GAT-1 acts to limit a tonic GABA(A) current in rat CA3 pyramidal neurons at birth.
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.
Sipilä
Sampsa T
ST
Department of Biological and Environmental Sciences, University of Helsinki, FIN-00014 Helsinki, Finland. Sampsa.Sipila@Helsinki.Fi
Voipio
Juha
J
Kaila
Kai
K
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
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