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

Nature. 2003 May 1;423(6935):42-8. doi: 10.1038/nature01581.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / immunology
  • Archaeal Proteins / chemistry
  • Archaeal Proteins / immunology
  • Archaeal Proteins / metabolism
  • Avidin / metabolism
  • Biotin / metabolism
  • Desulfurococcaceae / chemistry
  • Desulfurococcaceae / metabolism
  • Hydrophobic and Hydrophilic Interactions
  • Immunoglobulin Fab Fragments / immunology
  • Ion Channel Gating*
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Motion
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors
  • Potassium Channels, Voltage-Gated / chemistry*
  • Potassium Channels, Voltage-Gated / immunology
  • Potassium Channels, Voltage-Gated / metabolism*
  • Protein Structure, Tertiary
  • Static Electricity
  • Structure-Activity Relationship


  • Antibodies, Monoclonal
  • Archaeal Proteins
  • Immunoglobulin Fab Fragments
  • Potassium Channels, Voltage-Gated
  • Avidin
  • Biotin