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Nature 423, 42-48 (1 May 2003) | doi:10.1038/nature01581; Received 19 February 2003; Accepted 11 March 2003

The principle of gating charge movement in a voltage-dependent K+ channel

Youxing Jiang1, Vanessa Ruta, Jiayun Chen, Alice Lee & Roderick MacKinnon

  1. Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
  2. Present address: University of Texas Southwestern Medical Center, Department of Physiology, 5323 Harry Hines Blvd, Dallas, Texas 75390-9040, USA.

Correspondence to: Roderick MacKinnon Correspondence and requests for materials should be addressed to R.M. (Email: mackinn@rockvax.rockefeller.edu).

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The steep dependence of channel opening on membrane voltage allows voltage-dependent K+ channels to turn on almost like a switch. Opening is driven by the movement of gating charges that originate from arginine residues on helical S4 segments of the protein. Each S4 segment forms half of a 'voltage-sensor paddle' on the channel's outer perimeter. Here we show that the voltage-sensor paddles are positioned inside the membrane, near the intracellular surface, when the channel is closed, and that the paddles move a large distance across the membrane from inside to outside when the channel opens. KvAP channels were reconstituted into planar lipid membranes and studied using monoclonal Fab fragments, a voltage-sensor toxin, and avidin binding to tethered biotin. Our findings lead us to conclude that the voltage-sensor paddles operate somewhat like hydrophobic cations attached to levers, enabling the membrane electric field to open and close the pore.