Bicuculline- and phaclofen-sensitive components of N-methyl-D-aspartate-induced hyperpolarizations in rat dorsolateral septal nucleus neurones.
1. Intracellular recordings were made from rat dorsolateral septal nucleus (DLSN) neurones in vitro. Pressure application (puff) of N-methyl-D-aspartate (NMDA) usually produced a hyperpolarization followed by a depolarization in normal Mg2+ solution. 2. A hyperpolarizing response and a depolarizing response could be evoked separately by appropriate positioning of the puff pipette. The NMDA-induced hyperpolarization was blocked by a low-Ca2+ solution or a tetrodotoxin (TTX)-containing solution, but under these conditions the NMDA-induced depolarization was spared. The amplitude of NMDA-induced hyperpolarizations was 7.7 +/- 2.7 mV (n = 13) at the resting membrane potential level. 3. An NMDA-induced hyperpolarization had two components. A fast component reversed at about -76 mV and a slow component reversed at -90 mV. The reversal potential of the slow component shifted in the depolarizing direction of hyperpolarizing direction when the slice was bathed in a high or low-K+ solution, respectively. 4. The reversal potentials of NMDA-induced hyperpolarizations were similar to the synaptic potentials evoked by fimbrial stimulation. The reversal potentials of the fast and slow components were close to the IPSP reversal potential (-70 mV) and the late hyperpolarizing potential (LHP) reversal potential (-95 mV), respectively. 5. NMDA-induced hyperpolarizations were blocked by the specific NMDA receptor antagonist 2-amino-5-phosphonopontanoate (APV). The fast component of an NMDA-induced hyperpolarization was blocked by the specific GABAA receptor antagonist, bicuculline, and the slow component was depressed by the specific GABAB receptor antagonist, phaclofen. 6. Glutamate receptor subtype-specific agonists, such as kainate or quisqualate, could induce similar hyperpolarizations which had bicuculline-sensitive and insensitive components. These non-NMDA-type agonist-induced hyperpolarizations were not affected by APV (50 microM) but were blocked by kynurenic acid (1 mM). 7. We conclude that these excitatory amino acid-induced hyperpolarizations observed in the rat DLSN are mediated by GABAergic interneurones which have both non-NMDA-type and NMDA-type receptors.
Gallagher
J P
JP
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Hasuo
H
H
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D012686:Septal Nuclei / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C052329:phaclofen; D001224:Aspartic Acid; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D001418:Baclofen; D001640:Bicuculline