An overview of the potassium channel family

Abstract

Potassium channels, tetrameric integral membrane proteins that form aqueous pores through which K+ can flow, are found in virtually all organisms; the genomes of humans, Drosophila, and Caenorhabditis elegans contain 30-100 K+ channel genes each. The structure of a bacterial K+ channel, sequence comparisons with other channels and electrophysiological measurements have enabled conclusions about the mechanism of gating and ion flow to be drawn for many other channels.

Figure 1

Membrane topologies and main features of the K_v and K_ir potassium channel subtypes. (a, b) Schematic representation of the membrane topology of (a) K_v and (b) K_ir channels. Note that one subunit of the tetrameric structure is shown (see Figures 3b, 4). Transmembrane helices are numbered S1-S6 in K_v channels and M1 and M2 in K_ir channels; P, pore helix; S, signature sequence; N, amino terminus; C, carboxyl terminus; T1, conserved T1 domain (see Figure 4). The extracellular side is towards the top. Adapted with permission from [24].

Figure 2

Structure of the Streptomyces lividans K⁺ channel (KcsA). Labels are as in Figure 1. Reproduced with permission from [24].

Figure 3

(a) View of a hypothetical K_v-type K⁺ channel from the extracellular side of the membrane, showing the central pore-forming region, S5-P-S6, modeled by the structure of KcsA, surrounded by a voltage-gating domain of unknown structure, composed of S1-S4. Reproduced with permission from [25]. (b) Diagram of a typical K⁺ channel, showing the outward movement of the voltage-sensing transmembrane segment S4 concomitant with channel opening. Reproduced with permission from [26].

Figure 4

The amino-terminal T1 domain of K_v channels. (a, b) Structure of the soluble, isolated T1 domain of K_v 1.1 from Aplysia californica, with views along (a) the fourfold axis and (b) perpendicular to it. (c) Schematic diagram of the T1 domain location in the full-length K⁺ channel. Reproduced with permission from [18].