title: A physical model of potassium channel activation: from energy landscape to gating kinetics.
abstract: We have developed a method for rapidly computing gating currents from a multiparticle ion channel model. Our approach is appropriate for energy landscapes that can be characterized by a network of well-defined activation pathways with barriers. To illustrate, we represented the gating apparatus of a channel subunit by an interacting pair of charged gating particles. Each particle underwent spatial diffusion along a bistable potential of mean force, with electrostatic forces coupling the two trajectories. After a step in membrane potential, relaxation of the smaller barrier charge led to a time-dependent reduction in the activation barrier of the principal gate charge. The resulting gating current exhibited a rising phase similar to that measured in voltage-dependent ion channels. Reduction of the two-dimensional diffusion landscape to a circular Markov model with four states accurately preserved the time course of gating currents on the slow timescale. A composite system containing four subunits leading to a concerted opening transition was used to fit a series of gating currents from the Shaker potassium channel. We end with a critique of the model with regard to current views on potassium channel structure.
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sigg
authors.forename: Francisco
authors.initials: F
authors.lastname: Bezanilla
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D003198:Computer Simulation; D004594:Electrophysiology / Q000379:methods; D004735:Energy Transfer / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D007700:Kinetics; D008390:Markov Chains; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D015233:Models, Statistical; D009010:Monte Carlo Method; D009865:Oocytes / Q000737:chemistry / Q000502:physiology; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology*; D011487:Protein Conformation; D021122:Protein Subunits; D051637:Shaker Superfamily of Potassium Channels; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D015221:Potassium Channels; D021122:Protein Subunits; D051637:Shaker Superfamily of Potassium Channels