Two populations of kainate receptors with separate signaling mechanisms in hippocampal interneurons.
Consistent with the epileptogenic and deleterious effects of the potent neurotoxin kainate, the activation of kainate receptors reduces the synaptic inhibition induced by the amino acid gamma-aminobutyric acid (GABA). Extrapolating from these data led to the conclusion that kainate receptors are located presynaptically. However, kainate directly depolarizes the inhibitory interneurons, causing them to fire repeatedly. This effect might indirectly decrease the size of inhibitory postsynaptic currents recorded from pyramidal cells and places in doubt the presynaptic location for kainate receptors. Here we show that both effects, membrane depolarization and the reduction of inhibitory potentials, can be dissociated by several means, particularly by the natural agonist of kainate receptors, glutamate. Indeed, when applied at low concentrations, glutamate inhibited GABA release without affecting the firing rate of GABA interneurons. These results indicate that CA1 interneurons contain two populations of kainate receptors, each with different agonist sensitivity and coupled to distinct signaling pathways.
Rodríguez-Moreno
A
A
Instituto Cajal, Consejo Superior de Investigaciones Científicas, Avenida Doctor Arce 37, 28002-Madrid, Spain.
López-García
J C
JC
Lerma
J
J
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000187:drug effects / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D007211:Indoles / Q000494:pharmacology; D007395:Interneurons / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000145:classification* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011422:Propionates / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000819:agonists / Q000145:classification* / Q000502:physiology; D017661:Receptors, Presynaptic / Q000145:classification / Q000502:physiology; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015763:2-Amino-5-phosphonovalerate; D001569:Benzodiazepines; D001640:Bicuculline; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007211:Indoles; D007555:Isoxazoles; D007608:Kainic Acid; D008012:Lidocaine; D008301:Maleimides; D009281:Naphthalenes; D009419:Nerve Tissue Proteins; D011422:Propionates; D011493:Protein Kinase C; D018092:Kainic Acid Receptors; D017661:Receptors, Presynaptic; D019311:Staurosporine; D010566:Virulence Factors, Bordetella; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005680:gamma-Aminobutyric Acid; C081662:alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate; C079692:GYKI 53655; C012647:QX-314; C118651:GYKI 53784; C058819:calphostin C; C088060:bisindolylmaleimide