Depolarizing Actions of GABA in Immature Neurons Depend Neither on Ketone Bodies Nor on Pyruvate

Roman Tyzio (1) , Camille Allène (1) , Romain Nardou (1) , Michel A. Picardo (1) , Sumii Yamamoto (1) , Sudhir Sivakumaran , Maddalena D Caiati , Sylvain Rheims (1) , Marat Minlebaev (1) , Mathieu Milh (1) , Pascal Ferré (2) , Rustem Khazipov (1) , Jean-Louis Romette (3) , Jean Lorquin (4) , Rosa Cossart (1) , Ilgam Khalilov (1) , Astrid Nehlig (5) , Enrico Cherubini , Yehezkel Ben-Ari (1)

1 INMED - INSERM U1249 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]
2 CRC (UMR_S 872) - Centre de Recherche des Cordeliers
3 ESIL - Ecole Supérieure d'Ingénieurs de Luminy
4 MIO - Institut méditerranéen d'océanologie
5 Physiopathologie clinique et expérimentale de la schizophrénie

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 M) 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.

Domaines: Neurobiologie

Roman Tyzio, Camille Allène, Romain Nardou, Michel A. Picardo, Sumii Yamamoto, et al.. Depolarizing Actions of GABA in Immature Neurons Depend Neither on Ketone Bodies Nor on Pyruvate. Journal of Neuroscience, 2011, 31 (1), pp.34-45. ⟨10.1523/JNEUROSCI.3314-10.2011⟩. ⟨hal-01848215⟩