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Ion channels are pore-forming that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping and other electrical signals by gating the flow of across the cell membrane, controlling the flow of ions across secretion and , and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophore proteins, the other being .
The study of ion channels often involves biophysics, electrophysiology, and pharmacology, while using techniques including voltage clamp, patch clamp, immunohistochemistry, X-ray crystallography, fluoroscopy, and RT-PCR. Their classification as molecules is referred to as channelomics.
Ion channels are integral membrane proteins, typically formed as assemblies of several individual proteins. Such "multi-protein 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. (2025). 9780878937417, Sinauer Associates Inc.. ISBN 9780878937417 (1999). 9780397518203, Lippincott-Raven. ISBN 9780397518203 For most voltage-gated ion channels, the pore-forming subunit(s) are called the α subunit, while the auxiliary subunits are denoted β, γ, and so on.
Further heterogeneity of ion channels arises when channels with different constitutive Protein subunit give rise to a specific kind of current. 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.
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Ion channels activated by second messengers may also be categorized in this group, although ligands and second messengers are otherwise distinguished from each other.
/ref> 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 late 1960s by Bertil Hille and Clay Armstrong. 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. This mechanism was finally confirmed when the first structure of an ion channel was elucidated. A bacterial potassium channel KcsA, consisting of just the selectivity filter, "P" loop, and two transmembrane helices was used as a model to study the permeability and the selectivity of ion channels in the Mackinnon lab. The determination of the molecular structure of KcsA by Roderick MacKinnon using 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. 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.
Channels can have single (CLICs) to multiple transmembrane (K channels, P2X receptors, Na channels) domains which span plasma membrane to form pores. Pore can determine the selectivity of the channel. Gate can be formed either inside or outside the pore region.
The existence of ion channels was confirmed in the 1970s by Bernard Katz and Ricardo Miledi using noise analysis . It was then shown more directly 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 significantly the throughput in ion channel screening.
The Nobel Prize in Chemistry for 2003 was awarded to Roderick MacKinnon for his studies on the physico-chemical properties of ion channel structure and function, including x-ray crystallographic structure studies.
A particularly relevant form of stochastic processes in the study of ion channels is . In a Markov chain, there are multiple states, each of which has given chances to transition to different states over a particular period of time. Ion channels undergo state transitions (e.g. open, closed, inactive) that behave like Markov chains. 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. We can also use Markov chain analysis to produce models that accurately simulate the insertion of ion channels into cell membranes.
Markov chains can also be used in combination with the stochastic matrix to determine the stable distribution matrix by solving the equation PX=X, where P is the stochastic matrix and X is the stable distribution matrix. This stable distribution matrix tells us the relative frequencies of each state after a long time, which in the context of ion channels can be the frequencies of the open, closed, and inactive states for an ion channel. Note that Markov chain assumptions apply, including that (1) all transition probabilities for each state sum to one, (2) the probability model applies to all possible states, and (3) that the probability of transitions are constant over time. Therefore, Markov chains have limited applicability in some situations.
There are a variety of other stochastic processes that are utilized in the study of ion channels, but are too complex to relate here and can be examined more closely elsewhere.
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