The aromatic binding site for tetraethylammonium ion on potassium channels

Neuron. 1992 Mar;8(3):483-91. doi: 10.1016/0896-6273(92)90276-j.


K+ channels are quite variable in their sensitivity to the pore-blocking agent tetraethylammonium ion (TEA) when it is applied to the extracellular side of the membrane. A Shaker K+ channel can be made highly sensitive by introducing a tyrosine (or phenylalanine) at residue 449 in each of the four subunits. A shift in the voltage dependence of blockade indicates that TEA senses a smaller fraction of the transmembrane electric field in the highly sensitive channels. There is a linear relationship between the free energy for TEA blockade and the number of subunits (zero, two, or four) containing tyrosine at 449, as if these four residues interact simultaneously with a TEA molecule to produce a high affinity binding site. The temperature dependence of blockade suggests that the interaction is not purely hydrophobic. These findings are consistent with a TEA-binding site formed by a bracelet of pore-lining aromatic residues. The center of the bracelet could bind a TEA molecule through a cation-pi orbital interaction.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • DNA Mutational Analysis
  • Drosophila melanogaster
  • Electric Conductivity
  • In Vitro Techniques
  • Ion Channel Gating
  • Membrane Potentials
  • Phenylalanine / chemistry
  • Potassium Channels / chemistry
  • Potassium Channels / metabolism*
  • Recombinant Proteins
  • Tetraethylammonium Compounds / metabolism*
  • Thermodynamics
  • Tyrosine / chemistry


  • Potassium Channels
  • Recombinant Proteins
  • Tetraethylammonium Compounds
  • Tyrosine
  • Phenylalanine