Depolarizing Actions of GABA in Immature Neurons Depend Neither on Ketone Bodies Nor on Pyruvate - Aix-Marseille Université Access content directly
Journal Articles Journal of Neuroscience Year : 2011

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

Sudhir Sivakumaran
  • Function : Author
Maddalena D Caiati
  • Function : Author
Pascal Ferré
Jean Lorquin
Enrico Cherubini
  • Function : Author

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 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.

Domains

Neurobiology
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Dates and versions

hal-01848215 , version 1 (24-07-2018)

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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⟩
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