Cell Membrane Protein Channels
Permeability of Lipid Bilayer to Different Substances
Some ion channels remain open all the time, while many others are opened and closed in response to a signal. Their specificity arises from the structure of the inner part of the channel. The structure of most membrane-spanning proteins is a group of alpha-helices, spiral chains of amino acids stabilized by hydrogen bonds. Residues on the membrane-facing side of the helices have hydrophobic (water-repelling, or having no affinity to water) side chains, while the three-dimensional folding of individual protein molecules that make up the multi-subunit complex allows the channel itself to be hydrophilic (water-attracting). In order to be specific for a particular ion, the inner portion of ion channels also has a selectivity filter, a sequence of amino acids arranged to provide a narrow passageway tailored to one type of ion. For example, in the case of potassium channels, oxygen atoms in the protein mimic the water molecules that surround the ion in solution. This means the selectivity filter can be specific enough to fit the potassium (K+) ion alone, stripped of its usual water molecules. Other ions, unable to have their water molecules removed by this apparatus, are excluded from the channel.Most ion channels are gated, that is, they open only when triggered to do so. A ligand is a molecule that binds to a specific receptor protein to trigger some response. Ligand-gated channels open when they bind a ligand, such as a neurotransmitter. A voltage-gated channel acts as a gate allowing ions into or out of the cell in response to a change in electrical charge across the membrane, as when a nerve or muscle cell is excited. Stress-gated channels open in response to a mechanical stimulus, such as movement or pressure. An ion channel opens when there is a change in the shape of the protein in response to a change in its environment or other factors. When either (1) the ligand dissociates, (2) the electric potential changes (because of the flow of ions through the channel), or (3) the movement or pressure stops, the ion channel closes again.
Selectivity and Gating of Ion Channels
Channel proteins allow ions or molecules to move across the membrane by passive transport. This movement of ions or molecules down their concentration gradient is energetically favorable, so channels do not require additional energy input by the cell to operate. A transmembrane pump, in contrast, uses adenosine triphosphate (ATP) hydrolysis, the breaking down of an ATP molecule into another form through the addition of water, to transport a substrate across the membrane against its concentration gradient. That is, they move their substrates, molecules that are acted upon by an enzyme, across the plasma membrane against their concentration gradient (from a region of lower concentration to a region of higher concentration). Because ions are charged, the gradient is electrochemical, dependent on both the type of ion and its charge. This is a type of active transport because movement against the gradient requires energy, which the transmembrane pump derives from hydrolysis of the molecule ATP. This is called primary active transport, because the pump itself requires energy taken directly from ATP. In contrast, the energy used in secondary active transport comes from the ion pumps that result from primary active transport.
Transmembrane ATPases, enzymes involved in the breakdown of ATP molecules, operate in a variety of ways in cells. The sodium (Na+)/potassium (K+) pump, an ATPase, couples the hydrolysis of ATP to the transfer of sodium (Na+) ions from the interior to the exterior of the cell. In this process, the pump is phosphorylated, meaning that a phosphate group is bound to it, inducing a change in its conformation. The pump can then bind potassium (K+) ions from outside the cell and transport them to the cytoplasm, coupling this process to the dephosphorylation of the pump. Both the Na+ ions and the K+ ions move against their respective concentration gradients. The calcium (Ca2+) ATPase pump, similarly, hydrolyzes ATP in order to pump Ca2+ ions from the cytosol, the aqueous fluid that fills the cytoplasm in the cell, where they exist in low concentration, to the extracellular space or to a special compartment within the cell. These pumps are especially important in muscle cells, where they are involved in stimulating muscle contraction.
While the sodium and calcium pumps are important in animal cells, in plant, fungal, and bacterial cell plasma membranes, it is proton-pumping (H+) ATPase pumps that are responsible for primary active transport. They use ATP hydrolysis to maintain an electrochemical proton gradient across the membrane.
ATP synthase is a transmembrane protein related to the H+ transport ATPases. It is present in the membranes of mitochondria, bacterial cells, and chloroplasts. ATP synthase can operate to move H+ ions across a membrane, utilizing the energy from ATP hydrolysis, but it more often runs in reverse. In this mode, the proton gradient developed by other processes is used to produce ATP for the cell.All cells contain members of a large class of transmembrane proteins called ABC (ATP-binding cassette) transporters. These specialized ATPase transporters operate by a different mechanism that does not involve phosphorylation of the pump. They are often used by cells to transport small molecules. Many are important clinically because the substrates they are able to pump out of cells include drugs used to treat diseases such as cancer and malaria.
Comparison of Primary and Secondary Active Transport
Like transmembrane pumps, cell membrane transport proteins bind to specific substances for transport and undergo a shape change to transport the substrate across the membrane. A transport protein transports a substrate across the membrane, either by facilitated diffusion down the gradient or by cotransport against the gradient of one substrate and down the gradient of the other. Some cell membrane transporters are uniporters and carry out passive transport of a single substrate down its concentration gradient. Others are cotransporters, moving two specific substrates in a coordinated fashion. Cotransporters carry out active transport in one of two ways: symport or antiport. Symport is the cotransport of two substrates by a membrane transport protein in which the substrates cross the membrane in the same direction. Antiport is the cotransport of two substrates by a membrane transport protein in which the substrates cross the membrane in opposite directions.
A carrier protein, which is a protein that physically binds to a molecule and facilitates its transport across the cell membrane's lipid bilayer, is a type of uniporter and provides facilitated diffusion down the concentration gradient of the solute. These proteins are responsible for transporting molecules such as sugars, amino acids, and nucleosides across the plasma membrane. Carrier proteins bind to their specific substrate on the higher-concentration side of the plasma membrane, change their conformation, and then release the molecule on the lower-concentration side. This process is significantly slower than the rate of channel proteins. Both ion channels and carrier proteins are uniporters, because they move a single type of substrate across the plasma membrane by passive transport.The coupled transporters, symporters and antiporters, carry out secondary active transport. A coupled transporter is a transmembrane protein that transports one substrate against its gradient by coupling it to a transport of a second substrate down its gradient. Like transmembrane pumps, they move their substrates across a membrane against the concentration gradient and so require energy. Unlike transmembrane pumps, they do not supply the energy directly through a chemical reaction. Instead, symporters and antiporters use the energy stored in the concentration gradient of one substrate to provide the energy to transport the other substrate. The concentration gradients used by coupled transporters are maintained by the ATPase action of transmembrane pumps.