title: Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate.
abstract: GABA depolarizes immature neurons because of a high [Cl(-)](i) and orchestrates giant depolarizing potential (GDP) generation. Zilberter and coworkers (Rheims et al., 2009; Holmgren et al., 2010) showed recently that the ketone body metabolite DL-3-hydroxybutyrate (DL-BHB) (4 mM), lactate (4 mM), or pyruvate (5 mM) shifted GABA actions to hyperpolarizing, suggesting that the depolarizing effects of GABA are attributable to inadequate energy supply when glucose is the sole energy source. We now report that, in rat pups (postnatal days 4-7), plasma D-BHB, lactate, and pyruvate levels are 0.9, 1.5, and 0.12 mM, respectively. Then, we show that DL-BHB (4 mM) and pyruvate (200 μM) do not affect (i) the driving force for GABA(A) receptor-mediated currents (DF(GABA)) in cell-attached single-channel recordings, (2) the resting membrane potential and reversal potential of synaptic GABA(A) receptor-mediated responses in perforated patch recordings, (3) the action potentials triggered by focal GABA applications, or (4) the GDPs determined with electrophysiological recordings and dynamic two-photon calcium imaging. Only very high nonphysiological concentrations of pyruvate (5 mM) reduced DF(GABA) and blocked GDPs. Therefore, DL-BHB does not alter GABA signals even at the high concentrations used by Zilberter and colleagues, whereas pyruvate requires exceedingly high nonphysiological concentrations to exert an effect. There is no need to alter conventional glucose enriched artificial CSF to investigate GABA signals in the developing brain.
authors.affiliation: Inserm, Unité 901/Institut de Neurobiologie de Méditerranée, 13273 Marseille, France.
authors.forename: Roman
authors.initials: R
authors.lastname: Tyzio
authors.forename: Camille
authors.initials: C
authors.lastname: Allene
authors.forename: Romain
authors.initials: R
authors.lastname: Nardou
authors.forename: Michel A
authors.initials: MA
authors.lastname: Picardo
authors.forename: Sumii
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Sudhir
authors.initials: S
authors.lastname: Sivakumaran
authors.forename: Maddalena D
authors.initials: MD
authors.lastname: Caiati
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rheims
authors.forename: Marat
authors.initials: M
authors.lastname: Minlebaev
authors.forename: Mathieu
authors.initials: M
authors.lastname: Milh
authors.forename: Pascal
authors.initials: P
authors.lastname: Ferré
authors.forename: Rustem
authors.initials: R
authors.lastname: Khazipov
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Romette
authors.forename: Jean
authors.initials: J
authors.lastname: Lorquin
authors.forename: Rosa
authors.initials: R
authors.lastname: Cossart
authors.forename: Ilgam
authors.initials: I
authors.lastname: Khalilov
authors.forename: Astrid
authors.initials: A
authors.lastname: Nehlig
authors.forename: Enrico
authors.initials: E
authors.lastname: Cherubini
authors.forename: Yehezkel
authors.initials: Y
authors.lastname: Ben-Ari
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000097:blood; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000254:growth & development; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D019289:Pyruvic Acid / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D007657:Ketone Bodies; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide; D019344:Lactic Acid; D005680:gamma-Aminobutyric Acid; D019289:Pyruvic Acid; D002118:Calcium; D020155:3-Hydroxybutyric Acid; D001640:Bicuculline