Ion channels are present in the membranes that surround all biological cells. By conducting and controlling the flow of ions, these pore-forming proteins help establish the small negative voltage that all cells possess at rest (see cell potential). Drawing of a cell membrane A component of every biological cell, the cell membrane (or plasma membrane) is a thin and structured bilayer of phospholipid and protein molecules that encapsulate the cell. ... Cells in culture, stained for keratin (red) and DNA (green) The cell is the structural and functional unit of all living organisms. ... ion (disambiguation) An ion is an atom or group of atoms with a net electric charge. ... A pore, in general, is some form of opening, usually very small. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... In the physical sciences, potential difference is the difference in potential between two points in a conservative vector field. ... In biological cells that are electrically at rest, the cytosol possesses a uniform electric potential or voltage compared to the extracellular solution. ...

Basic features

An ion channel 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 related proteins closely packed around a water-filled pore through the plane of the membrane or lipid bilayer. While large-pore channels permit the passage of ions more or less indiscriminately, 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 fast as the ions move through free fluid. Access to the pore is governed by "gates," which may be opened or closed by chemical or electrical signals, or mechanical force, depending on the variety of channel. Integral membrane protein of the transmembrane type An Integral Membrane Protein (IMP) is a protein molecule (or assembly of proteins) that in most cases spans the biological membrane with which it is associated (especially the plasma membrane) or which, in any case, is sufficiently embedded in the membrane to remain... In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles (or coassembles) with other protein molecules to form a multimeric or oligomeric protein. ... Two or more structures are said to be homologous if they are alike because of shared ancestry. ... A DPPC bilayer simulation Color scheme: PO4 = green, N(CH3)3 = violet, water = blue, terminal CH3 = yellow, O = red, glycol C = brown, chain C = grey In biology and chemistry, a lipid bilayer is a membrane or zone of membrane composed only of lipid. ... General Name, Symbol, Number sodium, Na, 11 Series alkali metal Group, Period, Block 1 (IA), 3 , s Density, Hardness 968 kg/m3, 0. ... General Name, Symbol, Number potassium, K, 19 Series alkali metals Group, Period, Block 1(IA), 4 , s Density, Hardness 856 kg/m3, 0. ...

Biological role

Because "voltage-gated" channels underlie the nerve impulse and because "transmitter-gated" 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 plugging ion channel pores. But ion channels figure in a wide variety of biological processes that involve rapid changes in cells. In the search for any drug, ion channels are a favorite target. Schematic of an electrophysiological recording of an action potential showing the various phases which occur as the wave passes a point on a cell membrane. ... Synapses allow nerve cells to communicate with one another through axons and dendrites, converting electrical signals into chemical ones. ... The nervous system of an animal coordinates the activity of the muscles, monitors the organs, constructs and processes input from the senses, and initiates actions. ...

Diversity and activation

• Voltage-gated channels sense the transmembrane potential and open or close in response to depolarization or hyperpolarization, respectively. Examples include the sodium and potassium voltage-gated channels of nerve and muscle, and the voltage-gated calcium channels that control neurotransmitter release in pre-synaptic endings.
• Ligand-gated channels open in response to a specific ligand molecule on the external face of the membrane in which the channel resides. Examples include the "nicotinic" Acetylcholine receptor, AMPA receptor and other neurotransmitter-gated channels.
• Cyclic nucleotide-gated channels, Calcium-activated channels and others open in response to internal solutes and mediate cellular responses to second messengers.
• Stretch-activated channels open or close in response to mechanical forces that arise from local stretching or compression of the membrane around them; for example when their cells swell or shrink. Such channels are believed to underlie touch sensation and the transduction of acoustic vibrations into the sensation of sound.
• G-protein-gated channels open in response to G protein-activation via its receptor. An example is the "muscarinic" Acetylcholine receptor
• Inward-rectifier K channels allow potassium to flow into the cell in an inwardly rectifying manner. They are involved in important physiological processes such as the pacemaker activity in the heart, insulin release, and potassium uptake in glial cells.
• Light-gated channels like channelrhodopsin are directly opened by the action of light

Certain channels respond to multiple influences. For instance, the NMDA receptor is partially activated by interaction with its ligand, glutamate, but is also voltage-sensitive and only conducts when the membrane is depolarized. Some calcium-sensitive potassium channels respond to both calcium and depolarization, with an excess of one apparently being sufficient to overcome an absence of the other. Voltage-gated ion channel is a ion channel that is specifically activated, or gated, by the surrounding potential difference near the channel (or near the cell, neuron or synapse). ... In membrane biophysics sometimes used interchangeably with cell potential, but applicable to any lipid bilayer or membrane. ... Schematic of an electrophysiological recording of an action potential showing the various phases which occur as the wave passes a point on a cell membrane. ... Schematic of an electrophysiological recording of an action potential showing the various phases which occur as the wave passes a point on a cell membrane. ... In cell biology, potassium channels are the most common type of ion channel. ... Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a presynaptic and a postsynaptic neuron. ... Synapses allow nerve cells to communicate with one another through axons and dendrites, converting electrical signals into chemical ones. ... Ligand-gated ion channel is a broad term that refers to any ion channel that is gated (i. ... An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine by opening a pathway in the membrane for the diffusion of ions across the cell membrane. ... The AMPA receptor (AMPAR) is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system. ... Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a presynaptic and a postsynaptic neuron. ... A Cyclic nucleotide-gated ion channel is any ion channel that opens in the presence of cyclic nucleotides. ... In biology, second messengers are low-weight diffusible molecules that are used in signal transduction to relay a signal within a cell. ... G-proteins, short for guanine nucleotide binding proteins, are a family of proteins involved in second messenger cascades. ... An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine by opening a pathway in the membrane for the diffusion of ions across the cell membrane. ... Channelrhodopsin-2 (ChR2) is a unique protein, in that it is an ion channel that is directly opened by light. ... The NMDA receptor (NMDAR) is an ionotropic receptor for glutamate (NMDA is a name of its selective specific agonist). ... Glutamic acid or glutamate is one of the 20 most common natural amino acids. ...

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 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. Within an integral membrane protein, a transmembrane helix is a segment that is alpha-helical in structure, roughly 20 amino acids in length and (though it may be presumed to lie within the protein, out of contact with the surrounding lipid bilayer) is said to span the membrane. ... Dr. Roderick MacKinnon (born 1956 in Burlington, Massachusetts) An award-winning scientist, in the biophysics field, he has produced groundbreaking research detailing the way the bodys electrical systems function, by unlocking the secrets of the bodys ion channel proteins. ... Crystallography (from the Greek words crystallon = solid and graphein = write) is the experimental science of determining the arrangement of atoms in solids. ... List of Nobel Prize laureates in Chemistry from 1901 to the present day. ...

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. 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. Electrophysiology is the science and branch of physiology that pertains to the flow of ions in biological tissues and, in particular, to the electrical recording techniques that enable the measurement of this flow. ... Biochemistry is the chemistry of life. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... This article is about mutation in biology, for other meanings see: mutation (disambiguation). ...

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. Channel's existence 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 enzymes work. Biophysics (also biological physics) is an interdisciplinary science that applies theories and methods of the physical sciences to questions of biology. ... Sir Alan Lloyd Hodgkin (February 5, 1914 _ December 20, 1998) was a British physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his work with Andrew Fielding Huxley on the basis of nerve action potentials, the electrical impulses that enable the activity of an... Sir Andrew Fielding Huxley OM FRS (born 22 November 1917, Hampstead, London, England, UK) is a British physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his work with Alan Lloyd Hodgkin on the basis of nerve action potentials, the electrical impulses that enable the... List of Nobel Prize laureates in Physiology or Medicine from 1901 to the present day. ... Events and trends Although in the United States and in many other Western societies the 1970s are often seen as a period of transition between the turbulent 1960s and the more conservative 1980s and 1990s, many of the trends that are associated widely with the Sixties, from the Sexual Revolution... Electrophysiology is the science and branch of physiology that pertains to the flow of ions in biological tissues and, in particular, to the electrical recording techniques that enable the measurement of this flow. ...

See also

• transmembrane receptor
• passive transport
• active transport
• Action potential

Transmembrane receptors are integral membrane proteins, which reside and operate typically within a cells plasma membrane, but also in the membranes of some subcellular compartments and organelles. ... Passive transport is a means of moving biochemicals, and other atomic or molecular substances, across membranes. ... Active transport is the mediated transport of biochemicals, and other atomic/molecular substances, across membranes. ... Schematic of an electrophysiological recording of an action potential showing the various phases which occur as the wave passes a point on a cell membrane. ...

External links

• The Voltage Sensor in Voltage-Dependent Ion Channels (http://physrev.physiology.org/cgi/content/full/80/2/555)
• X-ray crystal structure of a potassium channel (http://www.cellbio.wustl.edu/faculty/huettner/69.pdf)
• Ion Channel, Biophysics and Electrophysiology Resources (http://www.ionchannels.org)