Transport Across Cell Membranes

Importance

• in and out of the cell through its plasma membrane
  • Examples: glucose, Na⁺, Ca²⁺
• In eukaryotic cells, there is also transport in and out of membrane-bounded intracellular compartments such as the nucleus, endoplasmic reticulum, and mitochondria.
  • Examples: proteins, mRNA, Ca²⁺, ATP

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.

• ions such as
  • K⁺, Na⁺, Ca²⁺ (called cations because when subjected to an electric field they migrate toward the cathode [the negatively-charged electrode])
  • Cl^-, HCO₃^- (called anions because they migrate toward the anode [the positively-charged electrode])
• small hydrophilic molecules like glucose
• macromolecules like proteins and RNA

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

• Facilitated diffusion

  Transmembrane proteins create a water-filled pore through which ions and some small hydrophilic molecules can pass by diffusion. The channels can be opened (or closed) according to the needs of the cell.
  
  

• Active transport

  Transmembrane proteins, called transporters, use the energy of ATP to force ions or small molecules through the membrane against their concentration gradient.

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".

• ligand-gated
• mechanically-gated
• voltage-gated

Ligand-gated ion channels.

External ligands

• Acetylcholine (ACh). The binding of the neurotransmitter acetylcholine at certain synapses opens channels that admit Na⁺ and initiate a nerve impulse or muscle contraction.
• Gamma amino butyric acid (GABA). Binding of GABA at certain synapses - designated GABA_A - in the central nervous system admits Cl^- ions into the cell and inhibits the creation of a nerve impulse.

Internal ligands

• "Second messengers", like cyclic AMP (cAMP) and cyclic GMP (cGMP), regulate channels involved in the initiation of impulses in neurons responding to odors and light respectively.
• ATP is needed to open the chloride (Cl^-) channel allowing Cl^- out of the cell. This channel is defective in patients with cystic fibrosis. Although the energy liberated by the hydrolysis of ATP is needed to open the channel, this is not an example of active transport; the Cl^- ion diffuses through the open channel following its gradient.

Mechanically-gated ion channels

• Sound waves bending the cilia-like projections on the hair cells of the inner ear open up ion channels leading to the creation of nerve impulses that the brain interprets as sound.
• Mechanical deformation of the cells of stretch receptors opens ion channels leading to the creation of nerve impulses.

Voltage-gated ion channels

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. Some 7000 sodium ions pass through each channel during the brief period (about 1 millisecond) that it remains open.

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.

Active Transport

• a transmembrane protein (usually a complex of them) called a transporter and
• energy. The source of this energy is ATP.

The energy of ATP may be used directly or indirectly.

• Direct Active Transport. Some transporters bind ATP directly and use the energy of its hydrolysis to drive active transport.
• Indirect Active Transport. Other transporters use the energy already stored in the gradient of a directly-pumped ion. Direct active transport of the ion establishes a concentration gradient. When this is relieved by facilitated diffusion, the energy released can be harnessed to the pumping of some other ion or molecule.

Direct Active Transport

Example: The Na⁺/K⁺ ATPase

• actively transport 3 Na⁺ ions out of the cell
• for each 2 K⁺ ions pumped into the cell.

• It helps establish a net charge across the plasma membrane with the interior of the cell being negatively charged with respect to the exterior. This resting potential prepares nerve and muscle cells for the propagation of action potentials leading to nerve impulses and muscle contraction.
• The accumulation of sodium ions outside of the cell draws water out of the cell and thus enables it to maintain osmotic balance (otherwise it would swell and burst from the inward diffusion of water).
• The gradient of sodium ions is harnessed to provide the energy to run several types of indirect pumps.

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.

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 energy as they carry out this three-million fold concentration of protons.

Both of these pumps - and probably all direct 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.

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.

• The Na⁺/glucose transporter. This transmembrane protein allows sodium ions and glucose to enter the cell together. The sodium ions flow down their concentration gradient while the glucose molecules are pumped up theirs. Later the sodium is pumped back out of the cell by the Na⁺/K⁺ ATPase.

  The Na⁺/glucose transporter is used to actively transport glucose out of the intestine and also out of the kidney tubules and back into the blood.

• All the amino acids can be actively transported (e.g., out of the kidney tubules and into the blood) by sodium-driven transporters.

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.

Some inherited ion-channel diseases

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

• Chloride-channel diseases
  • Cystic fibrosis
  • inherited tendency to kidney stones (caused by a different kind of chloride channel than the one involved in cystic fibrosis)
• Potassium-channel diseases
  • some inherited life-threatening defects in the heartbeat
  • a rare, inherited tendency to epileptic seizures in the newborn.
• Sodium-channel diseases
  • inherited tendency to certain types of muscle spasms
  • Liddle's syndrome. Inadequate sodium transport out of the kidneys, because of a mutant sodium channel, leads to elevated osmotic pressure of the blood and resulting hypertension (high blood pressure).

Osmosis

• Osmosis is a special term used for the diffusion of water through cell membranes.
• Water passes by diffusion from a region of higher to a region of lower concentration. Note that the key is the concentration of water, NOT the concentration of any solutes present in the water.
• The diffusion of water does not need to be facilitated because cell membranes are freely permeable to water.
• Water is never transported actively; that is, it never moves against its concentration gradient. However, the concentration of water can be altered by the active transport of solutes and in this way the movement of water in and out of the cell can be controlled.

  Example: the reabsorption of water from the kidney tubules back into the blood depends on the water following behind the active transport of Na⁺. [Discussion]

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 build-up of turgor within the cell. When the turgor pressure equals the osmotic pressure, osmosis ceases.

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.

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

• continuously drink sea water and then
• desalt it by pumping ions out of their gills by active transport. (Marine reptiles - turtles and snakes - use special salt glands for the same purpose.)