Antiporter illustration

An antiporter (also called exchanger or counter-transporter) is an integral membrane protein which is involved in secondary active transport of two or more different molecules or ions (i.e. solutes) across a phospholipid membrane such as the plasma membrane in opposite directions.

In secondary active transport, one species of solute moves along its electrochemical gradient, allowing a different species to move against its own electrochemical gradient. This movement is in contrast to primary active transport, in which all solutes are moved against their concentration gradients, fueled by ATP.

Transport may involve one or more of each type of solute. For example, the Na + /Ca 2+ exchanger , used by many cells to remove cytoplasmic calcium, exchanges one calcium ion for three sodium ions.

Facilitated diffusion

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Facilitated diffusion in cell membrane, showing ion channels and carrier proteins

Facilitated diffusion (or facilitated transport) is a process of diffusion, a form of passive transport facilitated by transport proteins. Facilitated diffusion is the spontaneous passage of molecules or ions across a biological membrane passing through specific transmembrane transport proteins. The facilitated diffusion may occur either across biological membranes or through aqueous compartments of an organism.

Polar molecules and charged ions are dissolved in water but they can not diffuse freely across cell membranes due to the hydrophobic nature of the phospholipids that make up the lipid bilayers. Only small nonpolar molecules, such as oxygen can diffuse easily across the membrane. All polar molecules are transported across membranes by proteins that form transmembrane channels. These channels are gated so they can open and close, thus regulating the flow of ions or small polar molecules. Larger molecules are transported by transmembrane carrier proteins, such as permeases that change their conformation as the molecules are carried through, for example glucose or amino acids.

Non-polar molecules, such as retinol or fatty acids are poorly soluble in water. They are transported through aqueous compartments of cells or through extracellular space by water-soluble carriers as retinol binding protein. The metabolites are not changed because no energy is required for facilitated diffusion. Only permease changes its shape in order to transport the metabolites. The form of transport through cell membrane which modifies its metabolites is the group translocation transportation.Passive transport

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Passive transport means moving biochemicals and atomic or molecular substances across the cell membrane. Unlike active transport, this process does not involve chemical energy. The four main kinds of passive transport are diffusion, facilitated diffusion, filtration and osmosis.

Diffusion

[edit] Facilitated Diffusion

Facilitated diffusion on a cell membrane.Main article: Facilitated diffusion

goes from high to low concentration.

Facilitated diffusion is the movement of molecules across the cell membrane via special transport proteins that are embedded within the cellular membrane. Many large molecules, such as glucose, are insoluble in lipids and too large to fit through the membrane pores. Therefore, it will bind with its specific carrier proteins, and the complex will then be bonded to a receptor site and moved through the cellular membrane. The facilitated diffusion is a passive process, and the solutes still move down the concentration gradient.

[edit] Filtration

Main article: Filtration

Filtration is movement of water and solute molecules across the cell membrane due to hydrostatic pressure generated by the cardiovascular system. Depending on the size of the membrane pores, only solutes of a certain size may pass through it. For example, the membrane pores of the Bowman's capsule in the kidneys are very small, and only albumins, the smallest of the proteins, have any chance of being filtered through. On the other hand, the membrane pores of liver cells are extremely large, to allow a variety of solutes to pass through and be metabolized.

[edit] Osmosis

Effect of osmosis on blood cells under different solutions.Main article: Osmosis

Osmosis is the diffusion of water molecules across a selectively permeable membrane. The net movement of water molecules through a partially permeable membrane from a solution of high water potential to an area of low water potential. A cell with a less negative water potential will draw in water but this depends on other factors as well such as solute potential (pressure in the cell e.g. solute molecules) and pressure potential (external pressure e.g. cell wall)

Active transport

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The action of the sodium-potassium pump is an example of primary active transport.

Active transport is the mediated process of moving particles across a biological membrane against a concentration gradient. If the process uses chemical energy, such as from adenosine triphosphate (ATP), it is termed primary active transport. Secondary active transport involves the use of an electrochemical gradient. Active transport uses energy, unlike passive transport, which does not use any energy.

] Details

Specialized trans-membrane proteins recognize the substance to be transported and allow it (or, in the case of secondary transport, expend energy on forcing it) to cross the membrane when it otherwise would not, either because it is one to which the lipid bilayer of the membrane is impermeable or because it is moved against the concentration gradient. The last case, known as primary active transport, and the proteins involved in it as pumps, uses the chemical energy of, usually, ATP. The other cases, which usually derive their energy through exploitation of an electrochemical gradient, are known as secondary active transport and involve pore-forming proteins which form channels through the cell membrane.

Sometimes one substance is transported in one direction at the same time as another substance is being cotransported in the other direction. This is called antiport. Symport is the name if two substrates are being transported in the same direction across the membrane. Antiport and symport are associated with secondary active transport, meaning that one of the two substances are transported against its concentration gradient utilizing the energy derived from the transport of the second substance (mostly Na+, K+ or H+) down its concentration gradient.

When particles are being moved from areas of low concentration to areas of high concentration (i.e. against the concentration gradient) then specific carrier proteins in the membrane are required to move these particles. The carrier proteins bind to specific molecules (e.g. glucose) and transport them into the cell where they are released. Because energy is required for this process, it is known as active transport. Examples of active transport include when sodium is transported out of the cell and potassium into the cell by the sodium-potassium pump. Active transport often takes place in the internal lining of the small intestine.

Plants need to absorb mineral salts from the soil, but these salts are in very dilute solution. Active transport enables these cells to take up salts from this dilute solution against the concentration gradient.

[edit] P-type ATPases

P-type ATPases mainly transport cations across membranes, such as Na+, K+, Ca2+ and H+. They are primary active transporters. They consist of one transmembrane domain, and at least three cytosolic domains called the A, P and N domain. They use the energy of ATP to power the active extrusion of cations from the cytosol and the uptake of counter-ions from the non-cytosolic side. The best known example of a P-type ATPase is the sodium-potassium pump responsible for the generation of the electrochemical gradient of sodium and potassium across animal plasma-membranes. This pump uses one molecule of ATP to first extrude 3 Na+ ions from the cytosol and then import 2 K+ ions into the cytosol (Note that this is not an example of antiport (described above), as the Na+ and K+ are transported as two distinct events during the reaction cycle). The electrochemical gradient generated by the sodium potassium pump is used to power all secondary active transport in amimal cells, for osmotic regulation, and for the generation of action potentials in neurons.

[edit] ABC pumps

ABC class pumps transport small molecules across membranes. They are also called the ABC superfamily and are an example of primary active transporters. They consist of two transmembrane domains, and two ATP binding domains. ABC pumps are involved in the transport of small molecules, phospholipids, and lipophilic drugs in mammalian cells. In bacteria they transport amino acids, sugars, and peptides.[1]

[edit] Examples Water , ethanol, and chloroform are simple molecules that do not require active transport to cross a membrane.

Metal ions, such as Na+, K+, Mg2+, or Ca2+, require ion pumps or ion channels to cross membranes and distribute through the body

In the epithelial cells of the stomach, gastric acid is produced by hydrogen potassium ATPase, a proton pump[citation needed]

[edit] EndocytosisFor more details on this topic, see Endocytosis.

Endocytosis is the process by which cells ingest materials. The cellular membrane folds around the desired materials outside the cell. The ingested particle is trapped within a pouch, vacuole or inside the cytoplasm. Often enzymes from lysosomes are then used to digest the molecules absorbed by this process.

Endocyctosis can be split up into two main types: pinocytosis and phagocytosis.

In pinocytosis, cells engulf liquid particles (in humans this process occurs in the small intestine, cells there engulf fat droplets)

In phagocytosis, cells engulf solid particles.

[edit] ExocytosisFor more details on this topic, see Exocytosis.

Exocytosis is the process by which cells excrete waste and other large molecules from the protoplasm

Active Transport

Saturday, February 14, 2009

Active Transport

Active transport is the movement of molecules up their concentration gradient, using energy.

Concentration Gradients

The concentration of most molecules inside a cell is different than the concentration of molecules in the surrounding environment. The plasma membrane separates the internal environment of the cell from the fluid bathing the cell and regulates the flow of molecules both into and out of the cell. The second law of thermodynamics states that molecules, whether in the gas or liquid state, will move spontaneously from an area of higher concentration to an area of lower concentration or down their concentration gradient.

A concentration gradient can be likened to water stored behind a dam. The water behind the dam will flow through the dam via any available channel to the other side. The energy from the water moving through the dam can be harnessed to make electricity. Water can also be pumped in the opposite direction from the river below the dam up to the reservoir behind the dam, with an expenditure of energy. Cellular membranes act somewhat like a dam. They block the movement of many types of molecules and have specific channels, transporters and pumps to provide pathways for the movement of certain molecules across the membrane.

When a molecule moves down its concentration gradient using one of these membrane channels or transporters, the process is called facilitated diffusion. In facilitated diffusion, no input of energy is needed to move the molecules. Instead, the potential energy of the concentration gradient powers the movement, just like water flowing out of a dam. For further diffusion, the channel or transporter does not determine in which direction the molecules will move, it only provides a pathway for the movement.

In cells, some molecules must be moved against their concentration gradient to increase their concentration inside or outside the cell. This process requires the input of energy and is known as active transport. As with facilitated diffusion, special transporters in the membrane are used to move the molecules across the membrane. The plasma membrane is not the only cellular membrane that requires active transport. All organelles surrounded by membranes must concentrate some molecules against their concentration gradients.

Types of Active Transporters

There are three types of active transporters in cells: (1) Coupled transporters link the “downhill” transport of one molecule to the “uphill” transport of a different molecule; (2) ATP-driven pumps use the energy stored in adenosine triphosphate (ATP) to move molecules across membranes; (3) Light-driven pumps use the energy from photons of light to move molecules across membranes. Light driven pumps are found mainly in certain types of bacterial cells.

Most of the energy expended by a cell in active transport is used to pump ions out of the cell across the plasma membrane. Because ions have an electrical charge, they do not easily cross membranes. This phenomenon allows large ion concentration differences to be built up across a membrane. Highly selective transporters are present in membranes that pump certain ions up their concentration gradients, but ignore other ions.

The NA+-K+ Pump. One of the best understood active transport systems is the sodium-potassium pump, or NA+-K+ pump. This carrier protein is a coupled transporter that moves sodium ions out of the cell while simultaneously moving potassium ions into the cell. Because of the pump, the sodium ion concentration inside the cell is about ten to thirty times lowerthan the concentration of sodium ions in the fluid surrounding the cell. The concentration of potassium ions inside the cell is almost exactly the opposite, with a ten- to thirtyfold higher concentration of potassium ions inside the cell than outside.

Because the cell is pumping sodium from a region of lower concentration (inside) to a region of higher concentration (outside), the NA+-K+ pump must use energy to carry out its pumping activity, and this energy is supplied by ATP. For this reason, the +-K+ pump is also considered an enzyme. It belongs to a class of enzymes known as ATPases that use the energy stored in ATP to carry out another action. Other membrane transporters use the energy from ATP to pump ions like calcium, amino acids, and other electrically charged molecules either into or out of the cell.

Ions carry a positive or negative electrical charge so that these gradients have two components: a concentration gradient and a voltage or electrical gradient. For instance, sodium ions are positively charged. The higher concentration of sodium ions outside of the cell than inside means that outside of the cell will have a positive charge and the inside of the cell will have a negative charge. This potential difference, or voltage, across the membrane can be used as an energy source to move other charged molecules. Positively charged molecules will be attracted towards the inside of the cell and negatively charged molecules will be attracted to the outside of the cell. It is, in fact, this electrical potential that causes positively charged potassium ions to enter the cell through the Na-K pump, even though they are moving up their concentration gradient.

The potential energy of the gradient can be used to produce ATP or to transport other molecules across membranes. One of the most important uses of the NA+ gradient is to power the transport of glucose into the cell. The NA+-glucose cotransporter moves sodium down its concentration gradient, and glucose up its gradient, as both move into the cell.

Ion channel

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Jump to: navigation, searchAnother, unrelated ion channeling process is part of ion implantation.

Not to be confused with: Ion Television.

Schematic diagram of an ion channel. 1 - channel domains (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane.

Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cells (see cell potential) by allowing the flow of ions down their electrochemical gradient.[1] They are present in the membranes that surround all biological cells. The study of ion channels is known as channelomics and involves many scientific techniques such as voltage clamp electrophysiology (in particular patch clamp), immunohistochemistry, and RT-PCR.

Basic features

Ion channels regulate the flow of ions across the membrane in all cells. It is an integral membrane protein; or, more typically, an assembly of several proteins. Such "multi-subunit" assemblies usually involve a circular arrangement of identical or homologous proteins closely packed around a water-filled pore through the plane of the membrane or lipid bilayer.[2][3] The pore-forming subunit(s) are called the α subunit, while the auxiliary subunits are denoted β, γ, and so on. While some channels permit the passage of ions based solely on charge, the archetypal channel pore is just one or two atoms wide at its narrowest point. It conducts a specific species of ion, such as sodium or potassium, and conveys them through the membrane single file--nearly as quickly as the ions move through free fluid. In some ion channels, passage through the pore is governed by a "gate," which may be opened or closed by chemical or electrical signals, temperature, or mechanical force, depending on the variety of channel.

Biological role

Because "voltage-activated" channels underlie the nerve impulse and because "transmitter-activated" channels mediate conduction across the synapses, channels are especially prominent components of the nervous system. Indeed, most of the offensive and defensive toxins that organisms have evolved for shutting down the nervous systems of predators and prey (e.g., the venoms produced by spiders, scorpions, snakes, fish, bees, sea snails and others) work by modulating ion channel conductance and/or kinetics. In addition, ion channels are key components in a wide variety of biological processes that involve rapid changes in cells, such as cardiac, skeletal, and smooth muscle contraction, epithelial transport of nutrients and ions, T-cell activation and pancreatic beta-cell insulin release. In the search for new drugs, ion channels are a frequent target.[4][5][6]

Diversity

Ion channels may be classified by the nature of their gating, the species of ions passing through those gates, and the number of gates (pores).

By gating

Ion channels may be classified by gating, i.e. what opens and closes the channels. Voltage-gated ion channels activate/inactivate depending on the voltage gradient across the plasma membrane, while ligand-gated ion channels activate/inactivate depending on binding of ligands to the channel.

Voltage-gatedMain article: Voltage-gated ion channel

Voltage-gated channels open and close in response to membrane potential.

Voltage-gated sodium channels : This family contains at least 9 members and is largely responsible for action potential creation and propagation. The pore-forming α subunits are very large (up to 4,000 amino acids) and consist of four homologous repeat domains (I-IV) each comprising six transmembrane segments (S1-S6) for a total of 24 transmembrane segments. The members of this family also coassemble with auxiliary β subunits, each spanning the membrane once. Both α and β subunits are extensively glycosylated.

Voltage-gated calcium channels : This family contains 10 members, though these members are known to coassemble with α2δ, β, and γ subunits. These channels play an important role in both linking muscle excitation with contraction as well as neuronal excitation with transmitter release. The α subunits have an overall structural resemblance to those of the sodium channels and are equally large.

o Cation channels of sperm : This small family of channels, normally referred to as Catsper channels, is related to the two-pore channels and distantly related to TRP channels.

Voltage-gated potassium channels (KV): This family contains almost 40 members, which are further divided into 12 subfamilies. These channels are known mainly for their role in repolarizing the cell membrane following action potentials. The α subunits have six transmembrane segments, homologous to a single domain of the sodium channels. Correspondingly, they assemble as tetramers to produce a functioning channel.

Some transient receptor potential channels: This group of channels, normally referred to simply as TRP channels, is named after their role in Drosophila phototransduction. This family, containing at least 28 members, is incredibly diverse in its method of activation. Some TRP channels seem to be constitutively open, while others are gated by voltage, intracellular Ca2+, pH, redox state, osmolarity, and mechanical stretch. These channels also vary according to the ion(s) they pass, some being selective for Ca2+ while others are less selective, acting as cation channels. This family is subdivided into 6 subfamilies based on homology: classical (TRPC), vanilloid receptors (TRPV), melastatin (TRPM), polycystins (TRPP), mucolipins (TRPML), and ankyrin transmembrane protein 1 (TRPA).

Hyperpolarization-activated cyclic nucleotide-gated channels: The opening of these channels is due to hyperpolarization rather than the depolarization required for other cyclic nucleotide-gated channels. These channels are also sensitive to the cyclic nucleotides cAMP and cGMP, which alter the voltage sensitivity of the channel’s opening. These channels are permeable to the monovalent cations K+ and Na+. There are 4 members of this family, all of which form tetramers of six-transmembrane α subunits. As these channels open under hyperpolarizing conditions, they function as pacemaking channels in the heart, particularly the SA node.

Voltage-gated proton channels : Voltage-gated proton channels openin with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be acid extrusion from

cells. Another important function occurs in phagocytes (e.g. eosinophils, neutrophils, macrophages) during the "respiratory burst." When bacteria or other microbes are engulfed by phagocytes, the enzyme NADPH oxidase assembles in the membrane and begins to produce reactive oxygen species (ROS) that help kill bacteria. NADPH oxidase is electrogenic, moving electrons across the membrane, and proton channels open to allow proton flux to balance the electron movement electrically.

Ligand-gatedMain article: Ligand-gated ion channel

Also known as ionotropic receptors, this group of channels open in response to specific ligand molecules binding to the extracellular domain of the receptor protein. Ligand binding causes a conformational change in the structure of the channel protein that ultimately leads to the opening of the channel gate and subsequent ion flux across the plasma membrane. Examples of such channels include the cation-permeable "nicotinic" Acetylcholine receptor, ionotropic glutamate-gated receptors and ATP-gated P2X receptors, and the anion-permeable γ-aminobutyric acid-gated GABAA receptor.

Ion channels activated by second messengers may also be categorized in this group, although ligands and second messengers are otherwise distinguished from each other.

Other gating

Other gating include activation/inactivation by e.g. second messengers from the inside of the cell membrane, rather as from outside, as in the case for ligands. Ions may count to such second messengers, and then causes direct activation, rather than indirect, as in the case were the electric potential of ions cause activation/inactivation of voltage-gated ion channels.

Some potassium channels o Inward-rectifier potassium channels : These channels allow potassium to flow into the cell in an inwardly

rectifying manner, i.e, potassium flows effectively into, but not out of, the cell. This family is composed of 15 official and 1 unofficial members and is further subdivided into 7 subfamilies based on homology. These channels are affected by intracellular ATP, PIP2, and G-protein βγ subunits. They are involved in important physiological processes such as the pacemaker activity in the heart, insulin release, and potassium uptake in glial cells. They contain only two transmembrane segments, corresponding to the core pore-forming segments of the KV and KCa channels. Their α subunits form tetramers.

o Calcium-activated potassium channels : This family of channels is, for the most part, activated by intracellular Ca2+ and contains 8 members.

o Two-pore-domain potassium channels : This family of 15 members form what is known as leak channels, and they follow Goldman-Hodgkin-Katz (open) rectification.

Light-gated channels like channelrhodopsin are directly opened by the action of light.

Mechanosensitive ion channels are opening under the influence of stretch, pressure, shear, displacement.

Cyclic nucleotide-gated channels : This superfamily of channels contains two families: the cyclic nucleotide-gated (CNG) channels and the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. It should be noted that this grouping is functional rather than evolutionary.

o Cyclic nucleotide-gated channels: This family of channels is characterized by activation due to the binding of intracellular cAMP or cGMP, with specificity varying by member. These channels are primarily permeable to monovalent cations such as K+ and Na+. They are also permeable to Ca2+, though it acts to close them. There are 6 members of this family, which is divided into 2 subfamilies.

o Hyperpolarization-activated cyclic nucleotide-gated channels

By ions

Chloride channels : This superfamily of poorly-understood channels consists of approximately 13 members.

Potassium channels o Voltage-gated potassium channels o Calcium-activated potassium channels o Inward-rectifier potassium channels o Two-pore-domain potassium channels : This family of 15 members form what is known as leak

channels, and they follow Goldman-Hodgkin-Katz (open) rectification.

Sodium channels

Calcium channels

Proton channels o Voltage-gated proton channels

General ion channels: These are relatively non-specific for ions and thus let many types of ions through the channel.

o Most Transient receptor potential channels

Other classifications

There are other types of ion channel classifications that are based on less normal characteristics, e.g. multiple pores and transient potentials.

Almost all ion channels have one single pore. However, there are also those with two:

Two-pore channels : This small family of 2 members putatively forms cation-selective ion channels. They are predicted to contain two KV-style six-transmembrane domains, suggesting they form a dimer in the membrane. These channels are related to catsper channels channels and, more distantly, TRP channels.

There are channels that are classified by the duration of the response to stimuli:

Transient receptor potential channels : This group of channels, normally referred to simply as TRP channels, is named after their role in Drosophila phototransduction. This family, containing at least 28 members, is incredibly diverse in its method of activation. Some TRP channels seem to be constitutively open, while others are gated by voltage, intracellular Ca2+, pH, redox state, osmolarity, and mechanical stretch. These channels also vary according to the ion(s) they pass, some being selective for Ca2+ while others are less selective, acting as cation channels. This family is subdivided into 6 subfamilies based on homology: canonical (TRPC), vanilloid receptors (TRPV), melastatin (TRPM), polycystins (TRPP), mucolipins (TRPML), and ankyrin transmembrane protein 1 (TRPA).

Detailed structure

Channels differ with respect to the ion they let pass (for example, Na+, K+, Cl−), the ways in which they may be regulated, the number of subunits of which they are composed and other aspects of structure. Channels belonging to the largest class, which includes the voltage-gated channels that underlie the nerve impulse, consists of four subunits with six transmembrane helices each. On activation, these helices move about and open the pore. Two of these six helices are separated by a loop that lines the pore and is the primary determinant of ion selectivity and conductance in this channel class and some others. The existence and mechanism for ion selectivity was first postulated in the 1960s by Clay Armstrong. The channel subunits of one such other class, for example, consist of just this "P" loop and two transmembrane helices. The determination of their molecular structure by Roderick MacKinnon using X-ray crystallography won a share of the 2003 Nobel Prize in Chemistry.

Because of their small size and the difficulty of crystallizing integral membrane proteins for X-ray analysis, it is only very recently that scientists have been able to directly examine what channels "look like." Particularly in cases where the crystallography required removing channels from their membranes with detergent, many researchers regard images that have been obtained as tentative. An example is the long-awaited crystal structure of a voltage-gated potassium channel, which was reported in May 2003. The detailed 3D structure of the magnesium channel from bacteria can be seen here. One inevitable ambiguity about these structures relates to the strong evidence that channels change conformation as they operate (they open and close, for example), such that the structure in the crystal could represent any one of these operational states. Most of what researchers have deduced about channel operation so far they have established through electrophysiology, biochemistry, gene sequence comparison and mutagenesis.

Diseases of Ion Channels

There are a number of chemicals and genetic disorders which disrupt normal functioning of ion channels and have disastrous consequences for the organism. Genetic disorders of ion channels and their modifiers are known as Channelopathies. See Category:Channelopathy for a full list.

Chemicals

Tetrodotoxin (TTX), used by puffer fish and some types of newts for defense. It blocks sodium channels. Saxitoxin , is produced by a dinoflagellate also known as "red tide". It blocks voltage dependent sodium

channels. Conotoxin , is used by cone snails to hunt prey. Lidocaine and Novocaine belong to a class of local anesthetics which block sodium ion channels. Dendrotoxin is produced by mamba snakes, and blocks potassium channels. Iberiotoxin is produced by the Buthus tamulus and blocks potassium channels. Heteropodatoxin is produced by Heteropoda venatoria and blocks potassium channels.

Genetic

Shaker gene mutations cause a defect in the voltage gated ion channels, slowing down the repolarization of the cell.

Equine hyperkalaemic periodic paralysis as well as Human hyperkalaemic periodic paralysis (HyperPP) are caused by a defect in voltage dependent sodium channels.

Paramyotonia congenita (PC) and potassium aggravated myotonias (PAM) Generalized epilepsy with febrile seizures plus (GEFS+) Episodic Ataxia (EA), characterized by sporadic bouts of severe discoordination with or without myokymia,

and can be provoked by stress, startle, or heavy exertion such as exercise. Familial hemiplegic migraine (FHM) Spinocerebellar ataxia type 13 Long QT syndrome is a ventricular arrhythmia syndrome caused by mutations in one or more of presently ten

different genes, most of which are potassium channels and all of which affect cardiac repolarization. Brugada syndrome is another ventricular arrhythmia caused by voltage-gated sodium channel gene mutations. Cystic fibrosis is caused by mutations in the CFTR gene, which is a chloride channel. Mucolipidosis type IV is caused by mutations in the gene encoding the TRPML1 channel

History

The existence of ion channels was hypothesized by the British biophysicists Alan Hodgkin and Andrew Huxley as part of their Nobel Prize-winning theory of the nerve impulse, published in 1952. The existence of ion channels was confirmed in the 1970s with an electrical recording technique known as the "patch clamp," which led to a Nobel Prize to Erwin Neher and Bert Sakmann, the technique's inventors. Hundreds if not thousands of researchers continue to pursue a more detailed understanding of how these proteins work. In recent years the development of automated patch clamp devices helped to increase the throughput in ion channel screening significantly.

The Nobel Prize in Chemistry for 2003 was awarded to two American scientists: Roderick MacKinnon for his studies on the physico-chemical properties of ion channel function, including x-ray crystallographic structure studies and Peter Agre for his similar work on aquaporins.[7]

The ion channel in fine art

Birth of an Idea (2007) by Julian Voss-Andreae. The sculpture was commissioned by Roderick MacKinnon based on the molecule's atomic coordinates that were deposited by MacKinnon's group in 2001.

Roderick MacKinnon commissioned "Birth of an Idea," a 5' (1.50 m) tall sculpture based on the KcsA potassium channel. The artwork contains a wire object representing the pore liner with a blown glass object representing the main cavity of the channel std

The pathway of receptor mediated endocytosis

http://srs.dl.ac.uk/VUV/home-page/hot-topics/microfluorimeter.html