Chapter 7 - Ca2+-activated K+ channels

Abstract

Here the Ca2+-activated potassium (KCa) channels are a structurally diverse group of K+ channels, which share the common property that they are activated by an increase in the intracellular Ca2+ concentration. KCa channels come in three major types that can be distinguished electrophysiologically by their vastly different single-channel conductances. The maxi KCa (or BK) channel is called so because of its large (big) single-channel conductance. By contrast, SK channels are insensitive to TEA1, but some—although not all— are blocked by apamin. IK channels are insensitive to apamin but blocked by CTX and clotrimazole. KCa channels contribute to the repolarization and after-hyperpolarization (AHP) of vertebrate neurones. The fast AHP regulates the interval between adjacent spikes. It is mediated by K+ channels that are activated, in response to depolarization and closely followed by repolarization. The slow AHP components are mediated by 125 SK and IK channels, which open in response to the elevation of submembrane [Ca2+] that results from Ca2+ entry during each action potential. Ca2+ accumulates during repetitive electrical activity, producing increased activation of SK currents and a larger AHP. There is evidence that SK3 channels may play a role in myotonic muscular dystrophy (MMD). Blocking Ca2+ influx with Cd2+ prevents SK channel activation and abolishes both the slow AHP and spike frequency adaptation. IK channels are not blocked by IBX or apamin, but are inhibited by CTX and Clotrimazole, which is currently in clinical trials for the treatment of sickle cell disease.