Environment of the gating charges in the Kv1.2 Shaker potassium channel
1Equipe de Dynamique des Assemblages Membranaires, Unité Mixte de Recherche CNRS/UHP 7565 Université Henri-Poincaré, 54506 Vandoeuvre-lès-Nancy, France.
Abstract:
Recently, the structure of the Shaker channel Kv1.2 has been determined at a 2.9-angstroms resolution. This opens new possibilities in deciphering the mechanism underlying the function of voltage-gated potassium (Kv) channels. Molecular dynamics simulations of the channel, embedded in a membrane environment show that the channel is in its open state and that the gating charges carried by S4 are exposed to the solvent. The hydrated environment of S4 favors a local collapse of the electrostatic potential, which generates high electric-field gradients around the arginine gating charges. Comparison to experiments suggests furthermore that activation of the channel requires mainly a lateral displacement of S4. Overall, the results agree with the transporter model devised for Kv channels from electrophysiology experiments, and provide a possible pathway for the mechanistic response to membrane depolarization.
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