The aromatic binding site for tetraethylammonium ion on potassium channels

doi:10.1016/0896-6273(92)90276-J

Neuron

Volume 8, Issue 3, March 1992, Pages 483-491

https://doi.org/10.1016/0896-6273(92)90276-J Get rights and content

Abstract

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-π orbital interaction.

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Neuron

Abstract

References (27)

Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons

J. Gen. Physiol.

Anomalous rectification in squid giantaxon injected with tetraethylammonium chloride

J. Gen. Physiol.

The inner quaternary ammonium ion receptor in potassium channels of the node of Ranvier

J. Gen. Physiol.

Biophysical Chemistry. Part 1: The Conformation of Biological Macromolecules

Acetylcholine binding by a synthetic receptor: implications for biological recognition

Science

A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning

Nature

Blockage of squid axon potassium conductance by internal tetra-N-alkylammonium ions of various sizes

Biophys. J.

The selective inhibition of delayed potassium currents in nerve by tetraethylammonium ion

J. Gen. Physiol.

Biophysical and molecular mechanisms of Shaker potassium channel inactivation

Science

Evidence for the formation of heteromultimeric potassium channels in Xenopus oocytes

Nature

Multiple products of the Drosophila Shaker gene may contribute to potassium channel diversity

Neuron

Interaction between tetraethylammonium and amino acid residues in the pore of cloned voltage-dependent potassium channels

J. Biol. Chem.

Rapid and efficient site-specific mutagenesis without phenotypic selection

Cited by (403)

Photopharmacological approaches for dissecting potassium channel physiology

A fine-tuned azobenzene for enhanced photopharmacology in vivo

Ligand modulation of KCNQ-encoded (K<inf>V</inf>7) potassium channels in the heart and nervous system

Highlighting membrane protein structure and function: A celebration of the protein data bank

Tethered peptide toxins for ion channels

Carvedilol blockage of delayed rectifier Kv2.1 channels and its molecular basis

Neuron

ArticleThe aromatic binding site for tetraethylammonium ion on potassium channels

Abstract

Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons

J. Gen. Physiol.

Anomalous rectification in squid giantaxon injected with tetraethylammonium chloride

J. Gen. Physiol.

The inner quaternary ammonium ion receptor in potassium channels of the node of Ranvier

J. Gen. Physiol.

Biophysical Chemistry. Part 1: The Conformation of Biological Macromolecules

Acetylcholine binding by a synthetic receptor: implications for biological recognition

Science

A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning

Nature

Blockage of squid axon potassium conductance by internal tetra-N-alkylammonium ions of various sizes

Biophys. J.

The selective inhibition of delayed potassium currents in nerve by tetraethylammonium ion

J. Gen. Physiol.

Biophysical and molecular mechanisms of Shaker potassium channel inactivation

Science

Evidence for the formation of heteromultimeric potassium channels in Xenopus oocytes

Nature

Multiple products of the Drosophila Shaker gene may contribute to potassium channel diversity

Neuron

Interaction between tetraethylammonium and amino acid residues in the pore of cloned voltage-dependent potassium channels

J. Biol. Chem.

Rapid and efficient site-specific mutagenesis without phenotypic selection

Article
The aromatic binding site for tetraethylammonium ion on potassium channels