules randomly
move toward lower concentration.
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
Facilitated Diffusion 易化扩散
Carrier-mediated diffusion Carrier-mediated diffusion 载体中介的扩散载体中介的扩散
Channel-mediated diffusion Channel-mediated diffusion 通道中介的通道中介的
扩散扩散
The solute acts as a ligand that binds to the transporter protein….
A cartoon model of carrier-mediated diffusion
… 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 carrier-mediated transport, the number of available carriersplaces 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 diffusionChannel-mediated diffusion
3 cartoon models of integral membraneproteins that functionas ion channels; theregulated opening and closing of these channels is the basis of howneurons function.
A thin shell of positive (outside) and negative (inside) charge provides the electrical gradient that drivesion 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
Channel Types:
Voltage-gated Channel
Ligand-gated Channel
Stretch-sensitive Channel
Others
Outside
Inside
NH2CO2H
I II III IV
+++
+++
+++
+++
Voltage-gated ChannelVoltage-gated Channel
– e.g. Voltage-dependent Nae.g. Voltage-dependent Na++ channelchannel
NaNa++ channel channel
NaNa++ channel channel
Balloonfish or fugu
Closed Closed Activated Activated InactivatedInactivated
NaNa++ channel conformation channel conformation– Open-stateOpen-state
– Closed-stateClosed-state
Ligand-gated Channel Ligand-gated Channel
– e.g. Ne.g. N22-ACh receptor channel-ACh receptor channel
Stretch-sensitive ChannelStretch-sensitive Channel
Closed OpenClosed Open
Stretch
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"
Peter Agre Roderick MacKinnon
"for the discovery of water channels"
"for structural and mechanistic studies of ion channels"
http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/public.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
In both simple and facilitated diffusion, solutes move in the direction predicted by the concentration gradient.
In active transport, solutes move opposite to thedirection predicted by the concentration gradient.
mem
bra
ne
Which of the following would decrease the rate of diffusion?a. increasing the size of the diffusing solute
b. increasing the temperature
c. increasing the concentration gradient
d. increasing the surface area for diffusion
e. All of the choices would increase the rate of diffusion
QUIZ
Which of the following would decrease the rate of diffusion?a. increasing the size of the diffusing solute
b. increasing the temperature
c. increasing the concentration gradient
d. increasing the surface area for diffusion
e. All of the choices would increase the rate of diffusion
QUIZ
Carrier- mediated transport
a. involves a specific membrane protein that functions as a carrier molecule.
b. always involves the movement of substances against a concentration gradient.
c. always requires the direct expenditure of energy.
d. Both involves a specific membrane protein that functions as a carrier molecule and always involves the movement of substances against a concentration gradient are correct.
e. All of the choices are correct.
QUIZ
Carrier- mediated transport
a. involves a specific membrane protein that functions as a carrier molecule.
b. always involves the movement of substances against a concentration gradient.
c. always requires the direct expenditure of energy.
d. Both involves a specific membrane protein that functions as a carrier molecule and always involves the movement of substances against a concentration gradient are correct.
e. All of the choices are correct.
QUIZ
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 making direct use of energy derived from
ATP to transport the ions across the cell ATP to transport the ions across the cell
membranemembrane
The transported solute binds to the proteinas 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.
electrogenic pump
NaNa++-K-K++ pump (Na pump (Na++ pump, Na pump, Na++-K-K++ ATPase)ATPase)
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 calciumPrimary active transport of hydrogen ionsetc.
Secondary Active Transport
The ion gradients established by primary active The ion gradients established by primary active
transport permits the transport of other transport permits the transport of other
substances against their concentration gradientssubstances against their concentration gradients
Secondary active transport uses the energy in an ion gradient to move a second solute.
Cotransportthe ion and the second solute cross the
membrane in the same direction(e.g. Na+-glucose, Na+-amino acid
cotransport)
Countertransportthe ion and the second solute move in opposite directions(e.g. Na+-Ca2+, Na+-H+ exchange)
Which of the following statements about the Na,K pump is false?
a. It transports Na+ out of cells and K+ into cells.
b. It binds to and hydrolyzes ATP.
c. It is constantly active in all cells.
d. Its activity requires the expenditure of metabolic energy.
e. It transports Na+ and K+ in a 1:1 ratio.
QUIZ
Which of the following statements about the Na,K pump is false?
a. It transports Na+ out of cells and K+ into cells.
b. It binds to and hydrolyzes ATP.
c. It is constantly active in all cells.
d. Its activity requires the expenditure of metabolic energy.
e. It transports Na+ and K+ in a 1:1 ratio.
QUIZ
If the ATP-generating mechanisms in a cell are poisoned and the cell has depleted its ATP reserves,
a. primary active transport of molecules would cease immediately.
b. secondary active transport of molecules would cease immediately.
c. eventually there will be no potential difference across the membrane.
d. primary active transport of molecules would cease immediately and secondary active transport of molecules would cease immediately are correct.
e. primary active transport of molecules would cease immediately and eventually there will be no potential difference across the membrane are correct.
QUIZ
If the ATP-generating mechanisms in a cell are poisoned and the cell has depleted its ATP reserves,
a. primary active transport of molecules would cease immediately.
b. secondary active transport of molecules would cease immediately.
c. eventually there will be no potential difference across the membrane.
d. primary active transport of molecules would cease immediately and secondary active transport of molecules would cease immediately are correct.
e. primary active transport of molecules would cease immediately and eventually there will be no potential difference across the membrane are correct.
QUIZ
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 movesecond solute (e.g., nutrient absorption in gut)
Exo- and endo- cytosis:
large scale movements of molecules
Thank you for your attention!