Nonpolar substances often can diffuse straight through the lipid bilayer without requiring a membrane protein. Examples include oxygen, fatty acids, steroid hormones, and general anesthetics. (Although keep an open mind about possible exceptions here.)
Certain small polar molecules can diffuse through the lipid bilayer. Carbon dioxide and, to a limited extend, water fall in this category.
Ion channels provide actual holes through which the ions can diffuse across the membrane. No binding takes place. A few are open all the time and thus are ungated. Cells tend to have some ungated K+ and ungated Cl- ion channels.
On the other hand, two important ions, Na+ and Ca++, do not have ungated ion channels, but only move through gated ion channels. Much cellular regulation revolves around this point.
Ion channels that open or close in response to changes in the membrane potential are termed voltage-gated. Especially important are voltage-gated Na+, Ca++, K+, and Cl- ion channels, which provide split second regulation in the nervous system and in muscles. The next webpage describes the structure of the voltage-gated Na+ channel in order to provide a specific example of an ion channel.
Many ion channels are ligand-gated; that is, they open in response to the binding of an extracellular or intracellular regulatory molecule.
An important example is the the acetylcholine receptor found in the membrane of skeletal muscle cells. These open in response to neurotransmitter acetylcholine released by the neurons that cause muscle contraction. This ion channel has five subunits, which is a characteristic of an important class of neurotransmitter receptors in the brain. Recall that the acetylcholine receptor is the protein attacked by antibodies in myesthenia gravis.
(An example of an ion channel that opens through the binding of an intracellular ligand is an ion channel for K+ that opens after the binding of ATP from the cytosol. This ion channel plays a role in the secretion of insulin from the pancreas. More on this later in the quarter.)
Examples of ion channels that open in response to mechanical movement of adjacent structures include touch sensors in the skin and vibration sensors in the inner ear that respond to sound. Also, most hollow organs, such as the bladder, intestines and heart, have stretch sensors that respond to expansion of the organ.
Some ion channels are temperature-gated. These are found in sensory neurons in the skin and mucous membranes and open with either an increase in temperature or decrease in temperature. This, of course, leads to the sensations of warm and cold.
Some temperature gated ion channels are interesting because some plants contain molecules that open the ion channels, despite the fact that they are normally temperature-gated rather than ligand-gated channels. The most important is an ion channel that normally opens in response to noxious heat, but that also responds to capsiacin, the substance that gives chili peppers their special characteristic.
QUESTION: Which national cuisine makes the best use of these ion channels? Answer
QUESTION: Can you think of a chemical substance that opens ion channels that normally respond to cooooool stimuli? Answer
Facilitated diffusion is based on transporters that must specifically bind the substance to be transported. The binding causes a conformation change, which allows the transported substance to be released on the other side of the membrane.
In facilitated diffusion, the energy is provided by the concentration gradient of the substance transported. If the concentration of the substance is higher outside the cell than inside, the substance moves inward. Conversely, if the concentration is higher on the inside than on the outside, the substance moves outward. No ATP is required.
Due to the specific binding step, a facilitated transporter can saturate if the concentration of the transported substance becomes high enough. Once this happens, no further increase in the rate of transport can occur, since the binding site on the transporter is occupied essentially all the time. By contrast, this does not occur with ion channels. As the concentration of the ion increases, the amount that moves through the pore of the channel increases proportionately. There is no process that becomes saturated.
The glucose transporter is a widespread and important example of this type of transporter, especially since insulin controls the number of these transporters working in certain cells. When more insulin is present, more of these transporters are added to the membrane of cells such as those in muscle. As a result, more glucose moves into the muscle cells.
The figures shows how this takes place. Insulin leads to exocytosis of vesicles containing glucose transporters . Then, when the insulin concentration in the blood decreases, endocytosis removes some of the glucose transporters and thus less glucose moves into the muscle cells.
In this same way, the number of various transporters or ion channels can change depending on the specific circumstances.
Cotransporters are similar to those in facilitated diffusion in that specific binding takes place and no ATP is expended. It is different in that two substances must bind at the same time before the transport takes place.
The requirement that two substances must be transported together creates a major additional consideration in the energetics. The free energy driving the transport is the sum of the free energys for both substances.
A good example is the cotransporter for glucose and Na+ in the small intestine. Suppose someone eats a donut. The high concentration of glucose in the lumen provides the energy for the transporter to move both Na+ and glucose out of the lumen and into the cell. This transport takes place even if the concentration of Na+ in the lumen is less than in the cell. The Na+ thus moves to a higher concentration, but only provided the free energy required for this is less than that provided by the movement of glucose down its concentration gradient.
Just the opposite happens if the concentration of glucose in the lumen is low and the concentration of Na+ is high. The glucose can move to a higher concentration if the Na+ concentration gradient provides enough energy.
Countertransporters work on similar principles, except the two transported substances move in opposite directions across the membrane.
Active transport is similar to the preceding two mechanism in that specific binding of the transported substance occurs. However, here ATP is required in a step in which the transporter is phosphorylated. Because energy is provided in this way, the transporter can move the substance to a higher concentration. Thus, these transporters always move the transported substance in one direction, regardless of the concentration gradient.
The most widespread active transporter moves three Na+ out of the cell while moving two K+ into the cell. In addition, there are active transporters both for Ca++ and for H+. The later, for example, are found in the stomach and participate in the secretion of acid into stomach.
ABC cassette proteins are an unusual class of proteins that play a number of roles in the body. One example is the CFTR Cl- ion channel found in epithelia lining the intestines and in the airways in the lungs. It opens when it is phosphosphorylated.
In the small intestines, this ion channel opens in response to certain bacterial toxins causing diarrhea. Also, this ion channel is defective in cystic fibrosis, a genetic disorder.
Another example, is the multi-drug resistance transporter (MDR transporter). Using ATP energy, it transports various nonpolar molecules out of the cytosol of cells. It's role is thus to eject various toxic molecules from cells, especially those in the liver, intestines and kidneys.
The cells in liver tumors often express much larger quantities of the MDR transporter than normal. This can make chemotherapy against the tumor cells more difficult than might be expected, since the MDR transporter actively removes the chemotherapy agent from the cell.