Cross references: Passive Lipid Diffusion Facilitated Diffusion Ion Channels ABC Transporter Transmembrane Transport Evolution Transmembrane Signaling
My summarizing comments. For more detail, see Kimball, below.
There are two ways in which the outside environment and the interior of the cell can influence one another.
1. Transmembrane Transport: The barrier is a differentially permeable and able to regulate what enters and exits the cell, thus facilitating the transport of materials needed for survival. Note that 'transmembrane transport' can be in either direction: from the outside in or from the inside out.
I'm still learning about this, but as far as I can tell at the moment, only some forms of transmembrane transport require receptors.
Passive Diffusion definitely does not require a receptor for substrates to cross the membrane in either direction. However, substrates that pass into the cell by passive diffusion often interact with a receptor inside the cell once they have crossed the membrane interface.
Facilitated Diffusion may or may not require a receptor. I don't yet know one way or the other.
Ion Channels only require receptors when they aren't being gated by the voltage across the cell membrane.
ABC Transporter always require a receptor.
2. Transmembrane Signaling always requires a receptor. Protein receptors are found ubiquitously and function to receive signals from both the environment and other cells. These signals are transduced and passed in a different form into the cell. As far as I know, all 'transmembrane signaling' is from the outside in. The only way the inside of the cell can influence what is outside is via 'transmembrane transport'.
IUPHAR DATABASE OF RECEPTORS AND ION CHANNELS
Transport Across Cell Membranes (Kimball)
extracellular fluid (ECF). There is an unceasing traffic of molecules and ions
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.
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".
External ligands (shown here in green) bind to a site on the extracellular side of the channel.
Internal ligands bind to a site on the channel protein exposed to the cytosol.
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.
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.
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 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.
Direct Active Transport
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
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 ATP as they carry out this three-million fold concentration of protons.
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.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:
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.
In this type of indirect active transport, the driving ion (Na+) and the pumped molecule pass through the membrane pump in the same direction.Examples:
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)
A growing number of human diseases have been discovered to be caused by inherited mutations in genes encoding channels.Some examples:
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.
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.
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.