Mutation of a glutamate receptor motif reveals its role in gating and delta2 receptor channel properties

Nat Neurosci. 2000 Apr;3(4):315-22. doi: 10.1038/73877.

Abstract

Despite its importance in the cerebellum, the functions of the orphan glutamate receptor delta2 are unknown. We examined a mutant delta2 receptor channel in lurcher mice that was constitutively active in the absence of ligand. Because this mutation was within a highly conserved motif (YTANLAAF), we tested its effect on several glutamate receptors. Mutant delta2 receptors showed distinct channel properties, including double rectification of the current-voltage relationship, sensitivity to a polyamine antagonist and moderate Ca 2+ permeability, whereas other constitutively active mutant glutamate channels resembled wild-type channels in these respects. Moreover, the kinetics of ligand-activated currents were strikingly altered. We conclude that the delta2 receptor has a functional ion channel pore similar to that of glutamate receptors. The motif may have a role in the channel gating of glutamate receptors.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Antihypertensive Agents / pharmacology
  • Benzodiazepines*
  • Benzothiadiazines / pharmacology
  • Cell Line
  • Conserved Sequence
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / pharmacology
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / genetics*
  • Kainic Acid / analogs & derivatives
  • Kainic Acid / pharmacology
  • Kidney / cytology
  • Mice
  • Mice, Neurologic Mutants
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Neuromuscular Depolarizing Agents / pharmacology
  • Patch-Clamp Techniques
  • Purkinje Cells / chemistry
  • Purkinje Cells / physiology
  • Quinoxalines / pharmacology
  • Receptors, Glutamate / chemistry
  • Receptors, Glutamate / genetics*
  • Receptors, Glutamate / metabolism*
  • Transfection

Substances

  • Anti-Anxiety Agents
  • Antihypertensive Agents
  • Benzothiadiazines
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Neuromuscular Depolarizing Agents
  • Quinoxalines
  • Receptors, Glutamate
  • glutamate receptor delta 2
  • GYKI 52466
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Benzodiazepines
  • Glutamic Acid
  • Dizocilpine Maleate
  • domoic acid
  • cyclothiazide
  • Kainic Acid