Transport Across Cell Membranes


All cells acquire the molecules and ions they need from their surrounding extracellular fluid (ECF). There is an unceasing traffic of molecules and ions

Two problems to be considered:

1. Relative concentrations

Molecules and ions move spontaneously down their concentration gradient (i.e., from a region of higher to a region of lower concentration) by diffusion.

Molecules and ions can be moved against their concentration gradient, but this process, called active transport, requires the expenditure of energy (usually from ATP).

2. Lipid bilayers are impermeable to most essential molecules and ions.

The lipid bilayer is permeable to water molecules and a few other small, uncharged, molecules like
oxygen (O2) and carbon dioxide (CO2). These diffuse freely in and out of the cell. The diffusion of water through the plasma membrane is of such importance to the cell that it is given a special name: osmosis.

Lipid bilayers are not permeable to:

This page will examine how ions and small molecules are transported across cell membranes. The transport of macromolecules through membranes is described in Endocytosis.

Solving these problems

Mechanisms by which cells solve the problem of transporting ions and small molecules across their membranes:
Link to a quantitative treatment of the free energy changes involved in facilitated diffusion and active transport.

Facilitated Diffusion of Ions

Facilitated diffusion of ions takes place through proteins, or assemblies of proteins, embedded in the plasma membrane. These transmembrane proteins form a water-filled channel through which the ion can pass down its concentration gradient.

The transmembrane channels that permit facilitated diffusion can be opened or closed. They are said to be "gated".

Some types of gated ion channels:

Ligand-gated ion channels.

Many ion channels open or close in response to binding a small signaling molecule or "ligand". Some ion channels are gated by extracellular ligands; some by intracellular ligands. In both cases, the ligand is not the substance that is transported when the channel opens.

External ligands

External ligands (shown here in green) bind to a site on the extracellular side of the channel.


Internal ligands

Internal ligands bind to a site on the channel protein exposed to the cytosol.


Mechanically-gated ion channels


Voltage-gated ion channels

In so-called "excitable" cells like neurons and muscle cells, some channels open or close in response to changes in the charge (measured in volts) across the plasma membrane.

Example: As an impulse passes down a neuron, the reduction in the voltage opens sodium channels in the adjacent portion of the membrane. This allows the influx of Na+ into the neuron and thus the continuation of the nerve impulse. [More]

Some 7000 sodium ions pass through each channel during the brief period (about 1 millisecond) that it remains open. This was learned by use of the patch clamp technique.

The Patch Clamp Technique

The properties of ion channels can be studied by means of the patch clamp technique.

Such measurements reveal that each channel is either fully open or fully closed; that is, facilitated diffusion through a single channel is "all-or-none".

This technique has provided so much valuable information about ion channels that its inventors, Erwin Neher and Bert Sakmann, were awarded a Nobel Prize in 1991.

Facilitated Diffusion of Molecules

Some small, hydrophilic organic molecules, like sugars, can pass through cell membranes by facilitated diffusion.

Once again, the process requires transmembrane proteins. In some cases, these — like ion channels — form water-filled pores that enable the molecule to pass in (or out) of the membrane following its concentration gradient.

Example: Maltoporin. This homotrimer in the outer membrane of E. coli forms pores that allow the disaccharide maltose and a few related molecules to diffuse into the cell.

Another example: The plasma membrane of human red blood cells contain transmembrane proteins that permit the diffusion of glucose from the blood into the cell.

Note that in all cases of facilitated diffusion through channels, the channels are selective; that is, the structure of the protein admits only certain types of molecules through.

Whether all cases of facilitated diffusion of small molecules use channels is yet to be proven. Perhaps some molecules are passed through the membrane by a conformational change in the shape of the transmembrane protein when it binds the molecule to be transported.

In either case, the interaction between the molecule being transported and its transporter resembles in many ways the interaction between an enzyme and its substrate. Link to a discussion of the energetics of enzyme-substrate interactions.

Active Transport

Active transport is the pumping of molecules or ions through a membrane against their concentration gradient. It requires:

The energy of ATP may be used directly or indirectly.

Link to a quantitative analysis of these processes.

Direct Active Transport

1. The Na+/K+ ATPase

The cytosol of animal cells contains a concentration of potassium ions (K+) as much as 20 times higher than that in the extracellular fluid. Conversely, the extracellular fluid contains a concentration of sodium ions (Na+) as much as 10 times greater than that within the cell.

These concentration gradients are established by the active transport of both ions. And, in fact, the same transporter, called the Na+/K+ ATPase, does both jobs. It uses the energy from the hydrolysis of ATP to

This accomplishes several vital functions:

The crucial roles of the Na+/K+ ATPase are reflected in the fact that almost one-third of all the energy generated by the mitochondria in animal cells is used just to run this pump.

2. The H+/K+ ATPase

The parietal cells of your stomach use this pump to secrete gastric juice. These cells transport protons (H+) from a concentration of about 4 x 10-8 M within the cell to a concentration of about 0.15 M in the gastric juice (giving it a pH close to 1). Small wonder that parietal cells are stuffed with mitochondria and uses huge amounts of ATP as they carry out this three-million fold concentration of protons.

3. The Ca2+ ATPases

A Ca2+ ATPase is located in the plasma membrane of all eukaryotic cells. It uses the energy provided by one molecule of ATP to pump one Ca2+ ion out of the cell. The activity of these pumps helps to maintain the ~20,000-fold concentration gradient of Ca2+ between the cytosol (~ 100 nM) and the ECF (~ 20 mM). [More]

In resting skeletal muscle, there is a much higher concentration of calcium ions (Ca2+) in the sarcoplasmic reticulum than in the cytosol. Activation of the muscle fiber allows some of this Ca2+ to pass by facilitated diffusion into the cytosol where it triggers contraction. [Link to discussion].

After contraction, this Ca2+ is pumped back into the sarcoplasmic reticulum. This is done by another Ca2+ ATPase that uses the energy from each molecule of ATP to pump 2 Ca2+ ions.

Pumps 1. - 3. are designated P-type ion transporters because they use the same basic mechanism: a conformational change in the proteins as they are reversibly phosphorylated by ATP. And all three pumps can be made to run backward. That is, if the pumped ions are allowed to diffuse back through the membrane complex, ATP can be synthesized from ADP and inorganic phosphate.

4. ABC Transporters

ABC ("ATP-Binding Cassette") transporters are transmembrane proteins that

The ligand-binding domain is usually restricted to a single type of molecule.

The ATP bound to its domain provides the energy to pump the ligand across the membrane.

The human genome contains 48 genes for ABC transporters. Some examples:

ABC transporters must have evolved early in the history of life. The ATP-binding domains in archaea, eubacteria, and eukaryotes all share a homologous structure, the ATP-binding "cassette".

Indirect Active Transport

Indirect active transport uses the downhill flow of an ion to pump some other molecule or ion against its gradient. The driving ion is usually sodium (Na+) with its gradient established by the Na+/K+ ATPase.

Symport Pumps

In this type of indirect active transport, the driving ion (Na+) and the pumped molecule pass through the membrane pump in the same direction.


Antiport Pumps

In antiport pumps, the driving ion (again, usually sodium) diffuses through the pump in one direction providing the energy for the active transport of some other molecule or ion in the opposite direction.

Example: Ca2+ ions are pumped out of cells by sodium-driven antiport pumps [Link].

Antiport pumps in the vacuole of some plants harness the outward facilitated diffusion of protons (themselves pumped into the vacuole by a H+ ATPase)

Some inherited ion-channel diseases

A growing number of human diseases have been discovered to be caused by inherited mutations in genes encoding channels.

Some examples:


Hypotonic solutions

If the concentration of water in the medium surrounding a cell is greater than that of the cytosol, the medium is said to be hypotonic. Water enters the cell by osmosis.

A red blood cell placed in a hypotonic solution (e.g., pure water) bursts immediately ("hemolysis") from the influx of water.

Plant cells and bacterial cells avoid bursting in hypotonic surroundings by their strong cell walls. These allow the buildup of turgor within the cell. When the turgor pressure equals the osmotic pressure, osmosis ceases.

How the kidneys of freshwater fishes and amphibians permit their owners to live in their hypotonic surroundings.

Isotonic solutions

When red blood cells are placed in a 0.9% salt solution, they neither gain nor lose water by osmosis. Such a solution is said to be isotonic.

The extracellular fluid (ECF) of mammalian cells is isotonic to their cytoplasm. This balance must be actively maintained because of the large number of organic molecules dissolved in the cytosol but not present in the ECF. These organic molecules exert an osmotic effect that, if not compensated for, would cause the cell to take in so much water that it would swell and might even burst. This fate is avoided by pumping sodium ions out of the cell with the Na+/K+ ATPase.

Hypertonic solutions

If red cells are placed in sea water (about 3% salt), they lose water by osmosis and the cells shrivel up. Sea water is hypertonic to their cytosol.

Similarly, if a plant tissue is placed in sea water, the cell contents shrink away from the rigid cell wall. This is called plasmolysis. [Link to a view of it.]

Sea water is also hypertonic to the ECF of most marine vertebrates. To avoid fatal dehydration, these animals (e.g., bony fishes like the cod) must

Marine birds, which may pass long periods of time away from fresh water, and sea turtles use a similar device. They, too, drink salt water to take care of their water needs and use metabolic energy to desalt it. In the herring gull, shown here, the salt is extracted by two glands in the head and released (in a very concentrated solution — it is saltier than the blood) to the outside through the nostrils. Marine snakes use a similar desalting mechanism.

How the kidneys of marine fishes are adapted for life in a hypertonic environment.

Osmosis is important!

A report in the 23 April 1998 issue of The New England Journal of Medicine tells of the life-threatening complications that can be caused by an ignorance of osmosis.
  • Large volumes of a solution of 5% human albumin are injected into people undergoing a procedure called plasmapheresis.
  • The albumin is dissolved in physiological saline (0.9% NaCl) and is therefore isotonic to human plasma (the large protein molecules of albumin have only a small osmotic effect).
  • If 5% solutions are unavailable, pharmacists may substitute a proper dilution of a 25% albumin solution. Mixing 1 part of the 25% solution with 4 parts of diluent results in the correct 5% solution of albumin.
  • BUT, in several cases, the diluent used was sterile water, not physiological saline.
  • SO, the resulting solution was strongly hypotonic to human plasma.
  • The Result: massive, life-threatening hemolysis in the patients.

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1 August 2019