title: Persistent GABAA/C responses to gabazine, taurine and beta-alanine in rat hypoglossal motoneurons.
abstract: In hypoglossal motoneurons, a sustained anionic current, sensitive to a blocker of ρ-containing GABA receptors, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) and insensitive to bicuculline, was previously shown to be activated by gabazine. In order to better characterize the receptors involved, the sensitivity of this atypical response to pentobarbital (30μM), allopregnanolone (0.3μM) and midazolam (0.5μM) was first investigated. Pentobarbital potentiated the response, whereas the steroid and the benzodiazepine were ineffective. The results indicate the involvement of hybrid heteromeric receptors, including at least a GABA receptor ρ subunit and a γ subunit, accounting for the pentobarbital-sensitivity. The effects of the endogenous β amino acids, taurine and β-alanine, which are released under various pathological conditions and show neuroprotective properties, were then studied. In the presence of the glycine receptor blocker strychnine (1μM), both taurine (0.3-1mM) and β-alanine (0.3mM) activated sustained anionic currents, which were partly blocked by TPMPA (100μM). Thus, both β amino acids activated ρ-containing GABA receptors in hypoglossal motoneurons. Bicuculline (20μM) reduced responses to taurine and β-alanine, but small sustained responses persisted in the presence of both strychnine and bicuculline. Responses to β-alanine were slightly increased by allopregnanolone, indicating a contribution of the bicuculline- and neurosteroid-sensitive GABAA receptors underlying tonic inhibition in these motoneurons. Since sustained activation of anionic channels inhibits most mature principal neurons, the ρ-containing GABA receptors permanently activated by taurine and β-alanine might contribute to some of their neuroprotective properties under damaging overexcitatory situations.
authors.affiliation: U1195 Inserm Univ. Paris-Sud, 80 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre, France. Electronic address: dominique.chesnoy@inserm.fr.
authors.forename: D
authors.initials: D
authors.lastname: Chesnoy-Marchais
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology; D002713:Chlorine / Q000378:metabolism; D018682:GABA Agents / Q000494:pharmacology*; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000378:metabolism; D008874:Midazolam / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology; D013654:Taurine / Q000494:pharmacology / Q000502:physiology*; D046509:Tissue Culture Techniques; D015091:beta-Alanine / Q000494:pharmacology*
chemical_list: C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; D002491:Central Nervous System Agents; D018682:GABA Agents; C087200:GABA-C receptor; D018696:Neuroprotective Agents; D010721:Phosphinic Acids; D011724:Pyridazines; D011725:Pyridines; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D015091:beta-Alanine; D013654:Taurine; D002713:Chlorine; C049853:gabazine; D011280:Pregnanolone; D013331:Strychnine; D010424:Pentobarbital; D008874:Midazolam; D001640:Bicuculline
keywords: GABA(C) receptor; gabazine; hybrid GABA receptor; motoneuron; taurine; tonic inhibition