GABA action in immature neocortical neurons directly depends on the availability of ketone bodies.
In the early postnatal period, energy metabolism in the suckling rodent brain relies to a large extent on metabolic pathways alternate to glucose such as the utilization of ketone bodies (KBs). However, how KBs affect neuronal excitability is not known. Using recordings of single NMDA and GABA-activated channels in neocortical pyramidal cells we studied the effects of KBs on the resting membrane potential (E(m)) and reversal potential of GABA-induced anionic currents (E(GABA)), respectively. We show that during postnatal development (P3-P19) if neocortical brain slices are adequately supplied with KBs, E(m) and E(GABA) are both maintained at negative levels of about -83 and -80 mV, respectively. Conversely, a KB deficiency causes a significant depolarization of both E(m) (>5 mV) and E(GABA) (>15 mV). The KB-mediated shift in E(GABA) is largely determined by the interaction of the NKCC1 cotransporter and Cl(-)/HCO3 transporter(s). Therefore, by inducing a hyperpolarizing shift in E(m) and modulating GABA signaling mode, KBs can efficiently control the excitability of neonatal cortical neurons.
Rheims
Sylvain
S
INMED-INSERM U901, Université de la Méditerranée, Marseille, France.
Holmgren
Carl D
CD
Chazal
Genevieve
G
Mulder
Jan
J
Harkany
Tibor
T
Zilberter
Tanya
T
Zilberter
Yuri
Y
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007657:Ketone Bodies / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D028021:Sodium-Potassium-Chloride Symporters / Q000187:drug effects / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D027963:Chloride-Bicarbonate Antiporters; D007657:Ketone Bodies; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D005680:gamma-Aminobutyric Acid