title: GAT-1 acts to limit a tonic GABA(A) current in rat CA3 pyramidal neurons at birth.
abstract: Tonic activation of GABA(A) receptors takes place before the development of functional synapses in cortical structures. We studied whether inefficient GABA uptake might explain the presence of a tonic GABA(A)-mediated current (I(GABA-A)) in early postnatal hippocampal pyramidal neurons. The data show, however, that the tonic I(GABA-A) is enhanced by the specific blocker of GABA transporter-1 (GAT-1), NO-711 (1-[2-[[(Diphenylmethyleneimino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride), at birth in rat CA3 pyramidal neurons. NO-711 also prolonged the duration of GABA transients during endogenous hippocampal network events (known as giant depolarizing potentials) at postnatal day 0. The endogenous tonic I(GABA-A) was seen and it was enhanced by NO-711 in the presence of tetrodotoxin, which itself had only a minor effect on the holding current under control conditions. This indicates that the source of interstitial GABA is largely independent of action-potential activity. The tonic I(GABA-A) in neonatal CA3 pyramidal neurons was increased by zolpidem, indicating that at least a proportion of the underlying GABA(A) receptors contain gamma2 and alpha1-alpha3 subunits. The present data point to a significant role for GAT-1 in the control of the excitability of immature hippocampal neurons and networks.
authors.affiliation: Department of Biological and Environmental Sciences, University of Helsinki, FIN-00014 Helsinki, Finland. Sampsa.Sipila@Helsinki.Fi
authors.forename: Sampsa T
authors.initials: ST
authors.lastname: Sipilä
authors.forename: Juha
authors.initials: J
authors.lastname: Voipio
authors.forename: Kai
authors.initials: K
authors.lastname: Kaila
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D009557:Nipecotic Acids / Q000494:pharmacology; D009924:Organ Culture Techniques; D010091:Oximes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D009557:Nipecotic Acids; D010091:Oximes; D011963:Receptors, GABA-A; C493415:Slc6a1 protein, rat; C078793:NNC 711; D013779:Tetrodotoxin