BAD-dependent regulation of fuel metabolism and K(ATP) channel activity confers resistance to epileptic seizures

Neuron. 2012 May 24;74(4):719-30. doi: 10.1016/j.neuron.2012.03.032.


Neuronal excitation can be substantially modulated by alterations in metabolism, as evident from the anticonvulsant effect of diets that reduce glucose utilization and promote ketone body metabolism. We provide genetic evidence that BAD, a protein with dual functions in apoptosis and glucose metabolism, imparts reciprocal effects on metabolism of glucose and ketone bodies in brain cells. These effects involve phosphoregulation of BAD and are independent of its apoptotic function. BAD modifications that reduce glucose metabolism produce a marked increase in the activity of metabolically sensitive K(ATP) channels in neurons, as well as resistance to behavioral and electrographic seizures in vivo. Seizure resistance is reversed by genetic ablation of the K(ATP) channel, implicating the BAD-K(ATP) axis in metabolic control of neuronal excitation and seizure responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Astrocytes / metabolism
  • Cells, Cultured
  • Electroencephalography
  • Energy Metabolism / physiology*
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • KATP Channels / metabolism*
  • Mice
  • Mice, Transgenic
  • Neurons / metabolism
  • Oxygen Consumption / physiology
  • Phosphorylation
  • Seizures / chemically induced
  • Seizures / metabolism*
  • Seizures / physiopathology
  • bcl-Associated Death Protein / genetics
  • bcl-Associated Death Protein / metabolism*


  • KATP Channels
  • bcl-Associated Death Protein