Introduction:

Cell membranes are not permeable to all molecules. Small molecules like oxygen and carbon dioxide diffuse rapidly across membranes. Small uncharged polar molecules like water or urea diffuse more slowly (but large uncharged polar molecules like glucose can not readily diffuse). In contrast, lipid bilayers are highly impermeable to charged molecules (ions) due to their charge and high degree of hydration. For these ions, special transport proteins are required.

The process by which a carrier protein transfers a solute molecule across the lipid bilayer resembles an enzyme-substrate reaction in that when the carrier is saturated (all solute binding sites are occupied), the rate of transport is maximal (Vmax).

There are different types of transmembrane transport (also called “carrier-mediated transport”):

Facilitated or Passive Diffusion: 

Passive Transport: Many substances can move in and out of the cell without the cell’s having to expend energy. This type of movement is temred “passive transport”. Some ions and molecuels can pass thorugh the membrane failry easily and do so because of a concentraiton gradient inside the membrane versus outside.

Facilitated or “passive” diffusion: In the case of an uncharged molecule, this mechanism simply uses the concentration gradient or the difference in concentration on the two sides of a membrane. If the solute carries a net charge, both its concentration gradient and the electrical potential difference across the membrane which when combined constitutes theelectrochemical gradient for the solute.

–Facilitated diffusion of ions through channels: (see also ion channels):

Some substances also move in resonse to a concentration gradient, but do so through specific protein channels in the membrane. Channel proteins have a hydrophilic interior that provides an aqueous channel through which polar molecuels can pass when the channel is open. (carrier proteins on the other hand, bind specifically to the molecule they assist).

–Facilitated Diffusion by Carrier Proteins:

Carriar proteins:bind specifically to a molecule that they assit, much like an enzyme binds to the substrate. Thus in contrast to ion channels, carrier proteins bind specifically to the molecule they assist. Carriers must bind to teh molecule they transport, so as concetnration increases, more of the carriers are bound to the transported molecule until all carriers are occupate wehre hte rate of trnasport will be constant.

Vetebrate red blood cells (RBCs) provide an example of facilitated diffusion. One RBC carreir protein transprot a different molecule in each direction: chloride ion (Cl-) in one direction and bicarbonate ion (HCO3-) in the opposite direction. This carrier is also important in the uptake and rlease of carbon dioxide.

Glucose is also transported in RBCs by facilitated diffusion through a sepcifi carrier protein. When glucose binds to the transporter, this alters the shape of the carrier, pulling glucose through the bilayer and releasing it inside the plasma mebrane. Releasing glucose causes the transporter to revert to its orginal shape so it can bind another glucose molecule outside the cell.

Osmosis:

Osmosis is the movement of water across membranes.

Water molecuels interact with dissolved solutes by forming hydration shells around the cahrged solute molecuels. The concetnration of cell solutes in a solution determines the osmotic concentraiton of the solution. If two solutions have unqueal osmotic concentraitons, the solution with the higher concentration is hypertonic and the solution with lower concetnraiton is hypotonic. A plasma membrane separates two solutions; the cytoplams and the extracellualr fluid. The direction and extent of any diffusion of water across the plasma membrane is determined by comparing the osmotic strenght of these solutions. Water diffuses out of a cell in a hypertonic solution (where the cytoplasm of the cell is hypotonic compared with the extracellular fluid). Thes loss of water causes the cell to shrink until the osmotic concentraiton of the cytoplasm and the extrcellular fluid become equal.

In a hypotonic solution (the cell’s cytoplasm is hypertonic relative to the extracellular fluid), water diffuses into the cell causing the cell to swell. As water enters the cell form a hypotonic solution, pressue is applied to the plasma membrane until it bursts. It is important for animal cells, which only ahve a plasma mebrane, to maintain osmotic balance. Blood contains a high concetnraiton of the protein albumin which elevates the solute concetnraiton of the blood to match that of one’s cell’s cytoplasm. Cells of prokaryotes, fungi, plants and many protists are surrounded by strong cell walls, which can withstand high internal pressures without bursting.

Aquaporins: Water channels:

Studies on artifical membranes show that water, despite its polarity, can cross the membrane, but this flow is limited. Water flow in living cells is faciltiated by aquoporins which are specialized channels for water. More than 11 different kinds of aquaporins have been found in mammals. Tehse fall into two classes; those that are specific for only water and those that allow other small hydrophilic molecules, such as glycerol or urea, to cross the membrane as well. The human genetic disease hereditary (nephrogenic) diabetes insipidus (NDI) has been shown to be caused by a nonfunctional aquaporin protein. This diesase causes the excretion of large olumes of dilute urine.

Active transport: 

Active transportrequires a source of metabolic energy such as ATP.

Na+/K+ ATPase:

A prime example of such active transport is the Na+/K+ ATPase which moves 3 Na+ out of the cell and 2 K+ into the cell. Since this pump drives 3 positively charged ions out and 2 in, it tends to create an electrical potential with the cell’s inside negative relative to the outside (the pump, however, does not contribute more than 10% to the membrane potential).

One model for how this pump works is that binding of Na+ and the subsequent phosphorylation by ATP of the cytoplasmic face of the pump induces the protein to undergo a conformational change that transfers Na+ across the membrane and releases it on the outside where K+ then binds and the subsequent dephosphorylation returns the protein to its original conformation which transfers K+ across the membrane and into the cytosol.

Although this pump contributes no more than 10% to the membrane potential of the cell, it is extremely important in regulating osmolarity of the cell. Cells contain a high concentration of solutes like negatively charged organic molecules on the inside of the cell and their accompanying cations which creates a large osmotic gradient. This effect is counteracted by an opposite osmotic gradient due to a high concentration of inorganic ions, mainly Na+ and Cl- in the extracellular fluid. The Na+/K+ maintains this balance by pumping out Na+ that leaks in down its steep electrochemical gradient. Cl- is kept out by the membrane potential of the cell.

Ca2+ ATPase:

Another transport ATPase is the Ca2+ ATPase which moves  Ca2+ from the cytosol back into the sarcoplasmiic reticulum after an action potential depolarizes a muscle cell and releases Ca2+ from the SR. This is important for muscle contraction. Muscles are stimulated to contract by motor neurons. When a somatic motor neuron delivers electrochemical impuses, it stimulates contraction of the muscle fibers; it innervates (makes synapses with) through the following steps: (1) the motor neuron, at the neuromuscular junction, releases the neurotransmitter acetylcholine (ACh). ACh binds to receptors in the muscle cell membrane to 0pen Na+ channels. The influx of Na+ ions depolarizes the muscle cell membrane. (2) the impulses spread along the membrane of the muscle fiber and are carried into the muscle fibers through T tubules. (3) the T tubules conduct the impulses toward the sarcoplasmic reticulum, opening Ca2+ channels and releasing Ca2+. The Ca2+ binds to troponin, exposing the myosin-binding sites on the actin myofilaments and stimulating muscle contraction. (4) When the motor neuron stops sending electrical impulses, it also ceases releasing ACh, in turn stopping the production of impulses in the muscle fiber. Another membrane protein in the SR then uses energy from ATP hydrolysis to pump Ca2+ back into the SR by active transport. Tropinin is no longer bound to Ca2+, so tropomyosin returns to its inhibitory position, allowing the muscle to relax. When a muslce is relaxed, its mysin heads are in the activated conformation bound to ADP and Pi, but they are unable to bind to actin. In the relaxed state, the attachment site for the myosin heads on the actin are physically blocked by tropomyosin, in the thin filaments. Cross-bridges therefore cannot form and the filaments cannot slide. For contraction to occur, the tropomyosin must be moved out of the way so that the myosin heads can bind to the uncovered actin-binding sites. This requires the aciton of troponin, a regulatory protein complex that holds tropomyosin and actin together. The regulatory interactions between troponin and tropomyosin are controled by the Ca2+ concentraiton of the muscle fiber. When the ca2+ cocentraiton of the cytoplams is low, tropomyosin inhibts cross-bridge formation. When the Ca2+ rises, Ca2+ binds to troponin, altering its conformation and shfiting the troponin-tropomyosin complex. This shift in conformation exposes the myson binding sites on teh actin. Cross-bridges can thus form, undergo power strokes and produce muscle contraction.

ABC transporters:

A family of transport ATPases of great clinical importance are ABC transporters which have 2 ATP binding domains. ATP binding leads to dimerization of these 2 domains  Eucaryotes seem to use ABC transporters mostly for export such as hydrophobic drugs. This makes the control of malaria difficult because the protist responsible for causing this disease has amplified a gene encoding an ABC transporter that pumps out drugs used against it. In most vertebrate cells, an ABC transporter in the ER membrane transports a variety of peptides produced by protein degradation from the cytosol into the ER. The transported fragments are eventually carried to the cell surface where they are displayed for scrutiny by cytotoxic T lymphocytes. The disease cystic fibrosis is also caused by a mutation in a gene encoding an ABC transporter.

Secondary active transport: 

Some moleuels are moved against their concentration gradient by using the energy stored in a gradient of a different molecule. In this process called “coupled transport” the energy released as one molecule moves down its concentraiton gradient is captured and used to move a different molecule against its gradient.

As noted above, the energy stored in ATP moelcuels can be used to create a gradient of Na+ and K+ across the membrane. These gradeints can then be used to pwoer the transport of other molecuels across the membrane.

The active glucose transpoter uses the Na+ gradient produced by the Na+/K+ pump as a source of energy to power the movement of glucose into the cell. In this system, both glucose and Na+ bind to the transport protein, which allows Na+ to pass into the cell down its concetnraiton gradient, capturing the energya nd using it to move glucose into the cell. In this kind of cotransport, both molecuels are moving in teh same direction across the membrane, therefore the transporter is a symporter.

Na+ is the typical co-transported ion in the plasma cells of animals whose electrochemical gradient provides a driving force for the transport of a second molecule. The Na+ that enters the cell is subsequently pumped out by the ATP driven Na+ pump in the PM which by maintaining the Na+ gradient indirectly drives the transport. This is why such ion driven carriers are said to mediate “secondary active transport” whereas ATP driven carriers are said to mediate “active transport.” Secondary active transport can be coupled transport in the same direction (symporters). Examples of symporters include glucose carrier that is driven by a Na+ gradient. Epithelial cells pump glucose into the cell through the apical domain using a Na+ powered glucose symport (glucose then passes down its concentration gradient by passive transport by a different glucose carrier protein in the basal membrane domains). Secondary active transport can also be coupled transport in the opposite direction (antiporters). Most cells have one or more types of Na+ driven antiporters in their PM that help to maintain the cytosolic pH at around 7.2. These proteins use the energy stored in the Na+ gradient to pump out excess H+.