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