Voltage-dependent potassium channels are essential for the generation of nerve impulses1. Voltage sensitivity is conferred by charged residues located mainly in the fourth transmembrane segment (S4) of each of the four identical subunits that make up the channel. These charged segments relocate when the potential difference across the membrane changes2,3, controlling the ability of the pore to conduct ions. In the crystal structure of the Aeropyrum pernix potassium channel KvAP4, the S4 and part of the third (S3B) transmembrane α-helices are connected by a hairpin turn in an arrangement termed the ‘voltage-sensor paddle’. This structure was proposed to move through the lipid bilayer during channel activation, transporting positive charges across a large fraction of the membrane5. Here we show that replacing the first S4 arginine by histidine in the Shaker potassium channel creates a proton pore when the cell is hyperpolarized. Formation of this pore does not support the paddle model, as protons would not have access to a lipid-buried histidine. We conclude that, at hyperpolarized potentials, water and protons from the internal and external solutions must be separated by a narrow barrier in the channel protein that focuses the electric field to a small voltage-sensitive region.
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This work was supported by the National Institutes of Health.
The authors declare that they have no competing financial interests.
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Starace, D., Bezanilla, F. A proton pore in a potassium channel voltage sensor reveals a focused electric field. Nature 427, 548–553 (2004). https://doi.org/10.1038/nature02270
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