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A Physical Model of Potassium Channel Activation: From Energy Landscape to Gating Kinetics

Department of Physiology and Department of Anesthesiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095

Correspondence: Address reprint requests to Dr. Francisco Bezanilla, Dept. of Physiology, University of California at Los Angeles, 10833 Le Conte Ave., Los Angeles, CA 90095. Tel.: 310-825-2735; Fax: 310-794-9612; E-mail: fbezanil{at}ucla.edu.

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.

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