Ion channel

The archetypal channel pore is just one or two atoms wide at its narrowest point and is selective for specific species of ion, such as sodium or potassium.

However, some channels may be permeable to the passage of more than one type of ion, typically sharing a common charge: positive (cations) or negative (anions).

In many ion channels, passage through the pore is governed by a "gate", which may be opened or closed in response to chemical or electrical signals, temperature, or mechanical force.

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.

Indeed, numerous 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.

[13] Absence or mutation of one or more of the contributing types of channel subunits can result in loss of function and, potentially, underlie neurologic diseases.

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.

[citation needed] The existence and mechanism for ion selectivity was first postulated in the late 1960s by Bertil Hille and Clay Armstrong.

[34][35][36][37][38] The idea of the ionic selectivity for potassium channels was that the carbonyl oxygens of the protein backbones of the "selectivity filter" (named by Bertil Hille) could efficiently replace the water molecules that normally shield potassium ions, but that sodium ions were smaller and cannot be completely dehydrated to allow such shielding, and therefore could not pass through.

The determination of the molecular structure of KcsA by Roderick MacKinnon using X-ray crystallography won a share of the 2003 Nobel Prize in Chemistry.

[39] 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.

The fundamental properties of currents mediated by ion channels were analyzed by the British biophysicists Alan Hodgkin and Andrew Huxley as part of their Nobel Prize-winning research on the action potential, published in 1952.

[44][45] The existence of ion channels was confirmed in the 1970s by Bernard Katz and Ricardo Miledi using noise analysis [citation needed].

In recent years the development of automated patch clamp devices helped to increase significantly the throughput in ion channel screening.

[49] Markov chain analysis can be used to make conclusions regarding the nature of a given ion channel, including the likely number of open and closed states.

[50] We can also use Markov chain analysis to produce models that accurately simulate the insertion of ion channels into cell membranes.

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 .
Structure of the KcsA potassium channel ( PDB: 1K4C ). The two gray planes indicate the hydrocarbon boundaries of the lipid bilayer and were calculated with the ANVIL algorithm. [ 5 ]
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 determined by MacKinnon's group in 2001.