Protonation of histidine groups inhibits gating of the quisqualate/kainate channel protein in isolated catfish cone horizontal cells

Neuron. 1990 Oct;5(4):471-8. doi: 10.1016/0896-6273(90)90086-u.


Increases in the extracellular hydrogen ion concentration ([H+]o) but not the intracellular concentration ([H+]i) antagonized the inward going membrane currents recorded from isolated cone horizontal cells during application of quisqualate, alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid, and kainate. The pK determined from a titration curve was 6.5 with a slope greater than 1, indicating protonation of several histidines. The reduction in membrane current was voltage-independent. The affinity of the agonist for the receptor, the single-channel conductance, and the open time were unaffected by [H+]o. [H+]o antagonism was not the result of charge neutralization such as screening surface charge. Diethylpyrocarbonate, a histidine-modifying reagent, reduced the agonist-induced current, but disulfide- and sulfhydryl-modifying reagents were ineffective. These results suggest that histidine groups on the external face of the channel protein provide a functional site regulating channel gating.

Publication types

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

MeSH terms

  • Animals
  • Catfishes
  • Cell Separation
  • Histidine / metabolism*
  • Hydrogen / antagonists & inhibitors
  • Ion Channel Gating*
  • Ion Channels / metabolism*
  • Kainic Acid / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Photoreceptor Cells / cytology
  • Photoreceptor Cells / metabolism*
  • Protons*
  • Quisqualic Acid / metabolism*


  • Ion Channels
  • Nerve Tissue Proteins
  • Protons
  • Histidine
  • Hydrogen
  • Quisqualic Acid
  • Kainic Acid