All of these investigations should always be approached with the natural behavior and habitat of the organism in mind. The writing of this review was funded by the Max Planck Society. selleck screening library “
“Voltage-gated ion channels are transmembrane proteins that control and regulate the flow of small ions across cell membranes. They undergo conformational

changes in response to changes in the membrane potential, thereby allowing or blocking the passage of selected ions. Structurally, these channels are formed by four subunits surrounding a central aqueous pore for ion permeation. Each subunit comprises six transmembrane α-helical segments called S1 to S6. The first four α helices, S1–S4, constitute the voltage-sensing domain (VSD). VSDs respond to changes in the membrane potential by moving charged residues across the membrane field. Although there has been much progress over the last decade, atomic details of the voltage-sensing process are not known. Three idealized mechanistic models have been proposed to describe the voltage-sensing motion in voltage-gated K+ (Kv) channels (Tombola et al.,

2005). In the helical-screw/sliding-helix beta-catenin inhibitor model, the S4 segment is assumed to retain its helical conformation as its moves along its long axis (Ahern and Horn, 2004, Ahern and Horn, 2005 and Yarov-Yarovoy et al., 2006). In the transporter-like model, it is assumed that the translational movement of S4 is modest because the membrane field is focused over a small spatial region (Chanda et al., 2005). In the paddle model, the S3-S4 helix-turn-helix is assumed to undergo a fairly large displacement through the Liothyronine Sodium lipids (Jiang et al., 2003 and Ruta et al., 2005). Ultimately, to fully understand the mechanism of voltage activation, one needs knowledge of the three-dimensional structure of a channel in its various functional states. At a minimum, structures of the two main endpoints in

the conformational transitions, the active and resting states, are required to begin to understand voltage sensing. Yet, even for Kv channels, knowledge of those two conformations is currently incomplete. Atomic resolution X-ray structures of the Kv1.2 and the Kv1.2/Kv2.1 chimera channels provide information on the active-state conformation (Long et al., 2005 and Long et al., 2007). The available crystal structures show that the VSD is formed by four antiparallel helices (S1–S4), packed in a counterclockwise fashion as seen from the extracellular side. The first two arginine residues (R1 and R2) along the S4 helix are close to the membrane-solution interface, whereas the following two arginines (R3 and R4) are involved in electrostatic interactions with acidic residues in S2 and S3.