Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Membrane / drug effects
-
Cell Membrane / metabolism
-
Cerebral Cortex / cytology
-
Cerebral Cortex / growth & development*
-
Cerebral Cortex / metabolism*
-
Chloride-Bicarbonate Antiporters / drug effects
-
Chloride-Bicarbonate Antiporters / metabolism
-
Energy Metabolism / drug effects
-
Energy Metabolism / physiology*
-
Female
-
Ketone Bodies / metabolism*
-
Ketone Bodies / pharmacology
-
Male
-
Membrane Potentials / drug effects
-
Membrane Potentials / physiology
-
Mice
-
Neural Inhibition / drug effects
-
Neural Inhibition / physiology
-
Neurons / drug effects
-
Neurons / metabolism*
-
Organ Culture Techniques
-
Patch-Clamp Techniques
-
Receptors, GABA / drug effects
-
Receptors, GABA / metabolism
-
Receptors, N-Methyl-D-Aspartate / drug effects
-
Receptors, N-Methyl-D-Aspartate / metabolism
-
Signal Transduction / drug effects
-
Signal Transduction / physiology
-
Sodium-Potassium-Chloride Symporters / drug effects
-
Sodium-Potassium-Chloride Symporters / metabolism
-
Solute Carrier Family 12, Member 2
-
gamma-Aminobutyric Acid / metabolism*
-
gamma-Aminobutyric Acid / pharmacology
Substances
-
Chloride-Bicarbonate Antiporters
-
Ketone Bodies
-
Receptors, GABA
-
Receptors, N-Methyl-D-Aspartate
-
Slc12a2 protein, mouse
-
Sodium-Potassium-Chloride Symporters
-
Solute Carrier Family 12, Member 2
-
gamma-Aminobutyric Acid