Membrane TransportXia Qiang, PhDDepartment of PhysiologyZhejiang University School of MedicineTel: 88206417, 88208252Email: xiaqiang@zju.edu.cn

LEARNING OBJECTIVES

•Describe how solutes cross cell membranes

•Explain how charge, size, and solubility affect solute movement across cell membranes

•Contrast how transporters, pumps & channels work

•Describe how ion channels are gated•Describe how epithelial transport works

Organelles have their own membranes

Cell Membrane (plasma membrane)

Membrane Transport

▫Simple Diffusion（单纯扩散）▫Facilitated Diffusion（易化扩散）▫Active Transport（主动转运）▫Endocytosis and Exocytosis（出胞与入胞）

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)

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

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

Simple diffusion & gap junctions

Facilitated Diffusion

▫Carrier-mediated

Characteristics of carrier-mediated diffusion

net movement always depends on the concentration gradient  

▫Specificity

▫Saturation

▫Competition

– Channel-mediated

3 cartoon models of integral membraneproteins that functionas ion channels; theregulated opening and closing of these channels is the basis of howneurons function.

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（门控）

Three types of passive, non-coupled transport through integral membrane proteins

Voltage-gated Channel

– e.g. Voltage-dependent Na+ channel

Na+ channel

Balloonfish or fugu

Closed Activated Inactivated

Na+ channel conformation– Open-state

– Closed-state

Ligand-gated Channel

– e.g. N2-ACh receptor channel

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.

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Active transport

•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

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

Secondary Active Transport

The ion gradients

established by primary

active transport permits

the transport of other

substances against their

concentration gradients

Cotransport（同向转运）the ion and the second solute cross

the membrane in the same direction

(e.g. Na+-glucose, Na+-amino acid cotransport)

Countertransport（逆向转运）

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

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.

Solvent + Solute = Solution

Osmosis（渗透）

Begin: The partition betweenthe compartmentsis 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 betweenthe compartmentsis permeable to water only.

After diffusional equilibrium has occurred: Movement of water onlyhas equalized solute concentration.

Role of Na-K pump in maintaining cell volume

Response to cell shrinking

Response to cell swelling

Endocytosis and Exocytosis

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

Steps to exocytosis

• Vesicle trafficking: In this first step, the vesicle containing the waste product or chemical transmitter is transported through the cytoplasm towards the part of the cell from which it will be eliminated

• Vesicle tethering: As the vesicle approaches the cell membrane, it is secured and pulled towards the part of the cell from which it will be eliminated

• Vesicle docking: In this step, the vesicle comes in contact with the cell membrane, where it begins to chemical and physically merge with the proteins in the cell membrane

• Vesicle priming: In those cells where chemical transmitters are being released, this step involves the chemical preparations for the last step of exocytosis

• Vesicle fusion: In this last step, the proteins forming the walls of the vesicle merge with the cell membrane and breach, pushing the vesicle contents (waste products or chemical transmitters) out of the cell. This step is the primary mechanism for the increase in size of the cell's plasma membrane

Epithelial Transport（上皮转运）

Measurement of voltage in an epithelium

Models of epithelial solute transport

Mechanisms of intestinal glucose absorption

Models of “isotonic” water transport in a leaky epithelium

Glands

General concepts

Fatty acids enter the cells lining the small intestine by:

A. Simple diffusionB. Facilitated diffusionC. Active transport

The PepT is a H+/peptide antiporter located in the small intestine. It has which of the following characteristics?•A. requires ATP for activity•B. exhibits maximal transport when

saturated•C. requires H+ and peptides for activity•D. B and C•E. A, B, and C