SK channel

SK channels (Small conductance calcium-activated potassium channels) are a subfamily of Ca2+-activated K+ channels. They are so called because of their small single channel conductance, ~10 pS. SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated (opened) by an increase in the concentration of intracellular calcium. Their activation limits the firing frequency of action potentials and are important for regulating afterhyperpolarization in central neurons and other types of electrically excitable cells. SK channels are thought to be involved in synaptic plasticity and therefore play important roles in memory and learning.

Structure
SK potassium channels share the same basic architecture with shaker-like voltage-gated potassium channels. Four subunits associate to form a tetramer. Each of the subunits has six hydrophobic alpha helical domains which insert into the cell membrane. A loop between the fifth and sixth transmembrane domain forms the potassium ion selectivity filter. SK channels may assemble as homoterameric channels or as heterotetrameric channels, consisting of more than one SK channel subtype. In addition, SK potassium channels are tightly associated with the protein calmodulin which accounts for the calcium sensitivity of these channels.

Classification
The SK channel family contains 4 members - SK1, SK2, SK3, and SK4. SK4 is often referred to as IK (Intermediate conductance) due to its higher conductance 20 - 80 pS.

Blockers
All SK channels can be pharmacologically blocked by quaternary ammonium salts of a plant-derived neurotoxin bicuculline. In addition, SK channels(SK1-SK3) are sensitive to blockade by the bee venom apamin, but SK4 (IK) is not. and the scorpion venom tamapin.

Modulators
Allosteric modulators of SK channels work by changing the apparent calcium sensitivity of the channels. Examples include:
 * Non selective positive modulators of SK channels: EBIO (1-Ethyl-2-BenzimIdazolinOne), NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime)
 * SK-3 selective positive modulators : CyPPA (NS6277; Cyclohexyl-(2-(3,5-dimethyl-Pyrazol-1-yl)-6-methyl-Pyrimidin-4-yl)-Amine)