Calcium-activated potassium channels are a large family of potassium channels that are found throughout the central nervous system and in many other cell types. These channels are activated by rises in cytosolic calcium largely in response to calcium influx via voltage-gated calcium channels that open during action potentials. The International Union of Pharmacology has put the Ca2+ activated K+ channels into one large family which can be subdivided into two functionally but genetically unrelated groups. One group include Small conductance KCa channels (KCa 2.1 (SK1), 2.2 (SK2) and 2.3 (SK3)). These channels are sensitive to block by apamin (100 pM–10 nM), which distinguishes them from all other KCa channels. The group additionally is made up of Intermediate conductance channels (KCa3.1 (IK)). These channels are voltage-insensitive and are activated by low concentrations of internal calcium (less than 1.0 microM). Both IK and SK channels play roles in processes involving calcium-dependent signaling in both electrically excitable and nonexcitable cells. Unless they do not bind calcium directly they detect it by virtue of calmodulin, which is constitutively bound to the C-terminal region. Binding of calcium to this calmodulin results in conformational changes that are in turn responsible for channel gating. The second group of Ca2+ activated K+ channels include Large conductance KCa channels (KCa1.1, also known as BK channel, Slo or Slo1), a voltage-sensitive channel that binds calcium independently of calmodulin but mediated by at least three divalent cation binding sites in the cytoplasmic carboxyl domain of each channel subunit. Other members of this group are KCa4.1 (Slack or Slo2.2), KCa4.2 (Slick or Slo2.1), and KCa5.1 (Slo3).