Calcium-activated potassium channel

Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that Calcium levels inside of a cell could affect the permeability of potassium through that cell membrane. Then in 1970, Meech was the first to observe that intracellular calcium could trigger potassium currents. In humans they are divided into three subtypes large conductance or BK channels, which have very high conductance which range from 100 to 300 pS, intermediate conductance or IK channels, with intermediate conductance ranging from 25 to 100 pS, and small conductance or SK channels with small conductances from 2-25 pS. Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that Calcium levels inside of a cell could affect the permeability of potassium through that cell membrane. Then in 1970, Meech was the first to observe that intracellular calcium could trigger potassium currents. In humans they are divided into three subtypes large conductance or BK channels, which have very high conductance which range from 100 to 300 pS, intermediate conductance or IK channels, with intermediate conductance ranging from 25 to 100 pS, and small conductance or SK channels with small conductances from 2-25 pS. This family of ion channels is, for the most part, activated by intracellular Ca2+ and contains 8 members in the human genome. However, some of these channels (the KCa4 and KCa5 channels) are responsive instead to other intracellular ligands, such as Na+, Cl−, and pH. Furthermore, multiple members of family are both ligand and voltage activated, further complicating the description of this family. The KCa channel α subunits have six or seven transmembrane segments, similar to the KV channels but occasionally with an additional N-terminal transmembrane helix. The α subunits make homo- and hetero-tetrameric complexes. The calcium binding domain may be contained in the α subunit sequence, as in KCa1, or may be through an additional calcium binding protein such as calmodulin. Knowing the structure of these channels can provide insight into their function and mechanism of gating. They are made up of two different subunits, alpha and beta. The alpha subunit is a tetramer which forms the pore, the voltage sensor, and the calcium sensing region. This subunit of the channel is made up of seven trans-membrane units, and a large intracellular region. The voltage sensor is made by the S4 transmembrane region, which has several Arginine residues which act to ‘sense’ the changes in charge and move in a very similar way to other voltage gated potassium channels. As they move in response to the voltage changes they open and close the gate. The linker between the S5 and S6 region serves to form the pore of the channel. Inside of the cell, the main portion to note is the calcium bowl. This bowl is thought to be the site of calcium binding. The beta subunit of the channel is thought to be a regulatory subunit of the channel. There are four different kinds of the beta subunit, 1, 2, 3, and, 4. Beta 2 and 3 are inhibitory, while beta 1 and 4 are excitatory, or they cause the channel to be more open than not open. The excitatory beta subunits affect the alpha subunits in such a way that the channel seldom inactivates. Below is a list of the 8 known human calcium-activated potassium channel grouped according to sequence homology of transmembrane hydrophobic cores: Though not implied in the name, but implied by the structure these channels can also be activated by voltage. The different modes of activation in these channels are thought to be independent of one another. This feature of the channel allows them to participate in many different physiologic functions. The physiological effects of BK channels have been studied extensively using knockout mice. In doing so it was observed that there were changes in the blood vessels of the mice. The animals without the BK channels showed increased mean arterial pressure and vascular tone. These findings indicate that BK channels are involved in the relaxation of smooth muscle cells. In any muscle cell, increased intracellular calcium causes contraction. In smooth muscle cells the elevated levels of intracellular calcium cause the opening of BK channels which in turn allow potassium ions to flow out of the cell. This causes further hyperpolarization and closing of voltage gated calcium channels, relaxation can then occur. The knockout mice also experienced intention tremors, shorter stride length, and slower swim speed. All of these are symptoms of ataxia, indicating that BK channels are highly important in the cerebellum.