Ca2+-Sensitive Potassium Channels

Abstract

The Ca²⁺ ion is used ubiquitously as an intracellular signaling molecule due to its high external and low internal concentration. Many Ca²⁺-sensing ion channel proteins have evolved to receive and propagate Ca²⁺ signals. Among them are the Ca²⁺-activated potassium channels, a large family of potassium channels activated by rises in cytosolic calcium in response to Ca²⁺ influx via Ca²⁺-permeable channels that open during the action potential or Ca²⁺ release from the endoplasmic reticulum. The Ca²⁺ sensitivity of these channels allows internal Ca²⁺ to regulate the electrical activity of the cell membrane. Activating these potassium channels controls many physiological processes, from the firing properties of neurons to the control of transmitter release. This review will discuss what is understood about the Ca²⁺ sensitivity of the two best-studied groups of Ca²⁺-sensitive potassium channels: large-conductance Ca²⁺-activated K⁺ channels, K_Ca1.1, and small/intermediate-conductance Ca²⁺-activated K⁺ channels, K_Ca2.x/K_Ca3.1.

Keywords: Ca2+ sensitivity; Ca2+-activated potassium channels; KCa 1.1; KCa2.x and KCa3.1 channels; channelopathies.

Figure 1

Expression and Physiology of the K_Ca2x, K_Ca3.1, and K_Ca1.1 channels [10].

Figure 2

Diagram of the general K_Ca1.1 and K_Ca2.x channel structure. (A) Schematic channel topology of one K_Ca 1.1 α-subunit, including the pore-gate domain between (S5–S6) and a C-terminal cytosolic region that functions as a Ca²⁺ sensor constituted by two non-identical domains (RCK1 and RCK2), which contain high-affinity binding Ca²⁺ sites (Ca²⁺ bowl) and several domains for multiple ligands or cations such as Mg²⁺. (B) Schematic channel topology of one K_Ca2.x α-subunit, including the CaM that serves as the K_Ca2.x and K_Ca3.1 channel’s Ca²⁺ sensor. A and B were generated using Biorender.com.

Figure 3

The regulation of K_Ca2.X Channels’ Ca²⁺ sensitivity.